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Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History

"The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history."

 

Ex Africa, semper aliquid novi...or old, in this case!

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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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This topic is a collaborative effort:

This topic is a collaborative effort: | Virology and Bioinformatics from Virology.ca | Scoop.it
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SigHunt: horizontal gene transfer finder optimized for eukaryotic genomes

SigHunt: horizontal gene transfer finder optimized for eukaryotic genomes | Virology and Bioinformatics from Virology.ca | Scoop.it

Motivation: Genomic islands (GIs) are DNA fragments incorporated into a genome through horizontal gene transfer (also called lateral gene transfer), often with functions novel for a given organism. While methods for their detection are well researched in prokaryotes, the complexity of eukaryotic genomes makes direct utilization of these methods unreliable, and so labour-intensive phylogenetic searches are used instead.

Results: We present a surrogate method that investigates nucleotide base composition of the DNA sequence in a eukaryotic genome and identifies putative GIs. We calculate a genomic signature as a vector of tetranucleotide (4-mer) frequencies using a sliding window approach. Extending the neighbourhood of the sliding window, we establish a local kernel density estimate of the 4-mer frequency. We score the number of4-mer frequencies in the sliding window that deviate from the credibility interval of their local genomic density using a newly developed discrete interval accumulative score (DIAS). To further improve the effectiveness of DIAS, we select informative 4-mers in a range of organisms using the tetranucleotide quality score developed herein. We show that the SigHunt method is computationally efficient and able to detect GIs in eukaryotic genomes that represent non-ameliorated integration. Thus, it is suited to scanning for change in organisms with different DNA composition.

 
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What the Tamiflu saga tells us about drug trials and big pharma

What the Tamiflu saga tells us about drug trials and big pharma | Virology and Bioinformatics from Virology.ca | Scoop.it
Ben Goldacre: We now know the government's Tamiflu stockpile wouldn't have done us much good in the event of a flu epidemic. But the secrecy surrounding clinical trials means there's a lot we don't know about other medicines we take
Chris Upton + helpers's insight:

It's sad that this causes distrust that spills over to vaccines -  which WORK!

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Drawing a Ring Around Antiviral Immunity | HMS

Drawing a Ring Around Antiviral Immunity | HMS | Virology and Bioinformatics from Virology.ca | Scoop.it
@harvardmed & @BostonChildrens: Drawing a Ring Around Antiviral Immunity http://t.co/OF3EUh4WBr #Ubiquitin #cancer #Immunology

Via Gilbert Faure au nom de l'ASSIM
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How Harmless Bacteria Quickly Turned Into a Flesh-Eating Monster

How Harmless Bacteria Quickly Turned Into a Flesh-Eating Monster | Virology and Bioinformatics from Virology.ca | Scoop.it
Genetic study reveals that just four changes gave Streptococcus the ability to cause deadly disease.
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Is US biomedical research heading for a breakdown?

Is US biomedical research heading for a breakdown? | Virology and Bioinformatics from Virology.ca | Scoop.it
Senior researchers who helped build the system now think it's unsustainable.
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Ana Sanchez's curator insight, April 16, 2:41 PM

A big piece of food for thought

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Proteomic analysis at the subcellular level for host targets against influenza A virus (H1N1). - Antiviral Res. 2013

Influenza viruses (IVs) trigger a series of intracellular signaling events and induce complex cellular responses from the infected host cell. Accumulating evidence suggests that host cell proteins play an essential role in viral propagation and represent novel antiviral therapeutic targets. Subcellular proteomic technology provides a method for understanding regional differences at the protein level. The present study, which utilized subcellular proteomic technology, aimed to identify host cell proteins involved in influenza virus (HIN1) infection. Two-dimensional gel electrophoresis (2-DE) combined with mass spectrum (MS) was performed on protein extracts from the nuclei, cytoplasm, and mitochondria of infected and control human lung epithelial cells (A549). In total, 112 differentially expressed protein molecules were identified; 80 protein spots were successfully validated using MS. The differential expression of ISG15, MIF, PDCD5, and UCHL1 was confirmed by western blot. Furthermore, antisense oligodeoxyribonucleotide (ODN) targeting ISG15, MIF, PDCD5, and UCHL1 significantly mitigated HIN1 propagation, cytopathic effects, vRNA by RT-qPCR, and rescued cell viability in A549 cells. Taken together, the differentially expressed proteins identified in this study might provide novel targets for anti-influenza drug development.

