transcription dna to rna

August 23, 2014, 11:20 am

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During transcription of DNA to RNA, where does the ribose sugar of the RNA transcript come from? Does the RNA polymerase have all those sugars stored inside of it?

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Ebola Virus: Development of Vaccines and Therapeutic Drugs

August 28, 2014, 1:43 am

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The 2014 outbreak of Ebola virus highlights the urgent need to develop an effective vaccine to prevent the spread of this deadly virus, and effective therapies to improve survival rates among those infected with Ebola. A DNA vaccine candidate should begin clinical trials in humans this year, and investigational drugs in development to treat patients suffering from viral hemorrhagic fever include monoclonal antibodies, siRNA-based therapeutics, and antiviral small molecule drugs.

Ebola Vaccines (preventative drugs) currently in development:

Researchers are developing a vaccine for Ebola that contains an attenuated live virus, vesicular stomatitis virus (VSV), a common livestock pathogen, into which an Ebola viral coat protein has been introduced. With funding from the US DOD’s Defense Threat Reduction Agency (DTRA), Newlink Genetics Corp has licensed an Ebola vaccine candidate developed by researchers at the Public Health Agency of Canada and are poised to begin human clinical trials before the end of the month of August 2014. Newlink is working with manufacturers to scale up production of the drug so that tends of thousands of doses could be available within a few months.

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interactions between the different types of DNA, RNA and protein biosynthesis as well as learning how these interactions are regulated.

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August 30, 2014, 10:21 am

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August 30, 2014, 6:00 pm

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August 31, 2014, 1:53 am

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Sequence of human genome

July 7, 2014, 6:48 am

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Question on Telomeres

July 8, 2014, 7:03 am

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I understand the general concept of Telomeres buffering the genetic sequence, and that they degrade over time with each division of the cell. My question is: What creates and/or repairs the Telomeres in sex cells and related cells, to ensure a full amount of cell divisions for the resultant zygote? Is it Telomerase, and if so, why is the process specific to only the sexual reproduction process? If this didn't happen, wouldn't the genetic code of even sex cells degrade with every iteration meiosis? I know sex cells only divide once, however after many generations? wouldn't their DNA degrade without the protection provided by Telomeres?

I apologize for the bulk of questions, I am only trying to clarify my exact question, so as to avoid general answers that may be found online with a quick web query.

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Oral bacteria and increased atherosclerosis risk

July 15, 2014, 12:29 am

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A new study supports the idea that good oral hygiene can help protect against cardiovascular disease risk. The oral anaerobic bacteria Porphyromonas gingivalis can evade host immune recognition and increase systemic inflammation and increased atherosclerosis risk by altering a surface molecule called lipid A so that it blocks activation of a key host immune receptor called toll-like receptor 4 (TLR-4). This results in an attenuated production of anti-bacterial inflammatory cytokines by the host and allows the bacteria to survive in macrophages, host cells that normally ingest and kill bacteria. These are the main findings of a new paper in the journal PLoS Pathogens from researchers in Boston University School of Medicine and the University of Washington.

P. gingivalis is an oral gram negative bacteria that causes local inflammation, resulting in destruction of tissues that support the teeth and resorption of bone. However, it is also associated with increased systemic inflammation with increased risk of diseases including diabetes and cardiovascular disease. It has been detected in atherosclerotic lesions in humans and has been shown to increase atherosclerosis in animal models. In the current study, the researchers sought to determine the mechanism behind this increased systemic inflammation and atherosclerosis. The results indicated that the mechanism behind systemic inflammation differed from that underlying local inflammation.

In common with other gram-negative bacteria, P. gingivalis expresses a protein called lipid A, which is the part of the lipopolysaccharide in the bacterial cell wall recognised by the key host TLR-4 immune receptor. Recognition of lipid A by TLR-4 initiates an immediate immune response characterised by release of pro-inflammatory cytokines and bacterial ingestion and killing by host macrophages. However, many bacteria have evolved strategies to modify lipid A and evade host recognition via TLR-4. P. gingivalis produces a number of modified lipid A structures, some of which are antagonistic to TLR-4 or induce no response from the receptor. The current study shows that the increased systemic inflammation and atherosclerosis induced by P. gingivalis involves the modified lipid A structures.

The research team used modified strains of P. gingivalis incorporating distinct lipid A versions, one of which activated TLR-4 (agonist) and one of which inhibited TLR-4 activation (antagonist). They used these P. gingivalis strains to infect a mouse model which was prone to atherosclerosis. The results indicated that use of the antagonist P. gingivalis strain resulted in reduced production of pro-inflammatory mediators and bacterial survival in macrophages with chronic vascular inflammation. By contrast, infection with the agonist P. gingivalis strain increased the production of proinflammatory mediators and macrophage killing of bacteria. The results also indicated that lipid A variations had no impact on the local response leading to oral tissue and bone damage, indicating that this is mediated by a separate mechanism.

