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Intrinsic map dynamics exploration for uncharted effective free-energy landscapes [Applied Mathematics]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
We describe and implement a computer-assisted approach for accelerating the exploration of uncharted effective free-energy surfaces (FESs). More generally, the aim is the extraction of coarse-grained, macroscopic information from stochastic or atomistic simulations, such as molecular dynamics (MD). The approach functionally links the MD simulator with nonlinear manifold learning techniques....

Hidden electrostatic basis of dynamic allostery in a PDZ domain [Biophysics and Computational Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Allosteric effect implies ligand binding at one site leading to structural and/or dynamical changes at a distant site. PDZ domains are classic examples of dynamic allostery without conformational changes, where distal side-chain dynamics is modulated on ligand binding and the origin has been attributed to entropic effects. In this work,...

Population-genomic inference of the strength and timing of selection against gene flow [Evolution]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
The interplay of divergent selection and gene flow is key to understanding how populations adapt to local environments and how new species form. Here, we use DNA polymorphism data and genome-wide variation in recombination rate to jointly infer the strength and timing of selection, as well as the baseline level...

1T-TaS2 as a quantum spin liquid [Physics]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
1T-TaS2 is unique among transition metal dichalcogenides in that it is understood to be a correlation-driven insulator, where the unpaired electron in a 13-site cluster experiences enough correlation to form a Mott insulator. We argue, based on existing data, that this well-known material should be considered as a quantum spin...

qSVA framework for RNA quality correction in differential expression analysis [Biophysics and Computational Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
RNA sequencing (RNA-seq) is a powerful approach for measuring gene expression levels in cells and tissues, but it relies on high-quality RNA. We demonstrate here that statistical adjustment using existing quality measures largely fails to remove the effects of RNA degradation when RNA quality associates with the outcome of interest....

Sex-specific early survival drives adult sex ratio bias in snowy plovers and impacts mating system and population growth [Population Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Adult sex ratio (ASR) is a central concept in population biology and a key factor in sexual selection, but why do most demographic models ignore sex biases? Vital rates often vary between the sexes and across life history, but their relative contributions to ASR variation remain poorly understood—an essential step...

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States [Medical Sciences]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4,...

Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells [Biochemistry]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family...

Monte Carlo sampling for stochastic weight functions [Applied Mathematics]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Conventional Monte Carlo simulations are stochastic in the sense that the acceptance of a trial move is decided by comparing a computed acceptance probability with a random number, uniformly distributed between 0 and 1. Here, we consider the case that the weight determining the acceptance probability itself is fluctuating. This...

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria [Biochemistry]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes...

Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics [Biophysics and Computational Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Multiple biological processes involve the stretching of nucleic acids (NAs). Stretching forces induce local changes in the molecule structure, inhibiting or promoting the binding of proteins, which ultimately affects their functionality. Understanding how a force induces changes in the structure of NAs at the atomic level is a challenge. Here,...

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity [Microbiology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-d-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide....

Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions [Biochemistry]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1–ISD11–ACP (SDA) complex forms the core of the iron–sulfur (Fe–S) assembly complex and associates with assembly proteins ISCU2,...

Structural characterization of the Rabphilin-3A-SNAP25 interaction [Biophysics and Computational Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and...

Redox-dependent interaction between thaumatin-like protein and {beta}-glucan influences malting quality of barley [Plant Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Barley is the cornerstone of the malting and brewing industry. It is known that 250 quantitative trait loci (QTLs) of the grain are associated with 19 malting-quality phenotypes. However, only a few of the contributing genetic components have been identified. One of these, on chromosome 4H, contains a major malting...

SUPERMAN prevents class B gene expression and promotes stem cell termination in the fourth whorl of Arabidopsis thaliana flowers [Plant Biology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
The molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. The SUPERMAN gene is required for proper specification of the boundary between stamens in whorl 3 and carpels in...

Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells [Pharmacology]

PNAS Early Edition Articles - Tue, 06/20/2017 - 09:14
Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches...

Skeptic Challenges Climate Science Education

Climate Depot - Tue, 06/20/2017 - 07:22
06/19/2017 | By Kennedy Maize Veteran global warming gadfly David Wojick is mounting a challenge to the way climate science is being taught in our schools, and raising money online for his venture. At the same time, Environmental Protection Agency chief Scott Pruitt says he wants to mount teams to debate climate science, according to the Washington [...]

New ‘Consensus’: Climate models failed to predict nearly 20 year long ‘hiatus’ or ‘pause’

Climate Depot - Tue, 06/20/2017 - 07:06
By Michael Bastasch and Ryan Maue A scientific consensus has emerged among top mainstream climate scientists that “skeptics” or “lukewarmers” were not long ago derided for suggesting — there was a nearly two-decade long “hiatus” in global warming that climate models failed to accurately predict or replicate. A new paper, led by climate scientist Benjamin Santer, [...]

Experts Published A Scathing Rebuttal To The Left’s Favorite Green Energy Study

Climate Depot - Tue, 06/20/2017 - 07:00
By Michael Bastasch A group of researchers have published a scathing rebuttal to a 2015 report claiming the U.S. could run on 100 percent green energy, which they say suffered from “significant shortcomings.” The 2015 study led by Stanford University professor Mark Jacobson claimed wind turbines, solar power and hydroelectric dams could power the entire [...]
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