Biotechnology Forums

As future of biotechnology sector seems to be bright and further with more advancement of technology it seems to be easier to become an investor in the sector of biotechnology. Investment is a process of earning money with patience. The growth in the sector of Biotechnology and other biological business had proved their metal in past and therefore can be a good opportunity which is called as Bio-business. Bio-business is emerging sector and in simple words it is a combination of investment in biological sectors and earning by serving the peoples using today’s biological science.

It is expected by 2015 that the global biotechnology business will grow over $320 billion. Market development is stimulated by improved R&D financing, federal government initiatives, economic healing and biotechnology utilized in agriculture, industrial and medical sciences. Developing nations, especially China and India, are coming to be major markets in the industries of agricultural and commercial biotechnology. Also there is ample opportunity in other such developing countries’. To invest in Biotechnology is not simple thing for a newbie and therefore it can be achieved by gaining the knowledge and information of this sector.

Biotechnology is a complex producer industry supplying the necessary technology and methods required by other industries to develop products that increase value for Doctors , other suppliers, consumers and end customer. The biotechnology industry consists of large multinational firms, public firms, entrepreneurial firms and private research entities. The academia, the bio informatics and dedicated biotechnology companies are investing their money to grow their business. The success is achieved through the performance and by proving quality and quantity supply. The growth is achieved in this way and over the period of time. The investment in such organization can be a success. Therefore for us to invest, we need to have fundamental and technical aspects of any organization before going for it. Biotechnology is one part of a multifaceted business model. In such models, firms in the global biotechnology industry range from small firms to R&Ds with sophisticated base business facilities.

Growing is an increasing trend while developed is a achieved stage. The one who can consistently perform at this stage only sustains the competitive world of business. Therefore one should invest in this sector only when the growth trend is consistent. This is also true that one can opt for biotechnology as compared to other sectors as “The first century of coming millennium will not only belong to IT and communications technology, as we often believe, but also to biotechnology, and its immense potential to contribute to mankind and animal health, farming, diary production, manufacturing and sustainable development. The biotechnology based medical science will be the leader among all for next few decades. “
So, one can become an invertors easily with the growing business and also can easily get involve in Biotechnology industries ETFs, stocks or other worldly biotechnology indices (At their own risk).

So,Knowing ETFs,stocks and biotechnological indices is very important .It will get easier to know as you start get involving in this kinds of investments. Keeping track of all these will increase your experience and as results you can plan in investing systematically. But it is subjected to fundamental and analytical strengths of all that is involved.

ETFs are Exchange Traded Funds – Buying Selling and trading ETFs.ETFs are mini-portfolio which track assets like index or commodities.Advantages of ETF’s over mutual fund – There is no multiple transaction but only one trade one price that is single transaction, Cost effectiveness-That is they have less commissions, reduced tax bill, easy to trade , traded throughout market hours, transparency that is daily basis lists of assets publication. This is simple and easy to understand.
Now you can start utilizing Biotechnology ETFs in your trading portfolio or investment stratergy and focusing on biotechnology equities.
Here is the list of Some of the biotechnology funds (for your information) -
BBH-Market vector Biotech ETF
BBI –Ultra NASDAQ Biotechnology ETF
BIS-Ultrashort NASDAQ Biotechnology ETF
FBT-First Trust NYSE Arca Biotech Index ETF
IBB-iShares Nasdaq Biotechnology ETF
PBE-Powershares Dynamic Biotech & Genome ETF
XBI-SPDR S&P Biotech ETF

This is article is only informative and for educational purpose.

Thanks to this forum which helps us to learn and exchange our view; not only on science but also on its applications for our wellbeing;
Bio-business- Investing in Biotechnology! Idea

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Many diseases (if not all) are a direct consequence of infection by some pathogenic organism (especially bacteria). Having read and known the very efficient and complicated immune systems of human beings; and especially having read about the existence of various broad-spectrum antibiotics, one must be curious to know the mechanism by which certain (most these days) bacteria become superbugs/multi-drug resistant/host immune invaders? This article is aimed at addressing most of these questions.

Mechanism(s) of Host Immune Resistance:

For any microbe to infect human body, it has to encounter and overcome upto 3 levels of human immune defense: (i). Surface Barriers (Skin, Mucus, Enzymes) which forbid the attachment of the microbe to the host (ii) Once the surface barriers are overcome, Non-Specific Resistance (innate immunity of humans) which offers resistance to all foreign microbes/antigens irrespective of their nature. It is contributed by complement system, cytokines, anti-body complexes and WBCs etc. (iii). If somehow, a bacteria penetrates the innate immunity too, it's confronted with 3rd level (or second line of defence, after surface barriers) called Specific Resistance (or Acquired Immunity). It is contributed by Memory T/B cells and antibodies produced in response to the specific bacteria/antigen.

Considering such a concerted immune system, it's quite intriguing to know the ways by which bacteria penetrate such defense measures. Following is a brief on the same:
Though the entry is possible through respiratory/food/blood route, where the 1st level cannot do much if the microbial load is very high, it comes to the role of 1st Line and 2nd Line of Defense to decide the fate.

Complement Evasion:
Presence of capsulated cell wall/membrane is the most common way of evading complement response. For e.g Neisseria gonorrhoeae has the capability to generate modified surface lipopolysaccharides to prevent MAC (membrane attack complex) formation.

Phagocytosis Evasion

Formation of a mucous layer on the surface by bacteria helps them evade contact by phagocytes (contact with the antigen/bacteria is cruacial for phagocytosis), thus evading the elimination. For e.g Haemophilus influenzae does so the same way.

Some bacteria can even produce leukocidins (phagocyte killing agents). For e.g Staphylococcus sp. does so the same way.

Even there are some which can rather survive inside the phagocytes! Mycobacterium tuberculosis, Listeria monocytogenes, Rickettsia.

Specific Immune Response Evasion

Again, generation of non-antigenic capsules (like Streptococcus pyogenes), or some smart moves like genetic variations in pili so that antibodies don't get specific (like Neisseria gonorrhoeae) or production of proteases that can lyse the antibodies! (like synthesis of IgA proteases by Neisseria gonorrhoeae) etc are some of the common ways of evading specific immune response.

Mechanism(s) of Antimicrobial Resistance

Emergence of MDR Strains (Multi-drug-resistant) starins of various pathogenic bacteria is quite common these days. Here's a look at what systems they develop to evade various broad-spectrum antibiotics:

(i). Inhibition of Drug Penetration

Development of special envelopes that are impermeable to drugs is one of common mechanisms of drug resistance. E.g Mycobacteria have high content of mycolic acids in the lipid layer of peptidoglycan (cell wall) which makes it impermeable to most drugs.

(ii). Efflux Pumps
Another mode of drug resistance is development of efflux pumps in the plasma membrane that can pump the drug out of the cell even if it enters successfully! E.g Mycobacterium smegmatis, Staphylococcus aureus etc

(iii). Chemical Modification]
Another mechanism recently found is of inactivating the drug by chemically modifying it's structure! Phosphorylation, glycosylation, acetylation of drugs can render them inactivated. For. eg most penicillin resistant bacteria synthesize penicillinase to hydrolyse beta-lactum ring of penicillins, making them inactive.

(iv). Alternative routes

Some drugs target a product synthesis route in bacteria and inhibit their development. Such bacteria develop resistance by either switching to pre-formed product in the surrounding/host or by increasing the rate of production. For. e.g sulfonamides inhibit folic acid synthesis in bacteria, and they develop resistance by simply using host folic acid!

So, nowadays, bacteria are becoming broad-spectrum in the mechanisms of inhibiting the affect of drugs/host immune system. This is indeed alarming, and needs concerted efforts of researchers across the world to de-code the mode of evasion, rather than just focusing on discovering new forms of anti-biotics.

Hope this article gave an insight to the aspects targeted.

Suggested Reading(s):

http://crohn.ie/archive/primer/imunevad.htm

Prescott's Microbiology (5th edition)

Thanks!

Unity is strength, they say.

This is also true in bacterial pathogenesis. Recent researches reveal that many pathogenic bacteria have communication networks that let them know when their numbers are sufficient to overwhelm host defenses. The theory is simple: if they began the assault with an army too small, the host can easily kill them. But if there are enough fighters, they can defeat the host. Their strategy is to multiply within the host without causing damage, until a sufficient cell number is reached. When the population is adequate to overcome host defense systems, they become violent.

So, how do these single celled creatures actually ‘talk’ with each other?

It is found that bacterial cell-to-cell communication occurs via low molecular weight diffusible organic molecules referred to as autoinducers (AIs). These AIs diffuse away at low cell densities and, therefore, are present at concentrations below the level required for detection. With the cell density, increases the concentrations of AIs. Upon reaching a critical concentration, the AIs bind to and stimulate receptors inside bacterial cells. These receptors then activate the transcription of genes necessary for bacterial virulence, such as the genes regulating the production of virulence factors, formation of biofilms, antibiotic resistance etc. This process is known as autoinduction. Since this process is activated after a critical population density, or quorum, is reached, it is also termed as Quorum Sensing (QS).

Different bacterial species use different languages, i.e. different classes of signalling molecules. Furthermore, single bacterial species may have more than one QS system and therefore can use more than one signal molecule. Gram negative bacteria primarily use acyl-homoserine lactones (AHLs) as their signalling molecules while Gram-positive bacteria use peptides, called autoinducing peptides (AIPs). Some groups of AIs are known to function as interspecies and interkingdom communication networks.

Many clinically-important bacteria use QS to regulate their virulence.

Therefore, scientists have been studying in detail, the role of quorum sensing in the virulence of many human pathogens. QS is found to regulate genes involved in virulence, biofilm architecture and antibiotic resistance in these bacteria, thus playing a vital role during the infections by these pathogens.

One such culprit is Staphylococcus aureus, a member of the normal flora, which can be a dangerous opportunistic pathogen causing infections leading to pneumonia, bacteremia, and sepsis. Moreover, they form biofilms on clinical surfaces, thus accounting for many hospital related infections. S. aureus infections are difficult to eliminate due to their resistance to many antibiotics.

Pseudomonas aerogenosa is another opportunistic pathogen which produces both acute and chronic diseases in humans. It is responsible for severe respiratory infections such as chronic lung infection in cystic fibrosis patients. P. aerogenosa is also associated with nosocomial infections. They have the ability of forming complex biofilms which are highly resistant to antibiotics.

The role of quorum sensing in the virulence of Escherichia coli has also been demonstrated. QS controls the expression of genes regulating the functions such as flagellar motility, surface adhesion and Shiga toxin production which are involved in the pathogenicity of Enterohaemorrhagic E. coli (EHEC) and Enteropathogenic E. coli (EPEC).

Among other pathogenic bacteria that employ QS in their virulence are Bacillus cereus, Salmonella typhimurium and Vibrio cholerae.