The researchers conclude, “P gingivalis modifies its lipid A structure in order to evade host defenses and establish chronic infection leading to persistent systemic low-grade inflammation…uniquely among gram-negative pathogens, P. gingivalis evasion of TLR4-mediated host immunity results in progression of inflammation at a site that is distant from local infection by gaining access to the vasculature.”

Source

Slocum C, Coats SR, Hua N, Kramer C, Papadopoulos G, et al. (2014) Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation. PLoS Pathog 10(7): e1004215. doi:10.1371/journal.ppat.1004215; http://dx.plos.org/10.1371/journal.ppat.1004215

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Xpert MTB/RIF diagnostic test rollout could reduce TB incidence in India

July 15, 2014, 2:11 pm

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A new study suggests that the Xpert MTB/RIF, a recently implemented tuberculosis (TB) test, would be effective in helping control the TB epidemic in India. However, the mathematical model described in the study of tuberculosis transmission, care-seeking behaviour, and diagnostic/treatment practices shows that such improvements would depend on a major overhaul of the implementation strategy currently in place for TB diagnosis and treatment, involving both the public and private sectors. The study is published today in the journal PLoS Medicine, from researchers in the USA, India and Canada, led by Dr David Dowdy of Johns Hopkins University.

Tuberculosis (TB) remains a significant health problem internationally, causing 1.4 million deaths per year. Over one quarter of these occur in India, prompting the country to announce a goal of universal access to quality TB diagnosis and treatment. This goal is complicated by the complex health care system in India, with many people depending on private providers with no formal medical training or with some training in allopathic or non-allopathic training. While a Revised National Tuberculosis Control Programme (RNTCP) has made progress over the last 15 years in improving TB control in the public sector, many people turn to the public sector only as a last resort. There is a need to extend the current narrow implementation strategy to include the private sector and improve referral networks between the private and public sectors. In this context, combined with improved funding, the Xpert MTB/RIF, a recently implemented tuberculosis (TB) test, has the potential to control the TB epidemic in India.

Xpert MTB/RIF is a new TB diagnostic test with improved sensitivity compared to other currently used diagnostic tests, including the sputum smear microscopy test commonly used in the public sector in India and the even lower-performing tests used in the private sector, such as antibody or interferon-gamma release assays. It is a molecular test that uses semi-automated PCR to detect mycobacterial DNA. It has the added advantage of being able to detect resistance to the most effective TB antibiotic rifampicin, due to inclusion of specific primers. However, the cost of Xpert MTB/RIF is substantial and resource constraints currently dictate that the RNTCP is implementing this test chiefly as a rapid drug susceptibility testing method in vulnerable adults and children with HIV or at high risk of multi-drug resistant TB, rather than as a rapid and sensitive diagnostic test for TB.

In the current study, the research team constructed a mathematical model of tuberculosis transmission, care-seeking behaviour and diagnostic/treatment practices in India to predict the impact on TB incidence if six different rollout strategies were to be implemented. The most effective predicted scenario envisaged adding Xpert MTB/RIF access for 20% of all individuals with TB symptoms seeking diagnosis in the public sector and 20% of individuals seeking care from qualified private practitioners. Compared to the current implementation strategy, this scenario would be predicted to reduce TB incidence by 14.1%. However, it would entail substantial cost as it would require more than 2,200 Xpert machines and reliable treatment referral. It is worth noting that a scenario envisaging encouragement of informal private providers to refer suspected TB cases to the public sector for diagnosis using currently available tests predicted a greater impact on TB incidence than if the Xpert system were scaled up only within the public sector.

While the authors acknowledge that their findings must be interpreted in the light of uncertainties in the assumptions made in the model, they are confident that: “Xpert [MTB/RIF] ... could substantially reduce the burden of TB disease due to poor diagnosis in India; however, this impact depends not only on the accuracy of the test, but also on the behavior of both patients and providers, their level of access to new tools, and quality TB treatment following diagnosis.”
The authors conclude: “any Xpert [MTB/RIF] rollout strategy must also consider the complex health-care infrastructure into which the test is being rolled out. To achieve maximum impact of novel diagnostics, India should engage the private sector, improve quality of care across all sectors, and dramatically increase resources.”

