Sequence variation is investigated in two different contexts: protein domains of unknown function or DUFs, and virus-host protein-protein interactions. In Chapter I, an integrative Bioinformatics approach is used to elaborate the phylogenetic distribution, extent of structural knowledge, and size characteristics of DUFs, as well as to infer essentiality and possible functions. DUFs are often found to be conserved across all kingdoms of life, although they are particularly common among bacteria, where we report 238 essential DUFs or eDUFs. Unlike non-DUFs, essentiality for DUFs does not appear to be related to conservation. Chapter II presents a methodology for investigating essential interactions of eDUFs using systematic mutation of interface residues, which we propose will aid in solving the function of eDUFs. In Chapter III, a computational pipeline for extracting essential protein-protein interactions between a virus and its host (HIV-1 - human), and identifying sequence variants in host ...

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...

By Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton and Michael B. Zwick ...

Delineation of the intricacies of protein function from macromolecular structure constitutes a continual obstacle in the study of cell and pathogen biology. Structure-based phylogenetic analysis has emerged as a powerful tool for addressing this challenge, allowing the detection and quantification of conserved architectural properties between proteins, including those with low or no detectable sequence homology. With a focus on viral protein structure, we highlight how a number of investigations have utilized this powerful method to infer common functionality and ancestry.

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This is a list of changes made recently to pages linked from a specified page (or to members of a specified category). Pages on your watchlist are bold. ...

ATLANTA, Feb. 01, 2017 (GLOBE NEWSWIRE) -- Aviragen Therapeutics, Inc. (Nasdaq:AVIR), a company focused on the discovery and development of the next generation of direct-acting antivirals to treat infections that have limited therapeutic options, today announced top-line data from its double-blind, placebo-controlled Phase 2a study of BTA585 ...

They are simply a self-fulfilling prophecy. You get back what you built into the model.. The point of models like these are not to prove something by themselves. Instead, they allow you to identify simpler propositions to prove, which, if true, would establish that the model is right.. For example, if the predominant way that an independent chiefdomship arises without a war is as a result of the death of chief, then we know that this kind of event will have big implications for the dynamics (a non-obvious result). Then, we can dig through the best available datat in chiefdomship societies that are documented historically to determine what historically did cause independent chiefdomships to arise. If our model assumption is supported, we get a lot more bang for our buck out of that factual discovery than we would otherwise.. Similar garbage in, garbage out criticisms can be made of a recent contagion model of terrorism, where the key variable is the extent to which a harsh suppression of a ...

For decades, most of molecular biology was driven by the central dogma in which the phenotype is defined by the genotype following a fully deterministic point of view. However, during the last 10 years, a wealth of studies has demonstrated that a given genotype can generate multiple phenotypes in identical environmental conditions, mainly because of the inherently probabilistic nature of the transcription process. It has also been shown that cells can tune this variability at the molecular level. Although previously described as a useless noise, stochastic gene expression has now been shown by many authors to be an essential part of diverse biological processes. Chromatin dynamics having a central role in higher eukaryotes, we decided to investigate its involvement in the generation and control of stochasticity in gene expression (SGE). Our experiments reveal that the chromatin environment of a gene plays an important role in regulating SGE. Indeed, we find that histone acetylation and DNA

Regulatory genes called small RNAs (sRNAs) are known to play critical roles in cellular responses to changing environments. For several bacterial sRNAs, regulation is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs). The nonlinearity inherent in this regulatory scheme implies that exact analytical solutions for the corresponding stochastic models are intractable. Based on the mapping of the master equation to a quantum evolution equation, we use the variational method (introduced by Eyink) to analyze a well-studied stochastic model for regulation by sRNAs. Results from the variational ansatz are in excellent agreement with stochastic simulations for a wide range of parameters, including regions of parameter space where mean-field approaches break down. The results derived provide new insights into sRNA-based regulation and will serve as useful inputs for future studies focusing on the interplay of stochastic gene expression and regulation by sRNAs ...

-final study leading to full Canadian license for the vaccine- BELLEVILLE, ON, May 5 /PRNewswire-FirstCall/ - Bioniche Life Sciences Inc.