Keep them in the dark.

And you can control them, scientists suggest. The idea is to block their communication systems and keep the bacteria from knowing that the optimal population density has reached. This will prevent the transition from inert mode to the virulent mode.

The researchers believe that this strategy would not cause antibiotic resistance in bacteria because it doesn’t aim to kill the cells. When a community of bacteria is treated with traditional antibiotics, a few resistant mutants within the population will survive. Proliferation and further mutation of these survivors will result in antibiotic resistant populations. On the contrary, blocking their QS system will merely keep them in a non-aggressive form, thus allowing the immune system of the body to combat the bacteria.

Quorum Sensing Inhibitors: the new wonder drug?

One of the most successful mechanisms of blocking QS is through competitive inhibitors which are structural analogues of the primary autoinducers produced by bacteria. These inhibitors bind to the regulatory regions of the virulent genes, thereby preventing the binding of bacterial AIs. This inhibits the activation those genes, thus disabling the expression of virulence and giving enough time for the host defense system to combat bacteria.

Efforts have been made to discover such inhibitors with the goal of designing novel antimicrobial therapeutics. Natural quorum sensing inhibitors identified thus far include cyclic sulphur compounds, halogenated furanones, patulin and penicillin acid. Garlic extract was also considered to be a potential QS inhibitor.

Scientists report based on in-vitro studies, that bacteria do not seem to develop resistance to these inhibitors. In one study, when V. cholerae bacteria were grown in the presence of a large excess of such inhibitors, resistance could not be observed even after 26 subsequent generations.

There is hope that this could be the new wonder drug for conquering antibiotic resistant infections.

For further reference:

Antunes, L.C.M., Ferreira, R.B. R., Buckner, M.M. C., Finlay, B.B. (2010) Quorum sensing in bacterial virulence, Microbiology,156, 2271–2282.

Rutherford, S. T., Bassler, B. L. (2012). Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control. Cold Spring Harbor perspectives in medicine, 2(11).

Reading, N. C., & Sperandio, V. (2006). Quorum sensing: the many languages of bacteria. FEMS microbiology letters, 254(1), 1-11.

The intentionally developed toxins/pathogens of biological origin with an aim to harm the target hosts (normally humans), by disrupting their biological processes, are called Biohazard weapons or simply Bioweapons.

Biohazard Alert Symbol

What encourages the use of bioweapons is:

a. Ease of producing the pathogenic microbes
b. Low cost of production
c. Stealth granted in terms of portability, which cannot be achieved in porting bulky explosives.
d. Transmission of weapon effect (a single target population can infect other healthy populations). Just imagine an epidemic/pandemic weapon!

Considering such advantages of biological weapons, the anti-social elements have worked pillar to post in extracting utility out of these nature-inspired tools of destruction, which has rather raised the alarms among nations to initiate/back-up defense response to such probable activities, through biotechnological research.

This article will take you through historical developments/advances in Bioweapons.

Plague-the most sought after and historical choice:

The reportedly first ever use of a biological weapons goes back to 14th Century War of Kaffa, when Mongolian Army dispersed heaps of plague infected cadavers into the city resulting a mass spread of the black death (which didn't spare the mongols either!). With the knowledge obtained about the disease's epidemiology, recognizing Yersinia pestis bacteria as the causative agent, the probability of it's use as a weapon peaked up, which was manifested in World War II, when Japan initiated multiple attacks of plague infected fleas on Chinese cities through air-crafts! A rather shocker came through the publication of Davis CJ's "Nuclear Blindness: an overview of the biological weapons programs of the former Soviet Union and Iraq" which mentioned Soviets' backed-up intercontinental ballistic missile warheads loaded with plague bacilli for launch before 1985! Such instances indeed put Plague on high-risk bioweapon list.

Small-pox: Another Obnoxious Weapon
1763's distribution of infected blankets and handkerchiefs by British army to Native Americans in Pontiac Rebellion, causing a lot of deaths, is reported as one of the earliest instances of use of small-pox as a bioweapon. Unlike plague, small pox is strictly human-specific weapon. The causative agent is Virus-Variola major or Variola minor the access to which is almost eradicated since 1970s. The only threat that remains is in the form of aerosols of the infected fluids that may spread the disease.

Anthrax in WWI

The report submitted by George W. Merck,biological-warfare adviser to President Roosevelt, in 1943 about the German Soldiers's action of inoculating horses and cattle with anthrax to cause the deadly disease in the indispensable animals of those times during WWI in France and Bucharest, raised the alarm among the nations about the seriousness of this weapon, which can easily be spread even in powder forms (instances of letters loaded with anthrax are also there). Adding gravity to the lethal effect, anthrax spores are highly persistent and may survive for decades even after chemical cleansing!

9 out of 10 victims die if spores enter the lungs and hardly 1 in 10 survive even after anti-biotic doses! But the disease is not transmitted from one infected person to other and the exposure has to be to the spores for the disease to effect. The causative agent is the spore forming Bacillus anthracis

The Biological Weapon Convention (BWC), 1972

The 1925 Geneva Protocol (came into being after reported uses of Bioweapons in WWI) asked for ban of use of any bioweapon (but not possession of it). Evidently, it wasn't abided by all, as in WWII Japan attacked China with Plague fleas! With an aim to strengthen the Geneva protocol, international community came-up with the BWC in 1972, for banning the production & possession of any kind of bioweapon held with an intention to harm the civil life.Though it came into force in 1975 with about 20 countries signing the treaty, and currently being over 180 countries a part it, there hardly exists any protocol to verify the authenticity of the signed claims of the members.

The threat of use and secret possession (as it came forward in case of the soviet union) always remains!

Bioweapon Defense
Considering the always hanging sword of Bioweapons, Nations are working round the clock for R&D of swift response to nullify the bioweapon attacks. A few of the defense actions are enlisted below:

1. Development of Prophylactic Vaccines
2. Therapeutic cocktails consisting of antibiotics, antiviral drugs, and antibodies for passive protection
3. Biodetectors/Biosensors/Indicators of suspicious activity/agents.
4. Strengthening innate immunity of the targets through injection of activators of innate immunity for short periods right after the attack.
5. Protective measures for food crops, which are at equal vulnerability of attack.

Recently, the extraction of small pox protein that causes the same pathogenic response as the virus itself has further raised the doubts over it's use in spreading the disease. The field of transgenics has elevated the concerns to next levels. Though the need for international surveillance of bioweapons' development was always felt, no strict action has been taken to realize the terms of the disarmament treaty of BWC. The concept of Bioweapons was taken to a next level when an "anonymous" country encouraged the emigration of HIV infected sex-workers to it's neighboring country. Such cases only highlight the gravity of problem being faced by world at large, which in immediate future might take even serious turns, unless some ethical norms are set in every Nation, apart from the much needed strict actions of the UN in enforcing BWC among the members and non-members.

Documentary by NatGeo on Bioweapons:

Metabolomics is an emerging research method in life sciences that takes the approach of quantifying and analysing all metabolites in a given sample. Changes as low as one I a few thousand can be detected using this method, utilizing powerful analytic devices and chemometric software. It is rapidly becoming a useful tool used in conjunction with other systems biology methods to provide medically relevant results. The metabolome represents the collection of all metabolites in a biological unit, i.e. a cell, tissue, organ or organism, which represent the end products of cellular processes. Thus, while mRNA gene expression data and proteomic analyses do not provide the whole picture of what might be happening in a cell, metabolic profiling can give an instantaneous picture of the current physiology of that cell. One of the main challenges of systems biology today is to integrate proteomic, transcriptomic, and metabolomic information to give a more complete picture of living organisms.

According to metabolomics researchers, further development of metabolimics platforms and tools will at one point allow for the creation of extremely fast and comprehensive medical tests requiring only a fraction of samples current analytical and diagnostic tools require. Many new ideas and potential uses were discussed at OMICS group’s “Metabolomics and Systems Biology” conference in April.
“Interpretations of metabolomics signatures will make rapid bedside diagnostics possible. In 5–10 years this information will transform our diagnostic capabilities. The meaningful metabolome interpretation will be available to a physician within minutes for a fraction of the cost of today’s analyses.” - said Chris Beecher, Ph.D., CSO, from NextGen Metabolomics.

The company NextGen is contributing to this vision by working on Isotopic Ratio Outlier Analysis™ (IROA), a mass-spectrometry-based protocol that enables efficient identification of all biological metabolites in a sample and their relative concentration.

This technology is based on a physiochemical phenomenon of naturally occurring C13 atoms. C13 has an extra neutron producing a pattern of additional peaks for each given metabolite in a sample. Because of their relatively low and uncommon natural abundance and the presence of other interfering elemental isotopes, these additional peaks (called M+1, M+2, etc.) are very small and not very informative.
“We simply boosted the C13 concentration by growing cells in a culture media engineered with precise balances of C13-bearing components, when you compare a culture grown with 5% C13 with culture grown in 95% C13, each metabolite will be represented by a symmetrical pattern of C12 and C13 peaks. The parameters of this pattern tell us how many carbons the molecule contains and it’s mass.”, as doctor Beecher explained.

The mirror symmetry of MS peaks in IROA experiments enables fast classification and identification of all peaks as real cell products (those that have have mirror counterparts) or artifacts and contaminants (no enhanced M+1, M+2, etc.). NextGen computer algorithms look for the same symmetry to perform phenotyping experiments.

To identify specific metabolites in tissue biopsies, the tissue cells are mixed and analyzed together with “standard” cells that were isotopicaly labelled with IROA C13 media. The tissue-derived metabolites can be easily identified by their mass and position relative to the standard using this method.

The company’s method has already given a significant proof of principle in the area of toxicology, concerning analysis of drug candidates. The team under Dr. Beecher used IROA to show the effects and response of every metabolite in the cell to flucytosine, a well-characterized inhibitor of DNA synthesis. The data showed clear response in metabolic pathways related to nucleotide biosynthesis, but not in other pathways, confirming the accuracy of the approach.

“We plan to perfect this technology to answer fundamental questions in drug development. What toxicities should we expect? What is the biological reason for this toxicity?”
NextGen plans to set up internal biomarker and toxicology discovery departments based on IROA technology.

Researchers at Georgetown University Medical Center plan to start a clinical trial with humans, furthering their finding related to applying small doses of a leukemia drug to mice brains. These small doses showed a possible ability to halt development of neurodegenerative disorders.
This study offers a unique and exciting new strategy to treat neurodegenerative diseases that develop due to abnormal buildups of proteins like Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington disease and Lewy body dementia, and many others.

"This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain," stated the study's senior investigator, neuroscientist Charbel E-H Moussa, MB, PhD who heads the laboratory of dementia and Parkinsonism at Georgetown.