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Media Availability: Genetic Defect May Confer Resistance to Certain Viral Infections

Media Availability: Genetic Defect May Confer Resistance to Certain Viral Infections | Virology and Bioinformatics from Virology.ca | Scoop.it
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Positive selection and evolution of dengue type-3 virus in the Indian subcontinent - J Vector Borne Dis. 2013

AbstractBACKGROUND:

Dengue virus infection has recently taken endemic proportions in India with dengu type-3 (DEN-3) as a predominant serotype. In this study, we carried out the selection pressure analysis of three critical immunogenic regions of DEN-3. Phylogenetic analysis was then carried out on the positively selected genomic region in the DEN-3 virus strains isolated in the Indian subcontinent over a time span of 25 yr (1984-2008). Bayesian Markov chain Monte Carlo (MCMC) calculation of the substitution rate was carried out for the DEN-3 genotype-III sequences.

METHODS:

Sequences corresponding to the C-prM, E-NS1 and NS1 sequence regions of DEN-3 strains were taken for the positive selection analysis. The C-prM junction sequences were then used to construct a maximum likelihood (ML) phylogenetic tree. Substitution rates were also calculated under various models of population growth.

RESULTS:

It was found that codon 86, corresponding to a conserved arginine residue in a crucial T-cell epitope of the C-protein was under significant positive selection. The K86R substitution was found to exist in almost all the Indian strains isolated after 2004. The ML tree constructed from the C-prM junction sequences indicated that strains from the 2006 dengue incidences in Delhi, namely: 04/03/del2006, 05/03/del2006, and 06/03/del2006 were the most rapidly evolving. Substitution rates of a DEN-3 genotype-III sequences from the Indian subcontinent were found to be ~3.0 times higher than those reported from other parts of the world.

CONCLUSION:

Positive selection in the codon corresponding to R86 of the highly conserved surface C-protein is important in view of its occurrence in a T-cell epitope as well as its strict conservation in all the DEN strains. Phylogenetic analysis of the C-prM junction sequences showed that three strains of 2006 are rapidly evolving. These results were also supported by calculations of the substitution rates. Their significance in the expansion of viral epidemics requires to be investigated.

  
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Measles Outbreak Traced to Fully Vaccinated Patient for First Time

Measles Outbreak Traced to Fully Vaccinated Patient for First Time | Virology and Bioinformatics from Virology.ca | Scoop.it

Get the measles vaccine, and you won’t get the measles—or give it to anyone else. Right? Well, not always. A person fully vaccinated against measles has contracted the disease and passed it on to others. The startling case study contradicts received wisdom about the vaccine and suggests that a recent swell of measles outbreaks in developed nations could mean more illnesses even among the vaccinated.

 

When it comes to the measles vaccine, two shots are better than one. Most people in the United States are initially vaccinated against the virus shortly after their first birthday and return for a booster shot as a toddler. Less than 1% of people who get both shots will contract the potentially lethal skin and respiratory infection. And even if a fully vaccinated person does become infected—a rare situation known as “vaccine failure”—they weren’t thought to be contagious.

 

That’s why a fully vaccinated 22-year-old theater employee in New York City who developed the measles in 2011 was released without hospitalization or quarantine. But like Typhoid Mary, this patient turned out to be unwittingly contagious. Ultimately, she transmitted the measles to four other people, according to a recent report in Clinical Infectious Diseases that tracked symptoms in the 88 people with whom “Measles Mary” interacted while she was sick. Surprisingly, two of the secondary patients had been fully vaccinated. And although the other two had no record of receiving the vaccine, they both showed signs of previous measles exposure that should have conferred immunity.