One of the surprising lessons I learned working on Digital Minimalism is that when it comes to reforming your relationship with your devices, successful outcomes are less about deciding to stop harmful digital behaviors than they are about deciding to start committing to meaningful analog alternatives. If you simply resolve to quit social media, and […]

At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals w

Tiny House Movement, a Flipboard topic with the latest stories powered by top publications and the best from the Flipboard community

WCCT uses the CPT method for PBMC isolation when conducting human challenge studies at their Viral Challenge facility in Costa Mesa, CA.

New preventative nasal spray treatment that could protect people from COVID-19 infection and prevent transmission announced Novel therapy developed by Australian biotech company, Ena Respiratory, shown to significantly reduce COVID-19 virus levels in the nose and throat, in a gold-standard animal studyReduced COVID-...

Research from Study Paper: VHA Managerial Challenge In recent times, the United States Division of Veterans Affairs offers experienced significant...

In 2008, colorectal cancer (CRC) was the fifth most prevalent cancer in the USA accounting for 149,800 new cases and the second most deaths, ~49,000. Progressio...

Stochastic nature of gene transcription is widely known and its contribution to heterogeneity of cellular responses to various stimuli is well recognized.

I am theoretical physicist by training. However, I early jumped into biology to study genome evolution and regulatory network structure in bacteria and I obtained a PhD in Bioinformatics form the University of Basel. During my postdoc training at the EPFL I worked on stochastic gene expression in single mammalian cells. Afterwards, I started my own research group at the University of Edinburgh and recently moved to the IGBMC.. Research Interests. The main research activity in my group is to develop stochastic and biophysical models of eukaryotic gene regulation. Our work lays at the interface between bioinformatics and biophysics combining tools and methods from both fields to develop mechanistic models of gene regulation based on both large-scale genome-wide data and single-cell imaging data. Some of our ongoing projects are:. ...

ETEC controlled human infection volunteer challenge studies. Samples for blood group analysis were obtained from a convenience sample of 106 human volunteers from 4 prior independent controlled human infection model ETEC challenge studies conducted at the Johns Hopkins Center for Immunization Research (ClinicalTrials.gov NCT01739231, NCT01060748, NCT00844493, and NCT01922856). All volunteers were experimentally infected with 1 to 2 × 107 colony-forming units of the EtpA-expressing ETEC strain H10407. Subjects in these studies were treated with antibiotics once they met previously defined endpoint criteria (summarized in Supplemental Table 1) or at 120 hours after inoculation to clear their infections. Additional details of the of the study design are included in the Supplemental Methods.. Glycan-array screening. Glycan arrays containing 411 separate features were fabricated as previously reported, except for the addition of a washable fluorescent dye, the free acid of DyLight 649 (0.7 μg/ml, ...

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details ...

Researchers are set to explore a human challenge study with the virus that causes COVID-19, the first such study anywhere in the world. The Human Challenge Programme is a partnership ...

Researchers are set to explore a human challenge study with the virus that causes COVID-19, the first such study anywhere in the world. The Human Challenge Programme is a partnership ...

Forty-six strains of Japanese encephalitis (JE) virus from a variety of geographic areas in Asia were examined by primer-extension sequencing of the RNA template. A 240 nucleotide sequence from the pre-M gene region was selected for study because it provided sufficient information for determining genetic relationships among the virus isolates. Using 12% divergence as a cutoff point for virus relationships, the 46 isolates fell into three distinct genotypic groups. One genotypic group consisted of JE virus isolates from northern Thailand and Cambodia. A second group was composed of isolates from southern Thailand, Malaysia, Sarawak and Indonesia. The remainder of the isolates, from Japan, China, Taiwan, the Philippines, Sri Lanka, India and Nepal, made up a third group. The implications of these findings in relation to the epidemiology of JE are discussed. Results of this study demonstrate that the comparison of short nucleotide sequences can provide insight into JE virus evolution, transmission and,

Historical Introduction - Foundations of Synthetic Biology- Biochemistry & Molecular Biology, Gene expression and gene regulation, Signaling, Metabolism, Nonlinear dynamics, Stochastic gene expression - Technology for Synthetic Biology: Biochemical tools Cloning, Recombineering, Genome engineering & editing, Sequencing, Rational design vs. Evolution, Microfluidic techniques - In vitro and cell-free synthetic biology: Bionanoscience, Cell-free biotechnology, Artificial cells, Artificial life - Minimal cells: Reduced genomes, orthogonal chemistries, expanding the genetic code - Synthetic regulatory circuits: Bacterial computation, Memory, Bacterial communication, pattern formation, etc., RNA synthetic biology Engineering issues, metabolic engineering and applications will follow in part ...