When the drug, nilotinib, is used to treat chronic myelogenous leukemia (CML), it forces cancer cells into autophagy, a biological process that leads the cells to essentially devour itself, whicj in turn leads to death of tumor cells in cancer.

"The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death," Moussa says. "We reasoned that small doses for these mice, an equivalent to one percent of the dose used in humans -- would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else."

Moussa has, for a while now, been working on a way to forcefully activate the self-meitenance mechanism of neurons, and force them to clean up their internal damaged and dysfunctional proteins, their ‘garbage’, and he came up with the idea of using cancer drugs that push autophagy, a version of internal clean-up, in tumors to help diseased brains.

"No one has tried anything like this before," he says.
Moussa, and his two co-authors -- graduate student Michaeline Hebron and Irina Lonskaya, PhD, a postdoctoral researcher in Moussa's lab searched for cancer drugs that can specifically cross the blood-brain barrier. They discovered two plausible candidates; nilotinib and bosutinib, which is also approved and used to treat CML. This study discusses experiments with nilotinib, but Moussa says that use of bosutinib is also beneficial.

The mice used for this experiment have been shown to over-express alpha-Synuclein, the very same protein that builds up in Lewy bodies in Parkinson's disease and dementia patients and which is found in many other neurodegenerative diseases in the form of intracellular protein buildup. The animals were given one milligram of nilotinib every two days, a dose much lower that the FDA approved dose for treting cancer, of up to 1,000 milligrams of nilotinib once a day for CML patients.
"We successfully tested this for several diseases models that have an accumulation of intracellular protein. It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson's disease as well as Lewy body dementia." – says Moussa.

After applying the cancer drug and noting the cellular results the scientist also noted a markable increase in mobility and functionality for the mice, apparently reducing the symptoms of the neurodegenerative diseases.

Moussa hypothesizes that for the therapy to be most efficient, it would have to be applied early in the development of the neurodegenerative disorders, to initially prevent the harmful buildup of protein and prevent any serious damage from occurring to neurons. Using this therapy later in the disease progression may retard further extracellular plaque formation and accumulation of intracellular proteins in inclusions such as Lewy bodies.

Moussa is planning a phase II clinical trial in participants who have been diagnosed with disorders that feature build-up of alpha Synuclein, including Lewy body dementia, Parkinson's disease, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).

Results published online May 10 in Human Molecular Genetics

University of Arizona, a research team working on neurons treated with statin has made a new discovery; unusual ball-like swellings within neurons, which the team has termed the "beads-on-a-string" effect.
The team is not yet entirely sure why the beads form. However, the team believes that further investigation of the beads will help inform why some people experience cognitive declines while taking statins, a wide-spread class of cholesterol reducing drugs.

"What we think we've found is a laboratory demonstration of a problem in the neuron that is a more severe version for what is happening in some peoples' brains when they take statins," said Restifo, a UA professor of neuroscience, neurology and cellular and molecular medicine, and principal investigator on the project.

Restifo and her team's co-authored study and findings were published in Disease Models & Mechanisms. Robert Kraft, a former research associate in the department of neuroscience, is lead author on the article.
Restifo and Kraft cite data collected from clinical studies of patients, which refers to patients being told by their physicians that the negative cognitive effects experienced after taking statins are age-related symptoms. However, the research teams new findings imply that the neurodegenerative effects experienced by the patients are a result of the neurons negative reaction to statin.

After concluding that the likely culprit for this is statin, the team found that removing statins results in a disappearance of the beads-on-a-string, and also a restoration of normal neural growth. In further research the UA team intends to investigate how genetics may be involved in the bead formation to determine how hypersensitivity to the drugs can occur in some people. Team members believe that genetic differences could involve neurons directly, or the statin interaction with the blood-brain barrier.

"This is a great first step on the road toward more personalized medication and therapy. If we can figure out a way to identify patients who will have certain side effects, we can improve therapeutic outcomes." said David M. Labiner, who heads the UA department of neurology.

The research team has many external fundings and grants pending, and they hope to further their research to inform the doctors and patients of potential hazards and complications using this drug.

"If we are able to do genetic studies, the goal will be to come up with a predictive test so that a patient with high cholesterol could be tested first to determine whether they have sensitivity to statins," Restifo said.
Restifo uses an analogy with traffic to illustrate her teams findings.
The beads represent a sort of traffic jam, she described. In the presence of statins, neurons undergo a "dramatic change in their morphology,"
"Those very, very dramatic and obvious swellings are inside the neurons and act like a traffic pileup that is so bad that it disrupts the function of the neurons," she said.

Kraft's observations led to team's novel discovery. Restifo, Kraft and their colleagues had long been investigating mutations in genes, largely for the benefit of advancing discoveries toward the improved treatment of autism and other cognitive disorders. A stumbling led them to take another direction in their research, focusing on the apparent effect of statin.
The team tested over a thousand blind-selected drug components on fruit fly neurons, testing for possible mutating effects. Then Kraft observed that one compound, then another and then two more all created the same reaction "these bulges, which we called beads-on-a-string,'" Kraft said. "And they were the only drugs causing this effect."

"There is no question that these are very important and very useful drugs," Restifo said. Statins are used worldwide to lower cholesterol and prevent blood clots, heart attacks and strokes.
But too much remains unknown about how the drugs' effects may contribute to muscular, cognitive and behavioral changes.
"We don't know the implications of the beads, but we have a number of hypotheses to test," Restifo said, hoping that further research by her team will help to better understand what exactly happens when the transportation systems in neurons are compromised.

"If statins have an effect on how the nervous system matures, that could be devastating. Memory loss or any sort of disruption of your memory and cognition can have quite severe effects and negative consequences.” Kraft said.

R. Kraft, A. Kahn, J. L. Medina-Franco, M. L. Orlowski, C. Baynes, F. Lopez-Vallejo, K. Barnard, G. M. Maggiora, L. L. Restifo. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions. Disease Models & Mechanisms, 2012;

Have you ever wondered what makes the gecko lizard stroll over practically any surface--be it a ceiling/floor/wall? Have you ever imagined a situation where soldiers at the war-front could instantly treat their wounds/slits on their own?

Well, the two questions might seem distantly related, but this article will show you how these two questions enabled the invention of two brilliant nano-scale bandage products, by scientists working relentlessly on these quests, sitting in the elite MIT.

Instant Healing Physical Nano-Scale Bandage

When the scholars of Institute of Soldier Nanotechnologies, MIT imagined about a bandage which could instantly heal the soldiers with severe physical injuries in battles, they came up with a product extra-ordinare--a thrombin-coated nanobandage! Leader of this research funded by Institute of Soldier Nanotechnologies and a Denmark-based company, Ferrosan Medical Devices was Paula Hammond. The use of thrombin may be explained by the obvious fact that it's a natural clotting agent found in blood. But, preparing it in a solution, along with tannic acid, and then spraying it using a nano-sprayer on gauge sponges made it a brilliant bandage, that could heal in seconds! The mixture was highly stable on the sponge which could be carried to open areas with no fear of degradation; and the nano-spray made sure that the effective area of absorption by sponge is very high, and the area of action of thrombin is also very High!

The idea of nano-spraying was inspired by the conventional practice of using gelatin sponges to stop bleeding in hospitals. The sponges were dipped in liquid thrombin just before application and was thus used to halt the profuse bleeding. The limitations were obvious: the current system couldn't be taken to a battle field and application on all parts of the body is not effective. Pre-coating of gelatin sponges with layers of nano-spray of thrombin/tannic acid, made it a highly stable and portable system ( not just for doctors, but for soldiers themselves too!). Animal tests revealed that nano-bandage could stop a physical injury in just 60 seconds, while a normal dipped bandage took 150 seconds, and even a 12 min application couldn't help stop the bleeding when just the gauge was used. The scientific group has taken the next steps by using a spray of a mixture of thrombin-tannic acid-vancomycin (anti-biotic) for the obvious reasons of avoiding any microbial infection too!

Following is a highly informative Podcast on Dr. Paula Hammond's research:

Super-Effective Internal Nano-Bandage

Another challenge that MITians (rather MIT + Harvard) had in mind was-effective and instant sealing of internal injuries/slits during surgeries, which were too big for sutures to accommodate. Like covering up of the diseased intestinal segment surgically removed or an injury on a sensitive tissue like cardiac tissue and other surgical wounds, were what MITians targeting. The scientific team on this pursuit was led by MIT Prof. Robert Langer and Jeff Karp, an instructor of medicine at Brigham and Women's Hospital and Harvard Medical School.
The biggest challenge in developing a bandage alternative to sutures was that they had to work on a glueing mechanism which could help stick the bandage to as wet surfaces as internal tissues of the body, and still be flexible, biocompatible and degradable.

And, the solution was observed in gecko lizard! Gecko's feet have nano-scale hills & valleys that enable it to cling to walls/ceilings. Taking inspiration from it, the bandage surface was patterned with similar nano-scale hills and valleys, followed by a thin layer of gecko's pad like glue. The combination of patterned surface and gecko like glue, made sure of a substance that could stick to wet surfaces like internal tissues/organs.
The material of the surface was Karp's self developed biorubber and the patterning was done using micropatterning technology (same as used for microchips). Trials were done on pig's tissues with exceptional results. Such a bandage can be loaded with drugs/antibiotics/anti-clotters etc and it's binding capacity can be maneuvered with by changing the micropattern. So, it provides huge flexibility over the use of the bandage.

Following is a video on MIT News Update by Jeffery Karp on the new Medical Adhesive:

The targeted approach of MIT scientists in addressing two extremely significant issues of finding quick healing solution to physical and internal injuries in critical situations like warfare and vital organ surgeries, really set an example for others to follow for the welfare of society at large. These inventions will really change the face of surgeries and their efficacy.

Thanks!

Stem cells are the basic building blocks for many types of cells in the body. Despite the big therapeutic potential for stem cells to treat serious disorders, there are still concerns about potentially dangerous results. Researchers are excited about the possibilities of saving lives and reducing morbidity from disease, but there are also fears regarding unexpected results and effects from stem cell usage. With recent technologies the concept of stem cell therapies is no longer such a foreign one. The benefits of stem cell therapies are enormous, but risks must also be considered.

