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Amyloid fibrils shed membrane-active oligomers [Biochemistry]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Amyloid disorders cause debilitating illnesses through the formation of toxic protein aggregates. The mechanisms of amyloid toxicity and the nature of species responsible for mediating cellular dysfunction remain unclear. Here, using β2-microglobulin (β2m) as a model system, we show that the disruption of membranes by amyloid fibrils is caused by...

cIAPs prevent HBV clearance [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence and contribute to these outcomes need to be defined. Using an immunocompetent mouse model of chronic HBV infection, we identified some of...

Ctenophora is sister to all other animals [Evolution]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Elucidating relationships among early animal lineages has been difficult, and recent phylogenomic analyses place Ctenophora sister to all other extant animals, contrary to the traditional view of Porifera as the earliest-branching animal lineage. To date, phylogenetic support for either ctenophores or sponges as sister to other animals has been limited...

X-ray phase-contrast tomography with a CLS [Applied Physical Sciences]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Between X-ray tubes and large-scale synchrotron sources, a large gap in performance exists with respect to the monochromaticity and brilliance of the X-ray beam. However, due to their size and cost, large-scale synchrotrons are not available for more routine applications in small and medium-sized academic or industrial laboratories. This gap...

Covariation between pelvis, stature, and head [Anthropology]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Compared with other primates, childbirth is remarkably difficult in humans because the head of a human neonate is large relative to the birth-relevant dimensions of the maternal pelvis. It seems puzzling that females have not evolved wider pelvises despite the high maternal mortality and morbidity risk connected to childbirth. Despite...

cIAP drug antagonists clear HBV [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
We have shown that cellular inhibitor of apoptosis proteins (cIAPs) impair clearance of hepatitis B virus (HBV) infection by preventing TNF-mediated killing/death of infected cells. A key question, with profound therapeutic implications, is whether this finding can be translated to the development of drugs that promote elimination of infected cells....

Community ecology in a changing environment [Perspectives]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Community ecology and paleoecology are both concerned with the composition and structure of biotic assemblages but are largely disconnected. Community ecology focuses on existing species assemblages and recently has begun to integrate history (phylogeny and continental or intercontinental dispersal) to constrain community processes. This division has left a “missing middle”:...

Organogenesis in deep time [Evolution]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
The fossil record is a unique repository of information on major morphological transitions. Increasingly, developmental, embryological, and functional genomic approaches have also conspired to reveal evolutionary trajectory of phenotypic shifts. Here, we use the vertebrate appendage to demonstrate how these disciplines can mutually reinforce each other to facilitate the generation...

Elimination of an endosymbiotic organelle [Evolution]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Organelle gain through endosymbiosis has been integral to the origin and diversification of eukaryotes, and, once gained, plastids and mitochondria seem seldom lost. Indeed, discovery of nonphotosynthetic plastids in many eukaryotes—notably, the apicoplast in apicomplexan parasites such as the malaria pathogen Plasmodium—highlights the essential metabolic functions performed by plastids beyond...

GM3S SNAs reverse diabetic wound healing [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Spherical nucleic acid (SNA) gold nanoparticle conjugates (13-nm-diameter gold cores functionalized with densely packed and highly oriented nucleic acids) dispersed in Aquaphor have been shown to penetrate the epidermal barrier of both intact mouse and human skin, enter keratinocytes, and efficiently down-regulate gene targets. ganglioside-monosialic acid 3 synthase (GM3S) is...

TGF{beta}1 and diabetic nephropathy [Medical Sciences]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Nephropathy develops in many but not all patients with long-standing type 1 diabetes. Substantial efforts to identify genotypic differences explaining this differential susceptibility have been made, with limited success. Here, we show that the expression of the transforming growth factor β1 gene (Tgfb1) affects the development of diabetic nephropathy in...

Orai1 is indispensable for lactation [Physiology]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
The nourishment of neonates by nursing is the defining characteristic of mammals. However, despite considerable research into the neural control of lactation, an understanding of the signaling mechanisms underlying the production and expulsion of milk by mammary epithelial cells during lactation remains largely unknown. Here we demonstrate that a store-operated...

Sweet potato: A naturally transgenic food crop [Plant Biology]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Agrobacterium rhizogenes and Agrobacterium tumefaciens are plant pathogenic bacteria capable of transferring DNA fragments [transfer DNA (T-DNA)] bearing functional genes into the host plant genome. This naturally occurring mechanism has been adapted by plant biotechnologists to develop genetically modified crops that today are grown on more than 10% of the...

Modeling shocks in massive transportation systems [Statistics]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Public transportation systems are an essential component of major cities. The widespread use of smart cards for automated fare collection in these systems offers a unique opportunity to understand passenger behavior at a massive scale. In this study, we use network-wide data obtained from smart cards in the London transport...

Fluc channel block [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
The Fluc family is a set of small membrane proteins forming F−-specific electrodiffusive ion channels that rescue microorganisms from F− toxicity during exposure to weakly acidic environments. The functional channel is built as a dual-topology homodimer with twofold symmetry parallel to the membrane plane. Fluc channels are blocked by nanomolar-affinity...

NMR and neutron studies of proton transfer [Biochemistry]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Human carbonic anhydrase II (HCA II) uses a Zn-bound OH−/H2O mechanism to catalyze the reversible hydration of CO2. This catalysis also involves a separate proton transfer step, mediated by an ordered solvent network coordinated by hydrophilic residues. One of these residues, Tyr7, was previously shown to be deprotonated in the...

Causal effects of environment on stress reactivity [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Disruptions in stress response system functioning are thought to be a central mechanism by which exposure to adverse early-life environments influences human development. Although early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis in rodents, evidence from human studies is inconsistent. We present results...

Ecological opportunity and the evolution of canids [Evolution]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
A long-standing hypothesis in adaptive radiation theory is that ecological opportunity constrains rates of phenotypic evolution, generating a burst of morphological disparity early in clade history. Empirical support for the early burst model is rare in comparative data, however. One possible reason for this lack of support is that most...

Comparative dynamics of marine biodiversity [Evolution]

PNAS Early Edition Articles - Mon, 04/20/2015 - 14:03
Paleontological data provide essential insights into the processes shaping the spatial distribution of present-day biodiversity. Here, we combine biogeographic data with the fossil record to investigate the roles of parallelism (similar diversities reached via changes from similar starting points), convergence (similar diversities reached from different starting points), and divergence in...
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