Nucleic Acid: Plasmid for expression of the LCMV S-segment with heterologous arenavirus GP - Machupo (Expression plasmid, Diagnostic reagent, Derived product, Nucleic Acid, Cloned nucleic acid)

Talks on nuclear arms reductions could trigger a breakthrough in Russian-American relations in the near future, says Joseph Ciricione, a U.S. arms control expert.

Shop Squirrel monkey agnoprotein ELISA Kit, Recombinant Protein and Squirrel monkey agnoprotein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.

Hay fever is a complicated condition to assess, and mimic in a clinical setting. The researchers used a single allergy challenge, applied to the volunteers nasal passage, to provide a standard, reproducible test to help ensure all the subsequent results are comparable. In the real world hay fever is usually triggered by longer term exposure to the allergen, variable in strength and timing over a period of days or weeks. The IFR researchers are now exploring the possibility of carrying out a seasonal study to investigate whether the changes in the nasal mucosa seen in this single challenge study relate to changes in hay fever symptoms triggered by a more realistic natural exposure to pollen ...

Alongside the flood of anti-national ID comments that hit the Department of Homeland Security (DHS) this week, theres some other good news in the fight to stop the REAL ID Act. The states rebellion against this unfunded mandate continues to thrive, as Colorado became the eighth state to...

10/23/15: The Capitals show impressive puck movement on the rush as Evgeny Kuznetsov finishes off the play with a goal on Anders Nilsson

The relationships between cancer and stemness have a long history that is traced here. From the mid-19th century when the first theory on the embryonic origin of cancer was formulated to works on embryonal carcinoma cells in the mid-20th century, many steps have been crossed leading to the current cancer stem cell theory postulating that tumor growth is supported by a small fraction of the tumoral cells that have stem-like properties. However, in the last fifteen years, many works regularly encourage us to revise the concept of cancer stem cell. This article mentions key results that lead to a new perspective where cancer stem cells are primarily seen as cells exhibiting increased epigenetic plasticity and increased gene expression variability. This perspective suggests new therapeutical interventions consisting in stabilizing gene expression to control cancer cell proliferation and prevent stochastic gene expression variations that could lead to therapeutic resistance.

Mutant polioviruses (PV) have been previously found to be capable of establishing persistent infections in HEp-2c cells. Together, two amino acid substitutions in the viral capsid of a type 3 poliovirus (PV-3), at positions VP213 and VP1290, are sufficient to confer the persistent phenotype to a normally lytic virus. When susceptible cells are infected, the double mutant T7L+2L 131N290 undergoes unique conformational changes in the capsid, modifying its sedimentation coefficient from 160S to 147S. In the present study, we have further investigated mutant PV decapsidation and, in particular, the effect of each determinant independently. Our results indicate that the novel 147S form was also generated by a mutant carrying only the determinant 1N290. This form was not produced as a result of inherent capsid instability and it was generated only upon specific PV-host cell interactions. The second viral determinant, 2L13, also modified receptor-induced conformational changes, although differently from 1N290.

Open Orphan (AIM: ORPH), a rapidly growing specialist clinical research organisation (CRO) and world leader in vaccine and antiviral testing using human challenge clinical trials, announces that hVIVO, a subsidiary of Open Orphan plc, has signed a £5.7m contract with a specialist biotechnology company developing therapeutics for respiratory viral infections, to test its antiviral product using the hVIVO Influenza human challenge study model.. The human challenge study is expected to commence in Q1 2022 and will be conducted at hVIVOs state-of-the-art facilities in London. The Company expects the revenue from the contract to be recognised across 2021 and 2022.. The clients influenza antiviral product has demonstrated effectiveness in animal preclinical models of respiratory viruses and has several clinical and commercial advantages with respect to convenience, resistance, durability and compatibility when compared to similar products.. The Company expects to sign more contracts in this area as ...