Embryonic Stem Cells

Main concern with embryonic stem cells is related to uncontrolled growth. Embryonic stem cells are cells which tend to grow fast. However, the rapidly growth must be carefully guided by researchers. These stem cells need to be cultivated and directed into specialised cells with great care because the potential for remaining stem cells to grow uncontrolled could be terrible. These uncontrolled stem cells could eventually form tumours. Embryonic stem cells division are subject to errors during cell division that can result in abnormal chromosome forms. Cytogenetics, the study of abnormal chromosomes, has shown that stem cells tend to show the chromosome aberrations. The most frequent change in human embryonic stem cells involves gain of chromosomes 12 or 17, which both are associated with cancer. There is no way to differentiate embryonic stem cells with abnormal chromosomes form and normal stem cells without genetic testing, because both express the same proteins and specifically stem cell markers. Additionally, the presence of chromosome changes does not affect the ability of these cells to different into appropriate cell types. However, most of these divisions lead to cell death, as a result accidents in division, which lead to extra or missing chromosomes.
Some researchers claim normal chromosomes in human embryonic cells after prolonged time in culture, even after 100 passages. Others have reported recurrent aberrations involving chromosomes 12 and 17 occurring between passages 25 and 45. Despite optimal culture techniques, the genetic integrity of embryonic stem cells is difficult to keep, because of the stresses of tissue culture and the other pressures exerted on the cells after cultures have been frozen and thawed. Cryopreserved embryonic stem cells tend to grow poorly after thawing. Some cells with a growth rate resulting from an extra chromosome 12 or 17 can increase in number and eventually overgrow the normal cells.

Adult Stem Cells

Unlike embryonic stem cells, which can give rise to any lineage, adult stem cells can only generate cells of a specific lineage. Adult stem cells are present in specialized tissues throughout the body, such as bone marrow or skin, and are capable of unlimited production of differentiated cells. For adult stem cells to be able to divide continuously, they must have an active telomerase gene, which is characteristic of all embryonic stem cells. The presence of the telomerase gene enables stem cells to maintain the integrity of the chromosomes throughout many cell divisions, whereas differentiated cells of the body do not have this gene and therefore can undergo only a limited number of divisions. There is a general belief that cancer cells derive from mutated adult stem cells because differentiated cells have a limited life-span and therefore cannot accumulate the necessary mutations for malignant transformation.

Most mutations in adult stem cells that give rise to cancer or leukemia tend to be lineage specific because certain changes will promote growth in one tissue, but not another. Chronic myeloid leukemia is example. Chronic myeloid leukemia is caused by specific chromosome mutations in a bone marrow stem cell. The normal stem cells in the bone marrow divide only when more blood cells are needed, and they become quiet as a result of continuous blood cell production by the mutated stem cells. This enables the abnormal stem cells populating the bone marrow to divide continuously. The mutation in chronic myeloid leukemia includes specific mutations between chromosomes 9 and 22, but this chromosome aberration has no effect in any other tissue because chromosome changes associated with cancer are lineage specific.

The fact that cultured adult stem cells can undergo tissue-specific chromosome changes associated with malignant diseases emphasizes the need to ensure that any adult stem cells used therapeutically, including reprogrammed cells, be monitored for genetic changes.

Examples

Scientists have tried embryonic stem cell transplantation in animal experimental models for stroke. Undifferentiated embryonic stem cells that were transplanted into the rat brain, migrated to the damaged area and differentiated into neurons along the border of the lesion. When the same cell line was transplanted into the mouse brain, the embryonic cells did not migrate but remained in one area to produce malignant carcinomas. Embryonic stem cells were undifferentiated or pre-differentiated in vitro to neural progenitor cells.

Mouse embryonic stem cells can differentiate into liver cells in culture. When mice were injected in the spleen with 9 day old cultures, the cells migrated to the liver and generated liver cells. However, when 9 day old and 15 day old cell cultures were injected directly into the mouse liver, there was a high incidence of tumor formation. The authors conclude that even in 15 day old cultures, undifferentiated embryonic stem cells can persist that are capable of forming tumors when transplanted.

Scientists still do not know so much about how stem cell differentiation is controlled. Further research will explain how cell signals operate to trigger cell differentiation. Current stem cell treatments may eventually become routine and regular therapies for serious disease. However, it's important that the safety of these therapies is evaluated and that caution is displayed before a therapy becomes accepted for use. This will allow full benefits of stem cell therapies for everyone.

The enemy of my enemy is my friend - Can bacterial viruses be used as antibiotics?

Viruses, often guilty of causing diseases in animals and plants, usually have the reputation of being the bad guys. But that is not true for all the viruses, it seems: some of them can actually be friends. A group of viruses which are capable of destroying bacteria, can be used for battling bacterial infections. These are termed bacteriophages, literally meaning “to-eat-bacteria”.

An article in the journal Biomacromolecules, April 2013, reports that, bacteriophages attached onto clinical surfaces, can be used to successfully eliminate biofilm formation by pathogenic bacteria, thus offering an effective means of controlling hospital-related infections. The researchers covalently attached two bacteriophages, coliphage T1 and staphylococcal bacteriophage Φ11, to polyethylene (PE) and polytetrafluoroethylene (PTFE) surfaces, and evaluated their effectiveness of combating two bacterial pathogens, E. coli and Staphylococcus aureus. The results revealed that the attached phages successfully retained their biological activity of infecting and destructing bacteria. Furthermore, it suggested that the two phages, attached simultaneously, have the ability of controlling multibacterial colonies.

[Image: usingbacteri.gif]

The idea of using bacteriophages as antimicrobial agents goes back a long way. According to literature, phages were used as therapeutic agents for treating bacterial infections since 1920s, following their discovery in 1917. Soon after the introduction of antibiotics in the 1940s, phage therapy was abandoned. However, antibiotics, once thought to be the brilliant solution against bacterial infections, have now proved otherwise. Despite the wide array of antimicrobial compounds introduced over the years, bacteria are increasingly becoming resistant to the antibiotics. Owing to the multidrug resistance of most pathogenic bacteria, the focus is back on bacteriophages as antibacterial agents. It is hoped that phage therapy could be used for successfully treating and preventing diseases caused by antibiotic resistant bacteria.

Bacteriophages are believed to possess many advantages over chemical antibiotics.

1. During an attack, phages, unlike antibiotics, can proliferate where it is needed, thus instinctively increasing the dose of the agent, while the antibiotic molecules are metabolically destroyed during the treatment. Therefore in contrast to the chemical antibiotics, a single dose or less frequent doses of phages can be effective in treatment.

2. Phages, being capable of undergoing genetic alterations, can overcome bacterial mutations. But antibiotics are chemicals that cannot adapt to a bacterial mutation and therefore become ineffective as the bacteria develop resistance traits.

3. Bacteriophages selectively target the pathogenic species of bacteria, while many broad spectrum antibiotics destroy the normal flora that can be beneficial in preventing the invasion by pathogens.

4. Phages have demonstrated an ability to clear bacterial biofilms which are resistant to chemical antibiotics. This may be attributed to the potential ability of the phages to actively penetrate into biofilms by lysing the bacterial layer, or due to the secretion of depolymerases that degrade the biofilm exopolymer.

There are also some limitations to page therapy.

1. Bacteriophages have a relatively narrow host range. Although this trait is advantageous in a sense, it can also be a handicap in treating multibacterial infections.

2. Bacteriophages, being foreign proteins, tend to be rapidly cleared from the circulation of humans. And there is a potential of the human immune system, mistakenly identifying the page-therapeutic agent as a pathogen, producing anti-phage antibodies to neutralise the page. There is also some risk of triggering allergic reactions to the phage particles.

Researches are being carried out on the prospect of genetically engineering bacteriophages in order to overcome these drawbacks and enhance the biological activity and effectiveness of phage antimicrobials.

Currently, many companies are involved in the development of phage-bases products for various sectors. Such products are being used as additives to control contaminations in food and animal feed, for treating plant diseases, in rapid detection test kits etc. Although phage therapy has yielded successful results in animal models, their application in treating humans is still limited. There is hope that bacteriophages, used in combination with antibiotics, is a potentially successful strategy to battle the ever developing antibiotic resistance of bacteria.[/align]

Further Reading:
1. Carlton, R. M. (1999). Phage therapy: past history and future prospects. Archivum Immunologiae et Therapiae Experimentalis-English Edition, 47, 267-274.

2. Hermoso, J. A., García, J. L., & García, P. (2007). Taking aim on bacterial pathogens: from phage therapy to enzybiotics. Current opinion in microbiology, 10(5), 461-472.

3. Loc-Carrillo, C., & Abedon, S. T. (2011). Pros and cons of phage therapy. Bacteriophage, 1(2), 111-114.

4. Pearson, H. A., Sahukhal, G. S., Elasri, M. O., & Urban, M. W. (2013). Phage-Bacterium War on Polymeric Surfaces: Can Surface-Anchored Bacteriophages Eliminate Microbial Infections?. Biomacromolecules.

Researchers at the Knight Cancer Institute at Oregon Health & Science University have made a new discovery giving hope to patients suffering from two types of leukemia previously thought untreatable. They have hypothesized about a new and efficient way to diagnose these types of leukemia. The discovery also leads to believe that existing treatment for different types of cancer may be used to treat this two forms of leukemia.

The study isolated the molecular mutation that causes chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) in some patients. That specific mutation, found to occur in a gene called colony stimulating factor 3 receptor (CSF3R), begins a chain reaction involving other cancer-related gene families known as SRC, JAK, and TNK2, which in turn activates and drives these diseases.

This discovery is useful in that it will greatly aid physicians by providing an effective diagnosing method for these types of leukemia, which currently present difficulties for physicians to distinguish from other types of leukemia. Moreover, the study results suggest that these patients, previously thought to be beyond help, could be helped by existing FDA-approved drugs, targeting other types of cancer, which were designed to inhibit the chain reactions impacting JAK and SRC/TNK2. Clinical trials are needed to prove this concept, though.

"Our ability to rapidly pinpoint a new cancer-driving mutation demonstrates the power of integrating improved genome sequencing technology. It will accelerate our ability to tailor treatments to individuals and each research victory gives us more insight into the nature of this complex disease. What distinguished this research was our method for matching voluminous amounts of gene sequencing data with drug sensitivity data to quickly deduce which mutations were relevant in causing disease. This allows us to make a difference for patients who don't currently have good therapeutic options." - said Jeffrey W. Tyner, Ph.D., an assistant professor with the OHSU Knight Cancer Institute and Cell & Developmental Biology Department, chef of the study leading laboratory.

Tyner and the other researchers on this study used a combination of tests that are not yet commonly deployed for testing primary cancer specimen, and noted it showed success. They first performed gene sequencing on specimens from 27 patients, creating an experimental profile of the possible genetic causes of these diseases. This subsequently enabled them to highlight the important mutations that were found to be common among CNL and aCML patients. Simultaneously to gathering information about the possible genetic markers, they performed tests on fresh cell samples from these patients, testing the effects of different drugs. This enabled the teams to link, with substantial statistical significance, drug efficacy to CSF3R gene mutations.

This approach from two sides simultaneously allowed the researchers to identify a primary cause of these rare forms of leukemia. Of the 27 patients in the study, 16, or about 59 percent, had the CSF3R mutation.
"This approach allows us to rapidly discover mutations that are fundamental to cancer growth and identify drugs that might be used to combat them. Our findings are not only promising for the treatment of patients with CNL and aCML but also validate our approach to identify new drug targets in cancer." said Julia Maxson, Ph.D., of the OHSU Knight Cancer Institute, who was first author on the study.