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Pandemic Influenza: The Perpetual Challenge

Pandemic Influenza: The Perpetual Challenge | Virology and Bioinformatics from Virology.ca | Scoop.it
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DNA nanobots deliver drugs in living cockroaches - health - 08 April 2014 - New Scientist

DNA nanobots deliver drugs in living cockroaches - health - 08 April 2014 - New Scientist | Virology and Bioinformatics from Virology.ca | Scoop.it

It's a computer – inside a cockroach. Nano-sized entities made of DNA that are able to perform the same kind of logic operations as a silicon-based computer have been introduced into a living animal.

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rougeforfire's curator insight, April 10, 4:54 PM

WOOOO !!!! Nanobots are here !!

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Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages: Immunity

Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages: Immunity | Virology and Bioinformatics from Virology.ca | Scoop.it
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The Hallmarks of Cancer 8: Tumor-Promoting Inflammation | Guest Blog, Scientific American Blog Network

The Hallmarks of Cancer 8: Tumor-Promoting Inflammation | Guest Blog, Scientific American Blog Network | Virology and Bioinformatics from Virology.ca | Scoop.it
The Hallmarks of Cancer are ten underlying principles shared by all cancers. You can read the first seven Hallmarks of Cancer articles here. The eighth Hallmark ...
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DNA looping damage tied to HPV cancer, researcher discovers

DNA looping damage tied to HPV cancer, researcher discovers | Virology and Bioinformatics from Virology.ca | Scoop.it
Certain strains of human papillomavirus (HPV) are known to cause about five percent of all cancer cases, yet all the mechanisms aren't completely understood. Now, researchers have leveraged Ohio Supercomputer Center resources and whole-genome sequencing to identify a new way that HPV might spark cancer development -- by disrupting the human DNA sequence with repeating loops when HPV is inserted into host-cell DNA as it replicates.
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Warnings of 'catastrophic' Chikungunya epidemic; fears it could spread during the World Cup

Warnings of 'catastrophic' Chikungunya epidemic; fears it could spread during the World Cup | Virology and Bioinformatics from Virology.ca | Scoop.it
A team of French and Brazilian researchers warn that chikungunya virus is poised to invade, and become epidemic in the Americas according to research published ahead of print in the Journal of Virology.
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Now researchers can explore genomic data across space and time

Now researchers can explore genomic data across space and time | Virology and Bioinformatics from Virology.ca | Scoop.it
The figure above is part of a four-step procedure for the multiscale segmentation of genomic signals.

Via Pedro Fernandes
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DNA cube programmed for an exclusive reveal | Chemistry World

DNA cube programmed for an exclusive reveal | Chemistry World | Virology and Bioinformatics from Virology.ca | Scoop.it
Hydrogen bonds keeping the cube’s shape only unzip in the presence of a very specific trigger
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Running mothur from within iPython

Running mothur from within iPython | Virology and Bioinformatics from Virology.ca | Scoop.it
ipython-mothurmagic - IPython extension for running mothur commands in an IPython notebook
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Constraints from protein structure and intra-molecu... [Virology. 2014] - PubMed - NCBI

A major challenge for developing effective treatments for HIV-1 is the viruses' ability to generate new variants. Inter-strain recombination is a major contributor to this high evolutionary rate, since at least 20% of viruses are observed to be recombinant. However, the patterns of recombination vary across the viral genome. A number of factors influence recombination, including sequence identity and secondary RNA structure. In addition the recombinant genome must code for a functional virus, and expressed proteins must fold to stable and functional structures. Any intragenic recombination that disrupts internal residue contacts may therefore produce an unfolded protein. Here we find that contact maps based on protein structures predict recombination breakpoints observed in the HIV-1 pandemic. Moreover, many pairs of contacting residues that are unlikely to be disrupted by recombination are coevolving. We conclude that purifying selection arising from protein structure and intramolecular coevolutionary changes shapes the observed patterns of recombination in HIV-1.

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Correction: Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

Correction: Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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Are Bats Spreading Ebola Across Sub-Saharan Africa?