Sources

Salje H, Andrews JR, Deo S, Satyanarayana S, Sun AY, et al. (2014) The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model. PLoS Med 11(7): e1001674. doi:10.1371/journal.pmed.1001674;
http://www.plosmedicine.org/article/info...ed.1001674

News source: PLoS Medicine

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July 19, 2014, 2:28 am

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Genetic basis of schizophrenia: new insights

July 21, 2014, 11:39 pm

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A new study sheds new light on the genetic underpinnings of schizophrenia. The study, from the international, multi-institution Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) is published today in the journal Nature. It involved a genome-wide association study (GWAS) on 36,989 schizophrenia cases and 113,075 controls. This represents the largest GWAS to date in any psychiatric illness. 128 independent associations were identified over 108 specific locations of the human genome associated with schizophrenia risk; 83 of these had not been previously reported in schizophrenia risk.

Schizophrenia is a heritable disorder present in about 1:100 of the population. It features hallucinations, delusions, and disordered thinking and exacts an enormous human and financial cost. Current therapies mainly tackle the psychosis element; there are no effective treatments for the cognitive elements of the disease. Recent research suggests that the genetic basis of schizophrenia is highly complex, involving interaction of many genes. The current study, using a total of 55 datasets from more than 40 different contributors, confirmed and built on this knowledge as a result of years of work from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. One of the contributors, Dr Jo Knight of Canada's Centre for Addiction and Mental Health (CAMH) explains: "Large collaborative efforts such as this one are needed to identify genes that influence complex disorders…The result is a major advance in understanding the genetic basis of brain functioning in schizophrenia."

The study identified the importance of genes expressed in brain tissue, particularly those related to neuron functioning and of signalling via synapses. They included genes implicated in control of synaptic plasticity, which is crucial in learning and memory, and pathways in the cells receiving the signal. A smaller number of immune system genes were also identified, supporting hypotheses concerning links between schizophrenia and immunity. While many of these findings point to new insights into the aetiology of schizophrenia, associations at the dopamine receptor DRD2 and many genes associated with glutamatergic neurotransmission point to molecules already known to have potential therapeutic relevance to schizophrenia.

Senior author Dr Michael O’Donovan of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine concludes: "The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases…The wealth of new findings has the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years."

Sources

Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature (2014)doi:10.1038/nature13595

Press release: CAMH; available at http://www.eurekalert.org/pub_releases/2...072114.php [Accessed 22 July 2014]

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International Bioprinting Congress: DeCoster presentation on 3D and 2D advances

July 21, 2014, 11:59 pm

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The International Bioprinting Congress taking place between July 24-25 at the Biopolis Research and Development Center in Singapore will feature leading international scientists who will share insights into the latest developments and techniques in 3D bioprinting. Advances that will be featured will include additive manufacturing of tissues and biofabrication, scaffolds and biomaterials for tissue engineering, biological laser printing, biological inkjet printing, and research into achieving synergy by fusion of bio-additive and micro manufacturing.

Among the invited speakers will be Dr. Mark DeCoster, the James E. Wyche III Endowed Professor in Biomedical Engineering at Louisiana Tech University. Dr DeCoster is an eminent scientist who has published 60 peer-reviewed papers, generating over 1,750 citations. He will present a lecture titled, “Bioprinting interfaces for 2D and 3D cell and tissue models.” This will highlight the work of Dr DeCoster’s lab in developing a novel, matrix-free method for generating 3D cell spheroids. This combines knowledge from bioprinting methods on 2D surfaces to link 3D cellular structures.

Dr DeCoster explains the potential for 3D bioprinting techniques in biology and medicine: “The cells of our bodies exist in both a three dimensional (3D) environment, which is rounder, as well as places that are more two dimensional (2D) or flattened…What is so new and exciting about 3D printers in the biomedical sciences and engineering is that we can now enable our imagination to convert a good idea into something that is printable and testable in 3D, and could have significant impacts on human health…3D printers are now replicating materials that are compatible with biology and medicine such as delivery of drugs to fight off cancer or growth-promoting materials that can be used for tissue engineering to heal a wound or repair a damaged part of the body.”

Dr DeCoster’s lab uses 3D printers to generate cell-compatible building blocks which they then use to study cell groups in both 3D and 2D. Dr DeCoster clarifies the relevance of this: “We feel this is important because we need to understand how to put cells together to grow better tissues or repair them, and also to understand how damaged or diseased cells behave…We need to understand both the 2D and 3D environments since different parts of the body use different materials to function, and this complexity of materials will most likely also be needed in bioprinting…In my presentation at the International Bioprinting Congress, I look forward to sharing the research we’re doing at Louisiana Tech on how normal cells of the brain as well as cancer cells (such as in brain tumors), can be studied using materials from 3D printers and how we combine those materials with cells.”

Source:

Press release: Louisiana Tech University; available at http://news.latech.edu/2014/07/21/biomed...singapore/ [Accessed 22 July 2014]

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Let's Talk about Knockdown!

September 1, 2014, 8:00 pm

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