During the study period, a CNL patient was given the FDA-approved drug ruxolitinib, which is designed to inhibit the cancer cell growth initiated by the CSF3R mutation. This novel treatment resulted in a dramatic improvement in the patient's condition.

CNL and aCML impact up to several hundred patients in the United States each year. Patients suffering from these conditions typically live only two to three years post diagnose. These forms of cancer have also been difficult to even diagnose because there wasn't enough known about their primary genetic drivers. Knowing that they are defined by mutations in CSF3R provides physicians with a means to confirm a diagnosis. Tests for this mutation have already been available, yet no one knew that they can be used to diagnose this specific conditions; the OHSU Knight Diagnostic Laboratories' GeneTrails panel for leukemia has the capability to check for this mutation.

Jerald Radich, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, wrote that the approach is "an example of what genetically informed treatment may look like in the near future. This is how we will beat cancer, one gene, one disease at a time."

The study was published in the May 9 edition of the New England Journal of Medicine

The title of this article might have been dilemmic, but it's true! Death of muscle cells infuses life in muscles! In a recent research publication of Amelia E. Hochreiter-Hufford et al., in The Nature, published on 24 April 2013, role of Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion was described. Let me brief the jest of this research, first by throwing some light on the terms used above:

Myoblast Fusion:

The birth of skeletal muscles takes place when precursor-myoblast cells fuse together to form multinucleated myofibres. So, the term myoblast fusion indicates the birth of muscles.

Following is a very short view of how human myoblasts fuse together:

Apoptotic cells

Most of you must be familiar with the term," Apoptosis". Apoptosis refers to programmed cell death. And, so apoptotic cells are those at the verge of death (death programmed in the genome).

Phosphatidylserine receptor BAI1
BAI1 is a membrane protein (a GPCR in nature, the 7 -pass protein family) of the phagocytes which is well known for mediating the recognition of phosphatidylserine (chemically 1,2-diacyl-sn-glycero-3-phospho-L-serine, a phospholipid) on apoptotic cells.
So, till date, it was only known that during phagocytosis, the BAI1 GPCR recognized the universal marker of phosphatidylserine on apoptotic muscle cells, completing the cell death, untill recently, when Amelia E. Hochreiter-Hufford and team from University of Virginia, established the fact that "without apoptotic cells, new cells can't be born!"

Simple Experiments Which Proved The Same:

Growth Experiment:

C2C12 myoblasts (a mouse myoblast cell line), exhibit no growth/fusion in fully supplemented growth medium. But when apoptotic myoblasts are added to this culture, the fusion starts taking place to give birth to new muscle cells!!

zVAD Experiment:

zVAD is a caspase inhibitor, which inhibits apoptosis. Whereas fusion was inhibited in zVAD treated cultures. Collection of floating cells (apoptotic cells) from non-zVAD treated cultures to the zVAD treated culture activated myoblast fusion/birth of muscles!

Phosphatidylserine Masking:

As, mentioned earlier, phosphatidylserine is the universal marker of apoptotic cells. When, it's masked using GST-TSR protein, myoblast fusion cannot take place. Again establishing the significance of recognition of the presence of apoptotic cells in the vicinity of growing myoblast culture.

BAI1 Overexpression:

Increase in the expression of BAI1 protein increased the rate of fusion, again establishing the close link between the apoptotic cells and new cells.

Casp3−/− Mice Test:

It was observed that Casp3−/− mice (those lacking caspase 3: an apoptosis protein) have stunted growth when compared to the control set of mice. Their skeletal muscle growth was much lesser than the control set.

Briefing the Concept:

When myoblast fusion is about to take place, a fraction of the cells follow the apoptotic path of expressing phosphatidylserine on their surface, which is recognized by the BAI1 protein on the phagocytes. The triggering of expression of BAI1 protein in turn catalyzes the myoblast fusion process by activating ELMO/Dock180/Rac1 pathway (an indispensable pathway for cytoskeleton arrangement and fusion of myoblasts). Mingjian Lu & Kodi S. Ravichandran's publication on "Dock180–ELMO Cooperation in Rac Activation" gives a brilliant detail of this pathway. Blocking the apoptosis tends to impair the fusion, while catalyzing the same tends to do the favor to fusion. In Human myoblasts also, it has been found that myotubes synthesis is triggered upon addition of apoptotic cells. It must be kept in mind that it's not the apoptotic cells which take part in fusion. Once a fraction of cells is differentiated towards apoptosis, it will progress to death ultimately, but it tends to trigger the fusion among the healthy myoblasts through contact-mediated signalling with the neighboring cells. Even an injured muscle tissue won't get repaired if the apoptotic pathway of the cells is blocked/inhibited. The same was observed in cas-/- and bai1-/- mice, which exhibited no repair of injured tissue as compared to the control set of mice. Thus establishing the fact that "Without Apoptosis of Muscle Cells, One Cannot Imagine The Birth of New Muscles!"

Conclusion:

These findings set a capstone in the field of muscle growth/regeneration/degeneration studies. The recognized role of apoptotic cells in muscular development can change the approach towards treatment of myo-degenerative diseases like muscular dystrophy/paralysis etc. Also, ex-situ culturing of muscle cells will be very easy now having realized the catalyzing power of overexpressed BAI1 protein/phosphatidylserine. Considered altogether, the research is exceptional and highly productive in terms of it's utility for the field of medicine.

References/Suggested Readings:

Amelia E. Hochreiter-Hufford, Chang Sup Lee, Jason M. Kinchen, Jennifer D. Sokolowski, Sanja Arandjelovic, Jarrod A. Call, Alexander L. Klibanov, Zhen Yan, James W. Mandell & Kodi S. Ravichandran. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion: Nature 497, 263–267 (09 May 2013)

Park, D. et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430–434 (2007)

Mingjian Lu, Kodi S Ravichandran. Dock180-ELMO cooperation in Rac activation:Methods in Enzymology:406:388-402 (2006)

Have you ever observed a drop of coffee/any colloidal solution drying? If you've observed it carefully, you'll find that it dries up in a ring form-the particles collect together at the boundary of the drop while the liquid evaporates. This is termed as coffee ring effect. Following is a typical coffee dried drop stain!

Image Source: http://mrsec.uchicago.edu/research/highl...ing-effect

What Causes Coffee Ring Effect?

For coffee ring effect to take place, the liquid must be having high surface tension (as is the case with most colloidal solutions). Due to high surface tension, the liquid droplet doesn't shrink at circumference, but rather pins to the surface and a capillary movement of the solute takes place towards the boundary of the liquid drop. This phenomena leads to accumulation of all the liquid solute at the periphery.

Following is an attempt to show you the movement involved:

Significance of this effect:

Scientists have been trying to counter the effect for long owing to it's industrial implications like the need of uniform spreading paints/dyes/varnishes which shouldn't exhibit coffee ring effect. Though in some instances, it has been tried to use it to advantage too-like developing very fine wires out of colloidal gold, and it's role in stretching the DNA in solution.

Bacterial broths don't exhibit Coffee Ring Effect!:

Surprisingly, most of the bacterial broths/culture don't exhibit coffee ring effect despite being fairly dense colloidal solutions. Recently, the work of Wouter Sempels et al.,(2013) established the auto-production of biosurfactants as the reason behind the ability of the bacterial systems to counter the coffee ring effect. Their model bacteria was Pseudomonas aeruginosa which is highly pathogenic in nature, and is known to cause infections in open wounds. It's ability to avoid the coffee ring effect enables it to infect on as large breeding ground as available on/in the wound, rather than just concentrating on the periphery of the wound. And, the research group of Wouter Sempels found that it was the production of biosurfactants by this bacterium, which attributed such infecting traits to it. The surfactant produced by it was Rhamnolipid

Culturing of mutant strain of P.aeruginosa lacking the gene responsible for rhamnolipid synthesis, lead to coffee ring like bacterial spots on agar plate, confirming the role of the biosurfactant in ensuring the homogeneous growth/spread.

Significance of Countering Coffee Ring Effect to Bacteria:

Production of biosurfactants tends to provide the ability to swarm (spread on the surface) to the bacteria. The swarming increases as the population density of the bacteria increases (owing to greater production of the surfactant). This in turn enables the competing population to utilize the nutrients evenly, uniformily and maximally under the developing unfavorable condition(s). A clustered colony would tend to use the nutrients unevenly, with limitation of nutrient transfer to the core of the cluster and hence early death of the bacteria. It is thus a sort of response of bacteria to the unfavorable conditions, and the intimate need to counter the undesirable coffee ring effect situation.

Application of surfactant action in non-biological world:

Taking inspiration from the role of biosurfactant in ensuring homogenous spread of bacterial culture, if synthetic surfactants like detergents are tried on the normal coffee stain, it doesn't tend to reverse the coffee ring effect! Though it's surprising, but the explanation was given by Wouter Sempels et al., by asserting that surfactants can reverse the effect only in the colloidal solutions of very fine material/particles, as is the case of bacterial systems. The reversing of the coffee ring effect on fine particles by surfactants occurs by Marangoni flow (localized vortices & reverse capillarity). So, if one wants to reverse/avoid the coffee ring effect, use the particles of very fine size in the solution!

Industrial Implication of this research:

Clearly, the research has direct implications on the paint/varnishes/dyes industry. Where use of very fine particles with surfactants can make sure that the paint quality is superior in terms of the spreading properties. Further, addition of surfactants to nano-materials can also ensure the perfect distribution in the target site. The finding is indeed new and it's biotechnical/medical applications haven't been thought yet, but considering the easy availability of surfactants in the market, their overall industrial usability is expected to boom after this research. Apart from that, use of biosurfactants (which might be more compatible to biological systems) may get triggered in nano-technological research aimed at nano-particle delivery/distribution.

Suggested reads:

Wouter Sempels, Raf De Dier, Hideaki Mizuno, Johan Hofkens & Jan Vermant. Auto-production of biosurfactants reverses the coffee ring effect in a bacterial system. The Nature (April 2013)

Deegan, R. D. et al. Contact line deposits in an evaporating drop. Phys. Rev. E 62, 756–765 (2000)

Hu, H. & Larson, R. G. Marangoni effect reverses coffee-ring depositions. J. Phys. Chem. B 110, 7090–7094 (2006)

Definition:

On the basis of the health and environmental risk associated with biological agent, the biosafety levels are classified. Today various labs, research centers and institutes working with these agents are assigned with a corresponding containment level. In pharmaceutical industries and research Centre levels of biosafety are considered because of the need to experiment with live bacteria and viruses, in such industries, vaccines and other biological products are developed. Example is influenza virus which is considered at higher safety level. Knowledge of such bio safety level makes people aware of the associated risk.