The first cases went unrecognized. Ebola had never been seen in Guinea before, so when people became ill with fever, muscle pain, vomiting, and diarrhea, health workers initially assumed Lassa fever or yellow fever—both endemic in the region—were to blame. No one put the pieces together until late March. By then, the virus had been spreading for months. Now, health workers are struggling to contain the outbreak, which has already killed more than 100 and has affected at least two neighboring countries. At the same time, scientists are combing the forests, and the genome of the virus itself, looking for clues to how this strain—well known in Central Africa—ended up so far west, and whether its spread suggests people in forested areas all across sub-Saharan Africa are at risk.

 

Ebola is not a complete stranger to West Africa. In the mid-1990s, two outbreaks hit chimpanzees in Taï National Park in the Ivory Coast, and one researcher studying the animals was infected. (She survived.) "We expected to find the Taï strain," says Sylvain Baize, a virologist at the Institut Pasteur in Lyon, France, who with his colleagues sequenced some of the first samples of the virus from Guinea. To their surprise, it turned out to be Ebola Zaire, the deadliest of the five known Ebola species.

 

"We have no idea how it's moved from Central Africa to Guinea," says primatologist Christophe Boesch of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. A leading suspect is fruit bats. In Central African rainforests, several species have shown evidence of infection with Ebola without getting sick. And at least one of the species, the little collared fruit bat, Myonycteris torquata, has a range that stretches as far west as Guinea. "We've always been very suspicious of bats," says William Karesh of EcoHealth Alliance in New York City, who studies the interactions among humans, animals, and infectious diseases.

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Ed Rybicki's curator insight, April 14, 6:50 AM

Thanks Torben Barsballe!

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BEAST 2: A Software Platform for Bayesian Evolutionary Analysis

BEAST 2: A Software Platform for Bayesian Evolutionary Analysis | Virology and Bioinformatics from Virology.ca | Scoop.it

We present a new open source, extensible and flexible software platform for Bayesian evolutionary analysis called BEAST 2. This software platform is a re-design of the popular BEAST 1 platform to correct structural deficiencies that became evident as the BEAST 1 software evolved. Key among those deficiencies was the lack of post-deployment extensibility. BEAST 2 now has a fully developed package management system that allows third party developers to write additional functionality that can be directly installed to the BEAST 2 analysis platform via a package manager without requiring a new software release of the platform. This package architecture is showcased with a number of recently published new models encompassing birth-death-sampling tree priors, phylodynamics and model averaging for substitution models and site partitioning. A second major improvement is the ability to read/write the entire state of the MCMC chain to/from disk allowing it to be easily shared between multiple instances of the BEAST software. This facilitates checkpointing and better support for multi-processor and high-end computing extensions. Finally, the functionality in new packages can be easily added to the user interface (BEAUti 2) by a simple XML template-based mechanism because BEAST 2 has been re-designed to provide greater integration between the analysis engine and the user interface so that, for example BEAST and BEAUti use exactly the same XML file format.

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Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus: Cell

Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus: Cell | Virology and Bioinformatics from Virology.ca | Scoop.it

Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.

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Leading virologists join together to address urgent viral threat

Causing victims to suffer severe fever and pain, chikungunya virus has reached the Caribbean and South America – and is predicted to soon cause outbreaks in the United States. For many years the virus has remained primarily in Africa, the Indian subcontinent and Southeast Asia. In response to the arrival of the virus in the Western Hemisphere, the Global Virus Network (GVN) announced today the formation of the GVN Chikungunya Task Force, comprised of top virologists from around the world.

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Scientists Generate 3D Structure for the Malaria Parasite Genome

Scientists Generate 3D Structure for the Malaria Parasite Genome | Virology and Bioinformatics from Virology.ca | Scoop.it

Abstract - "A research team led by a cell biologist at the University of California, Riverside has generated a 3D model of the human malaria parasite genome at three different stages in the parasite’s life cycle — the first time such 3D architecture has been generated during the progression of the life cycle of a parasite ."

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