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Measuring shared variants in cohorts of discordant siblings with applications to autism [Genetics]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:48
We develop a method of analysis [affected to discordant sibling pairs (A2DS)] that tests if shared variants contribute to a disorder. Using a standard measure of genetic relation, test individuals are compared with a cohort of discordant sibling pairs (CDS) to derive a comparative similarity score. We ask if a...

Potential high-Tc superconducting lanthanum and yttrium hydrides at high pressure [Physics]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
A systematic structure search in the La–H and Y–H systems under pressure reveals some hydrogen-rich structures with intriguing electronic properties. For example, LaH10 is found to adopt a sodalite-like face-centered cubic (fcc) structure, stable above 200 GPa, and LaH8 a C2/m space group structure. Phonon calculations indicate both are dynamically...

New perspective on spring vegetation phenology and global climate change based on Tibetan Plateau tree-ring data [Ecology]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Phenological responses of vegetation to climate, in particular to the ongoing warming trend, have received much attention. However, divergent results from the analyses of remote sensing data have been obtained for the Tibetan Plateau (TP), the world’s largest high-elevation region. This study provides a perspective on vegetation phenology shifts during...

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans [Biochemistry]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns...

Correction for Khan et al., Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease [Corrections]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
NEUROSCIENCE Correction for “Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease,” by Muzamil Majid Khan, Danilo Lustrino, Willian A. Silveira, Franziska Wild, Tatjana Straka, Yasmin Issop, Emily O’Connor, Dan Cox, Markus Reischl, Till Marquardt, Dittmar Labeit, Siegfried Labeit, Evelyne Benoit, Jordi Molgó, Hanns Lochmüller, Veit Witzemann, Isis...

Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting [Neuroscience]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD...

Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need [Neuroscience]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrtko/ko mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ...

Bacteria-mediated hypoxia functions as a signal for mosquito development [Developmental Biology]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Mosquitoes host communities of microbes in their digestive tract that consist primarily of bacteria. We previously reported that several mosquito species, including Aedes aegypti, do not develop beyond the first instar when fed a nutritionally complete diet in the absence of a gut microbiota. In contrast, several species of bacteria,...

G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis [Genetics]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse...

Tetrahydrobiopterin regulates monoamine neurotransmitter sulfonation [Biochemistry]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched “on” and “off” via transfer of the sulfuryl-moiety (–SO3) from PAPS (3′-phosphoadenosine 5′-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes—the human cytosolic...

A null model for microbial diversification [Evolution]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Whether prokaryotes (Bacteria and Archaea) are naturally organized into phenotypically and genetically cohesive units comparable to animal or plant species remains contested, frustrating attempts to estimate how many such units there might be, or to identify the ecological roles they play. Analyses of gene sequences in various closely related prokaryotic...

Mercury evidence for pulsed volcanism during the end-Triassic mass extinction [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
The Central Atlantic Magmatic Province (CAMP) has long been proposed as having a causal relationship with the end-Triassic extinction event (∼201.5 Ma). In North America and northern Africa, CAMP is preserved as multiple basaltic units interbedded with uppermost Triassic to lowermost Jurassic sediments. However, it has been unclear whether this...

Application of metabolic controls for the maximization of lipid production in semicontinuous fermentation [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Acetic acid can be generated through syngas fermentation, lignocellulosic biomass degradation, and organic waste anaerobic digestion. Microbial conversion of acetate into triacylglycerols for biofuel production has many advantages, including low-cost or even negative-cost feedstock and environmental benefits. The main issue stems from the dilute nature of acetate produced in such...

Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease [Pharmacology]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits...

Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the...

Global Sustainable Development priorities 500 y after Luther: Sola schola et sanitate [Sustainability Science]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Martin Luther succinctly summarized his theology in sola statements, such as sola scriptura, viewing the Bible (scriptura) as the only valid source of information about God rather than what he viewed as the extraneous, corrupting church doctrine of the time. As a secular side effect of this focus on individual...

Correction for Mattei et al., Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning [Corrections]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
PHYSIOLOGY Correction for “Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning,” by Alexandra L. Mattei, Mark L. Riccio, Frank W. Avila, and Mariana F. Wolfner, which appeared in issue 27, July 7, 2015, of Proc Natl Acad Sci USA (112:8475–8480;...

Efficient transport of tropospheric aerosol into the stratosphere via the Asian summer monsoon anticyclone [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
An enhanced aerosol layer near the tropopause over Asia during the June–September period of the Asian summer monsoon (ASM) was recently identified using satellite observations. Its sources and climate impact are presently not well-characterized. To improve understanding of this phenomenon, we made in situ aerosol measurements during summer 2015 from...

Efficient switching of mCherry fluorescence using chemical caging [Chemistry]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
Fluorophores with dynamic or controllable fluorescence emission have become essential tools for advanced imaging, such as superresolution imaging. These applications have driven the continuing development of photoactivatable or photoconvertible labels, including genetically encoded fluorescent proteins. These new probes work well but require the introduction of new labels that may interfere...

Intact piRNA pathway prevents L1 mobilization in male meiosis [Genetics]

PNAS Early Edition Articles - Mon, 06/19/2017 - 13:47
The PIWI-interacting RNA (piRNA) pathway is essential for retrotransposon silencing. In piRNA-deficient mice, L1-overexpressing male germ cells exhibit excessive DNA damage and meiotic defects. It remains unknown whether L1 expression simply highlights piRNA deficiency or actually drives the germ-cell demise. Specifically, the sheer abundance of genomic L1 copies prevents reliable...
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