Biosafety Level 1 (BL1)
BL1 includes biological agents that present a low risk to personnel and the area; environment. Examples of BL1 agents are Agrobacterium radiobacter, Bacillus thuringiensis, , Aspergillus niger, Escherichia coli strain K12, Micrococcus leuteus, , Lactobacillus acidophilus, Neurospora crassa, Serratia marcescens , and Pseudomonas fluorescens.
Basic precautions are required in case of A BL1 containment laboratory. Work may be done in fume hood, on open bench tops. When working in such laboratory, standard microbiological safety practices are used. Washing hands with anti-bacterial soap and disinfecting all exposed surfaces in the lab while using cell and bacterial cultures. Autoclave of material used for cultures can be safe practices. Gloves and face masks may also be recommended.

Every BL1 lab staff need to be trained on the procedures and be supervised by a senior or scientists with general training in microbiology and safe practices.

Biosafety Level 2 (BL2)
A BL2 biological agent presents a moderate risk to personnel and also to the environment. Best examples of biosafety level 2 are Mycobacterium, Salmonella choleraeusis and Streptococcus pneumonia. These organism exist a moderate risk to personnel handling them and to the environment. In case the accident happens and the person is exposed to this laboratory BL2 microorganism, there is little risk of it spreading and also the risk of infection is low.

Access to a BL2 laboratory is restricted so that the safety level of personnel is maintained even though the person is not aware of it. There are autoclaves in such laboratories to decontaminate biological waste material and also the use of biological safety cabinet is important to avoid exposure of BL2 microorganisms. The use of personal protective equipment that is Coats, gloves and face masks is mandatory in such laboratories. Trained persons and scientist supervise such laboratory work in order to maintain the safety of people and environment.

Biosafety Level 3 (BL3)
BL3 biological agents are organism which can cause serious diseases in humans, animals and also in plated whenever they are exposed. Examples of microorganism in this classification are Leishmania donovani, Mycobacterium tuberculosis, Francisella tularensis, Bacillus anthracis, West Nile Virus , Chlamydia psittaci, Venezuelan equine encephalitis virus,SARS coronavirus, , Eastern equine encephalitis virus, Salmonella typhi, Rift Valley fever virus, Coxiella burnetii and Rickettsia rickettsii.
BL3 agents also include those that could cause serious financial loss in terms of their spread in the environment and going forward in various continents. BL3 containment labs must strictly adhere to safety practices and employ safety equipment and facilities that are appropriate when working with such biological and other BL3 agents. Not only the precautions are important but also the treatments are essential in case of exposure to these agents. Research working with the deadly viruses and other like H5N1 virus, for example, must be performed in a BL3 containment lab. All the staff must be trained on safe practices of laboratories, handling of microorganism and other biological generations. The handling of potential pathogens is critical and training in this case can give an extra knowledge and awareness of it. The biological safety cabinets are essential in such labs and the risk to personnel is thus minimized during the period in which they handle these agents.

Biosafety Level 4 (BL4)
BL4 biological agents can cause serious or lethal diseases in humans, animals and plants that are untreatable. Examples of biosafety level 4 are Marburg virus, Bolivian and Argentine hemorrhagic fevers, Ebola virus, Crimean-Congo hemorrhagic fever, Lassa virus, smallpox, and other viruses which causes hemorrhagic diseases. Infection with these agents can produce lethal disease which can even cause death if not treated immediately. Another danger of these agents is that they can be easily transmitted from one individual to another. Also there is a chance of cross contamination that is from animals to humans and also vice-versa. The transmission can take place with contact or even through air which is lethal.

Such facilities are controlled and isolated form other working area to avoid contamination. Such facilities are often maintained in negative pressure to avoid contamination through an aerosol.

Migraine is neurological chronic disorder. Characteristic of this disorder is recurrent headache which can be very severe. Sometimes, these headaches could be followed with some autonomic nervous system symptoms. Other symptoms like nausea, vomiting, photophobia and phonophobia can occur as well.

Migraines are considered as both environmental and genetic disorders. Because two- thirds migraine patients have positive family anamnesis, scientists focused on genetic research in order to discover which genetic links are responsible for migraine incidence. Also, two- thirds of patients are women, and it shows that female hormones like estrogen have significant role in migraine development.

However, many migraine suffering people can be optimistic, because scientists on Brigham Young University revealed their newest discoveries, and results are in every way promising to scientists.

Professor at Brigham Young University (BYU), Emily Bates suffered severe migraine attacks when she was young, and she decided to dedicate all her knowledge to research migraine cause. According to latest findings she has done great job, and now she is one step closer to complete understanding of migraine disorder.

Considerations of migraine genetic basis

Professor Bates and other two lead researchers discovered two gene families with very similar genetic mutations. They tested these genetic mutations on mice, and results were encouraging. They hope that these results will stimulate research for effective medicines for migraine attacks. While single mutation is not that common (scientific project that included 27,000 people), position of mutation and normality of the symptoms suggest this study can influence on many patients with migraine disorder.

Role of the transformed gene

It is discovered that mutation occurs when an enzyme, casein kinase delta (CKlδ), becomes an impared enzyme. Mutated gene has many functions in cell. One of the most important gene roles is removal of waste and neural transmitters. In comparison with other genes, discovered from various studies, this gene can hit on common causes of migraine. Other genes are connected with severe or rare forms of migraine disorder.

Directions for future researches

Scientists can see several malformations in brain cell cultures with mutated genes. First of all, neurons are completely normal. However, problem occurs in astrocytes cells. These cells show unusual behavior. Astrocytes are specialized neural cells, and they present bigger cell family then neurons. In neural tissue, astrocytes have function to remove extra neural transmitters and other waste. Mutated astrocytes have another behavior, and they can make brain blood vessels hyperactive and hyper- responsive to brain activity. This phenomenon can cause migraine pain.

Role of the estrogens in migraine pain

Steroid hormones mediate their activity via their receptors, which are widely distributed in human organism. Estrogen receptors are founded in some brain regions which are considered as potentially involved in migraine disorder pathogenesis. Lower level of estrogen in human body is important migraine trigger. When woman has low level of estrogen after exposure to high levels of the hormone for several days, estrogen- associated migraine can occur.

The mutated gene is also responsible in estrogen induced migraine pain. This gene codes a protein that interacts with estrogen receptors. According to this, women are more vulnerable for this disorder development. This theory can very likely explain why women are two- thirds of all migraine patients.

Particular gene mutations associated with sleeping disorder

Analyzing individual genes with plenty of common genes is not that simple. Often, scientists find it difficult, because they cannot focus on target genes. However, they found out that rare sleeping disorder is related to migraine. After that discovery, they included two families with migraine pain associated with rare sleeping disorder in study. This sleeping disorder is very unusual. Patients with this syndrome fall asleep at 7 p.m. and wake up 4 a.m.

Importance of this discovery is that scientists have never been so confident that one gene is related to migraine disorder. When they are so confident about this discovery, it is just a matter of time when they will find medications for migraine disorder.

Researches on mice

When scientist found out which gene is related to migraine disorder, they began experiments on mice. The goal of this experiment was evidence that mutation of certain gene causes migraine- symptoms in another mammals.

Results were measured in two ways. One researcher tried to compare mice brain activity with human brain results like auras, fuzzy lights and vision loss. On the other side, another team of researchers, led by professor Bates, tried to measure characteristic pain and sensitivity in mice. They used nitroglycerine for mice migraine test, substance which is used for chest pain in human, and induces migraine in human population. Both ways have shown that mutated genes can induce migraine in mice, further solidifying the connection between migraines in humans and mutated gene.

Conclusion

Migraines are not so good researched topic in medicine. Traditionally, these disorders are difficult to treat, not just because of their complexity, but because scientists and doctors know so little about them. Every single drug used in treatment of migraine is created for another health disorder. However, these drugs are used with certain dose of efficiency in treatment of the symptoms, but for patients, much more is needed. Discovery of mutation, when casein kinase delta (CKlδ) becomes impaired, offers promising solutions for new ways of migraine treatment and drug development. Unfortunately, it will take many years from now to bring such drugs to market, but these medications could possibly help more than 12 percent of people on the globe. This experiment and its results are just a first step on a long way of revolutionary discovery, and if scientist want to improve their knowledge about migraine, they will have to look in finer parts of genetic pathway.

Botulinum neurotoxin, produced by the anaerobic bacterium Clostridium botulinum is the most potent biological toxin identified thus far. A minute amount of botulinum toxin can lead to botulism, resulting in paralysis of muscles, even in death.

Seven different serotypes of botulinum neurotoxin, designated A to G, are produced by different strains of C. botulinum bacteria. Those serotypes are antigenically diverse but similar in structure, molecular weight and mode of action.

The neurotoxin blocks the release of acetylcholine, the principal neurotransmitter at the neuromuscular junctions where a muscle fibre meets a motor neuron. This interferes with the transmission of nerve impulses from the central nervous system to the muscle, hindering the muscle responding to motor neuron activity. This paralyses the muscle, making it weak and unusable.

Therapeutic Use of the Deadly Toxin

Despite its deadliness, physicians worldwide consider botulinum toxin as the most effective treatment for numerous movement disorders related with increased muscle contraction. Only the type-A botulinum toxin is currently available for clinical use. Three different preparations of botulinum toxin A exist in the market, namely, OnabotulinumtoxinA (marketed as Botox® & Botox® Cosmetic), AbobotulinumtoxinA (marketed as Dysport®) and RimabotulinumtoxinB (marketed as Myobloc®).

The drug is injected in minute doses into affected muscles or glands where it induces localized muscle paralysis by inhibiting transmission of neurons. This mechanism enables the toxin to relieve neuromuscular disorders that cause spontaneous contractions of muscles. Subsequent injections given at regular intervals will usually be required following the initial dose.

FDA Approval for the Use of Botulinum Toxin type A

Botulinum toxin type A was first approved by the FDA in 1989. In a news release issued in 2009, FDA announced that

Quote: Botox®, Myobloc®, and Dysport® are approved by the FDA for the treatment of a condition marked by repetitive contraction of the neck muscles (cervical dystonia). Botox® Cosmetic and Dysport® are approved by the FDA for dermatologic use in the temporary improvement in the appearance of frown lines between the eyebrows called glabellar lines. In addition, Botox® is approved for the treatment of severe underarm sweating (primary axillary hyperhidrosis), crossed eyes (strabismus), and abnormal tics and twitches of the eyelids (blepharospasm).

In 2010 FDA accepted Botox® injection for preventing chronic migraine in adult patients and recently in 2013, FDA expanded the use of Botox® to treat overactive bladder in adults.

FDA requires all of the botulinum toxin products to display a boxed warning and a medication guide. FDA also notes that these different products are not interchangeable due to difference in the units used to measure the products.

Other Possible Uses of Botulinum Toxin type A

Pioneered in 1981 by Dr. Alan Scott, an ophthalmologist, a significant amount of researches has been done over the years on the medicinal use of botulinum toxin. A recent study published in the medical journal Neurology in July 2012, reported that the botulinum toxin type A can help prevent shaking in the arms and hands of people with multiple sclerosis.

Moreover, various studies suggest the use of the toxin to treat disorders such as spasticity and other forms of muscle overactivity, hemifacial spasm (automatic facial contractions), some voice disorders (adductor laryngeal dystonia), focal limb dystonias (such as writer’s cramp)etc. There is also evidence of botulinum toxin effectively in reducing lower back pain.

However, FDA has not yet approved the use of botulinum toxin products as a treatment of muscle spasticity.

Possible Side Effects

Patients may experience short-term and mild side effects such as general weakness of the injected muscle following treatment, pain at the injection site, symptoms imitating influenza, headache and stomach disorders. FDA reports that during clinical trials regarding urinary incontinence, urinary tract infections, painful urination, and urinary retention have also been observed. When used as a cosmetic, symptoms have been reported such as drooping eyelid or the incapability of closing the eyes lids, double vision, uneven smile etc.

A paper published in the Journal of American Academy of Dermatology in 2005 informs that 28 deaths due to use of Botox® as a therapeutic agent have been reported to FDA between 1989 and 2003 though no deaths were reported from the cosmetic use of Botox®.

FDA now requires the labels of the commercial toxin preparations to indicate that there is a risk of the diffusion of toxin into adjacent tissues following injection, thereby causing botulism-like symptoms. Those symptoms could include swallowing and breathing difficulties that can be life-threatening. However, FDA also notes that adverse effects of spread of toxin have not been reported when Botox® is used at recommended doses.
Contradictory Research

A research published in the Journal of Biomechanics in 2011 raises questions about the therapeutic use of botulinum toxin A. It reports that clostridium toxin type A (Botox®) can produce weakness in target and non-target muscles. The study also reveals that repeated injection of the toxin induced degeneration of muscles. This is the first report to reveal such adverse effects caused by the toxin during clinical use.

Another study suggests that botulinum toxin may not be useful for treating migraine. However, more research is required in order to come to a conclusion.

In Conclusion..

Due to its effectiveness and relative safety botulinum toxin A still holds grounds as an invaluable treatment for neuromuscular disorders. Yet, more insight is required on prolonged clinical use of the toxin, especially with children and adolescents.

References:
1. Coté, T. R., Mohan, A. K., Polder, J. A., Walton, M. K., & Braun, M. M. (2005). Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. Journal of the American Academy of Dermatology, 53(3), 407.

2. Fortuna, R., Aurélio Vaz, M., Rehan Youssef, A., Longino, D., & Herzog, W. (2011). Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox). Journal of biomechanics, 44(1), 39-44.

3. Münchau, A., & Bhatia, K. P. (2000). Regular review: Uses of botulinum toxin injection in medicine today. BMJ: British Medical Journal, 320(7228), 161.

4. Naumann, M., So, Y., Argoff, C. E., Childers, M. K., Dykstra, D. D., Gronseth, G. S., ... & Simpson, D. M. (2008). Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review) Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 70(19), 1707-1714.

5. Prescott, L.M., Harley,J.P., and Klein, D.A. (2008) Microbiology-5th ed: pp 930, McGraw-Hill Higher Education.

6. http://www.fda.gov/newsevents/newsroom/p...149574.htm

7. http://www.fda.gov/Drugs/DrugSafety/Post...143819.htm

8. http://www.fda.gov/NewsEvents/Newsroom/P...269509.htm

9. http://www.fda.gov/NewsEvents/Newsroom/P...269509.htm

The Department of Bioinformatics was started in the academic year 2004 to enable ing students understand and learn the fundamental principles of Science through optimal methods of teaching.
The Department has well experienced, highly qualified and dedicated faculty members who encourage students to achieve their career goals. The department has independent laboratories for conducting biotechnology and bioinformatics experiments. The Department has been conducting workshops and guest lectures on a regular basis so as to update the knowledge of students. Industrial visits for students to gain insights about the industrial needs are also undertaken. Seminars by students provide an opportunity for improving their communication skills.
The Department imparts professional training in core Biotechnology and Bioinformatics areas. It offers a 3 year UG B.Sc Biotechnology and Bioinformatics (Dual Degree) and 2 year PG degree in Bioinformatics. Emphasis is on subjects such as Microbiology, Immunology, Molecular genetics, Bio - physics, Biochemistry, Genetic engineering, Structural Bioinformatics, Drug Design, C, C++, Database Management System and Bio - statistics.
At the post graduate level various life science subjects including Plant Biotechnology, Animal Biotechnology, Enzyme Technology, Industrial Biotechnology, Genomics & Proteomics, and Systems Biology are covered as a part of their syllabus. The syllabus is designed keeping in mind the rapid and constant progress in life science areas. To enhance the skills of students, the course also has a compulsory one month of summer training and three months of project. Further, multi - disciplinary learning approach encourages team - working and effective expression of ideas.
Life Sciences industry has always witnessed demand for talent. Students have excellent opportunities in several areas both in India and overseas that includes Research & Development, Drug Design, Pharmaceutical companies, Clinical Trials and Bio IT companies.

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Amazed by the title?? Well, you must be! But, this is true indeed as per the recent research carried out by a group of scientists from the University of Oxford (UK), University College London (UK) and Innsbruck Medical University (Austria), published in the 'Current Biology' on 16 May 2013! (Yes!, this is that recent!). The research has highlighted the utility of non-invasive noise stimulation of brain to enhance the high level cognitive functioning of the brain as well as the specific functioning of the brain (viz. solving complex arithematics!).

[Image: What-can-binaural-beats-be-used-for.jpg]

Image free to use

Cognitive functioning of the brain deals with processing of thoughts, memory and speech. And, until this very research, non-invasive brain stimulations were known to enhance the basic cognitive/behavioral responses only. This group utilized a specific mode of stimulating the brain at a specific region for improving the mathematical learning of the targets. Transcranial Random Noise Stimulation (TRNS) was the mode targeted at bilateral Dorso Lateral Prefrontal Cortex (DLPFC) region of the brain. The pre-frontal cortex is known for it's role in arithematic understanding and analysis.

TRNS sends random pulses of electric current to the pre-frontal cortex through the electrodes attached to the scalp. In order to monitor the effect of TRNS, pre-frontal hemodynamic (blood movement) responses in the brain are monitored by coupling TRNS to near-infrared spectroscopy (NIRS), which indexes the level of brain activity in terms of the Oxi-haemoglobin rich blood supply to the brain. Following is the original photograph of the set-up, obtained from the open-access paper available at Science-Direct

(Link to Paper):

Earlier in 2010, Cohen Kadosh, the member of this team from University of Oxford had come up with Transcranial Direct-Current Stimulation (TDCS) as a way to enhance memory and learning power of the volunteers involved in his research. His method aimed at neural activation in particular regions of the brain with parallel silencing of others, by continously passing current between electrodes installed at different parts of the scalp. The speculations on the safety of this approach of continuously passing current to the brain were obvious and expected! Cohen thus worked on making the approach more specific and effective, and the team came-up with TRNS.

In this research, 25 volunteers from University of Oxford were chosen and divided in two groups: TRNS and Control. The TRNS group received over 20 min of "electric shock!" (don't take it otherwise, it was random pulses of DC, not sheer shocks!), while the control received 5 seconds shock period. Both the groups were given training on solving a particular type of complicated arithematic problem(s), which continued for 5 days. TRNS group turned out to be a very fast learner as compared to the control group (called 'Sham' in paper).

In order to check the long-term neuroplastic effects, the volunteers were surprise called after 6 months and asked to solve the similar mathematical problem(s). The TRNS group again turned out to be the faster and accurate one, when compared to Sham. The findings were supported by the NIRS data, which exhibited high activity of pre-frontal cortical region of brain in TRNS group both during the active study and after 6 months!

Apart from the deep-level training to both the groups on a particular arithematic problem(s), a shallow training was also given on another kind of problem. TRNS group though performed well during the active period of the study, it couldn't perform well after 6months on the shallow trained task. This highlights the fact that, TRNS alone doesn't makes the cognitive functioning "high-level/extra-ordinary", but it needs to be coupled with good/deep training regime for long-term effects, which would be better than normal-individuals or non-TRNS people. Apart from this, the small size of the target population (only 25 volunteers), makes the certainty of consistent out-come quite speculative yet-again. Validation of the findings through the test on bigger target groups would be more reliable.

Nevertheless, the unique research highlights the possibility of an altogether different way of enhancing cognitive-functioning among the people. Apart from helping the people with neuro-degenerative diseases, it can help the maths-scared pupils to enhance their grasp over the subject! Cohen aims at extending his research to a new set of students, who are not from the elite universities like Oxford, but from the rather less-pronounced institutes, which might waive off the possibility of default superior cognition. The findings till date are no-doubt promising, and let's hope, very soon we may find a machine to make us learn mathematics "very fast!"

References/Suggested Reads:

Albert Snowball, Ilias Tachtsidis, Tudor Popescu, Jacqueline Thompson, Margarete Delazer, Laura Zamarian, Tingting Zhu, Cohen Kadosh.Long-Term Enhancement of Brain Function and Cognition Using Cognitive Training and Brain Stimulation. Current Biology, 16 May 2013

Cohen Kadosh, R., Soskic, S., Iuculano, T., Kanai, R. & Walsh, V. Curr. Biol. 20, 2016–2020 (2010)

So much developments have taken place in the field of biotechnology that it might need an infinite array of books to compile them at a place altogether! So, I just thought about introducing you to "the" latest advances in this field. And, nothing could be as better as telling the tale of biotechnological success in the month just passed-April 2013. Rather, I've decided to update you all revered readers every month about the most recent developments in our field. A few of the selected topics will be detailed in subsequent articles, to shed some insight. Feel free to ask for the details on the topic of your choice among the enlisted developments, I'll make a full-fledged article on that too!

So here is the brief summary on the most recent developments as occurred/reported in April 2013:

1. New Treatments For Neuro-degenerative diseases

Lorenz Studer from Memorial Sloan-Kettering Cancer Center has developed a new way of replacing Parkinson’s affected neurons. It focuses on differentiating the embryonic stem cells to a specific stage of development (2-3 months in utero). They are injected into the brain just before they differentiate into cells with long/intricate branches. He has developed the mode to generate millions of identical young neurons for transplantation and has thus evoked the risk of stem-cell mediated tumours in the brain (a problem with earlier strategy, which used to inject embryonic stem cells directly). It will take 3-4 years for this research to enter clinical trials for humans.

2. 3D Printer to Create Internal Blood Vessels & Tissues!

Scientists from the elite University have done the feat beyond imagination! They have created a 3D printer which can handle stem cells and create human tissues/organs! Though the technology is just developed, the researchers hope that the printed tissues will be able to replace the damaged ones, once the finer details of translating the characteristics of natural tissues into the printed version are met!

3. Childhood Obesity Determinants Unveiled

A recent research published on 8 April 2013 in Pediatrics, has mentioned a specific "Obesogenic Environment" as a causative agent of childhood obesity. Eating more or Less Physical activity is not the causative agent but the interplay of minor environments of routine life like the "size of dishware" , "TV screen time", "sleep-periods", "level of attention" etc as the obesity determinants. According to the research group, a complete reboot of today's kids' environments needs to be done, which seems highly non-probable!

4. NASA's New Mission for Extra-Terrestrial Life

On April 5, 2013, NASA shared the details of TESS, Transiting Exoplanet Survey Satellite, for the future launch in 2017. It's the official successor of NASA’s Kepler mission aimed at searching the exo-planets and extra-terrestrial life. TESS's range will be over 400 times that of Kepler and is expected to find about 500-700 earth like/super earth planets.

5. The Healing Power of Placebos

Placebos, also known as Dummy Treatments have long been known to treat the diseases. Despite the fact that there's no medicinal component in Placebos, their efficacy in treating the diseases has always caught the attention of researchers across the globe. In a recent unpublished research by Ted Kaptchuk of Harvard Medical School (who has a long history of working on Placebo Effect) reported in the Scientific American (April 2013), MRI scans were used to compare the effects of delivering actual medicine and Placebos, which indicated an increase in activity of the prefrontal cortex and the anterior insula portions of the brain (related to pain/relief sensation). The medicine just had a direct and fast response in bringing the activity in brain, while placebo had a relatively slower one. The research which supplements the previous findings really establishes a strong case for potential use of Placebos for treatments.

Following is a fascinating documentary on "Placeo: Cracking the Code" from Harvard Placebo Study Group (2002):

6. A living fossil's Genome Decoded
Coelacanth-the living fossil found first by a fisherman in 1938, and known for revealing information about the tetrapods through which amphibians, birds and mammals came into being, has got into limelight again by the efforts of a huge team of scientists across the globe working together for the cause of decoding the genome of Coelacanth (Latimeria chalumnae). Their exhaustive phylogenetic analysis lead to a significant conclusion that it's the Lung Fish which is closest ancestor of tetrapods, not Coelacanth. The open access research paper can be accessed at Nature Magazine Link

7. Inauguration of 2 Big Studies on Brain
Obama announced the inauguration of 2 BIG "BRAIN PROJECTS" called THE BRAIN Initiative and the Human Brain Project with a generous funding of whooping $1.3 billion! Where as the BRAIN initiative aims at developing high-throughput technologies to enable scientists to take dynamic pictures of the brain that might show the way brain cells and complex neural circuits interact in the quick time frame of real time thoughts!; Human Brain Project aims at deep and all round studies of brain, mapping the brain to its entirety, decoding cures to degenerative diseases etc. It's first goal is to develop 6 ICT-based research platforms that can provide the technology to meet the objectives.

BRAIN initiative Fact Sheet

Human Brain Project Fact Sheet

8. Functional Transplant of Lab Grown Kidneys!

Massachusetts General Hospital in Boston showcased a once imagined research: growing a kidney in laboratory and transplanting it into a rat 'successfully!'. The work was published in The Nature Medicine (April 14). The research was headed by organ-regeneration specialist Harald Ott, wherein they used a 'donor kidney', and turned it into a scaffold of connective tissues & blood vessels, by removing the kidney cells and blood vessels and made a fully functional kidney out-of it using new-born rats' kidney cells and blood cells.

9. Use Light to Treat Pain!: Optopharmacology
Researchers from Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland have unveiled the finding of a light sensitive ligand "Optovin", that binds to the ion-channel for painful sensory stimuli detection. With this finding, scientists hope to control neural activity by using light and hopefully, they might soon find the optimal way of light-stimulus control, to manage the pain stimulus-leading to altogether new way of medicating the painful diseases/conditions, Optopharmacology!

10. Potential Block-Buster Heart Drug!
Hobbs & Cohen, the two pioneer scientists at University of Texas have for long worked on a gene named PCSK9, that encodes a protein having a significant role in controlling LDL Cholesterol. Their years old hypothesis on Mendelian form of inheritance of the mutant form of PCSK9 (which leads to rock-bottom cholesterol levels in the carriers of mutation), has today been converted into clinical trials of using the mutant form of PCSK9 as a potential drug for Cardiac disorders!! The entire research & background was published on April 11, 2013 in The Nature.

So, these were some of the most fascinating developments in the field of Biotechnology in the month of April 2013. The list doesn't covers all the developments, but those included in the list were intriguing indeed!

Thanks!

Spider silk can actually stop a train!

A group of physics students at United Kingdom's University of Leicester declare. According to their calculations, a single strand of silk from Darwin's bark spider (Caerostris darwini) proved to have the strength required to stop a moving train.

But that doesn’t surprise the scientist much. Assessed to be tougher than steel, even Kevlar (a synthetic material which is used to produce bullet proof vests), spider silk has long since attracted the attention of the scientists.

The combination of the unique strength, extensibility and tensile properties of spider silk makes it incomparable to any other substance, natural or man-made. Adding to those qualities, spider silk is naturally waterproof, biocompatible, and biodegradable. Most importantly, a recent study reported that bioengineered spider silks generate no toxicity or immunogenicity in humans, thus enabling it being used for biomedical applications.

Due to their exclusive properties, spider silk has received the attention of many industrialists. An amazing assortment of industrial products such as textiles, protective clothing, parachute cords, and airplane parts etc. can be produced with this material.
Spider silk also holds the promise for many biomedical applications including Band-Aids, wound sutures, drug carriers, artificial ligaments and tendons and organ implants. Another interesting use of spider silk will be in the cosmetic industry, enhancing the softness, toughness and brightness of products such as shampoo, soaps, nail varnish etc.

Can we harvest spider silk directly from spiders?

Unfortunately, we can’t. Since the spiders can’t be reared in farms due to their highly territorial and cannibalistic characteristics, researches are being conducted on transgenic production of spider silk. This involves genetically engineering other organisms to express the spider silk proteins, followed by the purification of the proteins and finally spinning those into silk strands.

But altering the genome of another organism to express the spider silk proteins is not as easy as it sounds, scientists declare. The complex nature of the genes encoding spider silk proteins poses the major obstruction in expressing natural-like transgenic spider silk in other organisms. Those genes contain large repetitive sequences with high GC contents making it hard to clone the respective genes using PCR.

Over the years, several efforts to produce recombinant spider silk proteins have been made with various hosts such as bacteria, yeast, mammalian cells, insects and transgenic plants. Each of these hosts expressed spider silk proteins but each endeavour presented their own complications.

Silk ‘Spinning’ Bacteria

The expression of the spider silk genes by bacterial hosts is not feasible due to the nature of these genes. It was found that bacteria, being prokaryotic, have difficulties decoding the gene codons of spiders. Furthermore, the gene expression in bacteria is size-limited. Therefore the bacteria, unable to express the lengthy repetitive gene sequences coding for the spider silk proteins, tend to remove those sequences by a mechanism of homologous recombination. This results in gene products with a lower molecular weight yielding silk fibres of inferior quality.

Since the codon usage of eukaryotic organisms is compatible with that of the spiders, and the gene expression in them is not size-limited, the scientists have made efforts using the eukaryotic cells as hosts in order to overcome this problem.

Silk ‘Milking’ Goats

One such experiment, carried out by the Nexia Biotechnologies, Canada, engineered the spider silk gene into the DNA of mammary epithelial cells of goats, thus producing transgenic goats that secreted the milk protein in their milk. This ‘milk silk’ was then purified and spun into and spun in to yarns of silk, dubbed ‘Biosteel’ by the company. However, these products did not adequately imitate the native spider silk fibres and the yields were not sufficient for industrial production.

Studies were also performed using other mammalian cells such as Baby Hamster Kidney cells, yeasts, plant cells and insect cells. Each of these effort yielded silk. But there were problems with the purification of the proteins and the yields were not sufficient for industrial applications. Furthermore, producing these organisms at large scale was difficult and uneconomical.

A Man Made Gene

A synthetic spider silk gene manufactured by the scientists has proved to overcome many of these hurdles. This artificial gene, having an adjusted codon usage can be used with any host including bacteria.

Bacteria Again

A study published in the journal Proceedings of the National Academy of Sciences in 2010 reports incorporation of the synthetic gene into E. coli which was then metabolically engineered by elevating its glycyl tRNA pools. This resulted in higher yields of recombinant silk protein with a molecular weight similar to that of authentic dragline silk protein of the spider Nephila clavipes. These proteins were then spun into silk fibres with mechanical properties comparable to those of the native silk.

Chimeric Silk Proteins

Another article published in the same journal in 2012 records the attempt to create transgenic silkworms using piggyBac vectors. These engineered silkworms could produce silk fibres composed of silk proteins containing both spider and silkworm characteristics. The article states that these fibres were tougher than the parental silkworm silk fibres and as tough as native dragline spider silk fibres. Since the silkworms were naturally capable of assembling the silk proteins into silk threads, this process has an added advantage.

However, a viable and economical technique of producing transgenic spider silk at industrial-scales is yet to be achieved.

References:

1. Dams-Kozlowska, H., Majer, A., Tomasiewicz, P., Lozinska, J., Kaplan, D. L. and Mackiewicz, A. (2013), Purification and cytotoxicity of tag-free bioengineered spider silk proteins . J. Biomed. Mater. Res., 101A: 456–464. doi: 10.1002/jbm.a.34353

2. Teulé, F., Miao, Y. G., Sohn, B. H., Kim, Y. S., Hull, J. J., Fraser, M. J., ... & Jarvis, D. L. (2012). Silkworms transformed with chimeric silkworm/spider silk genes spin composite silk fibers with improved mechanical properties. Proceedings of the National Academy of Sciences, 109(3), 923-928.

3. Vendrely, C., & Scheibel, T. (2007). Biotechnological Production of Spider‐Silk Proteins Enables New Applications. Macromolecular bioscience, 7(4), 401-409.

4. Xia, X. X., Qian, Z. G., Ki, C. S., Park, Y. H., Kaplan, D. L., & Lee, S. Y. (2010). Native-sized recombinant spider silk protein produced in metabolically engineered Escherichia coli results in a strong fiber. Proceedings of the National Academy of Sciences, 107(32), 14059-14063.

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