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Anti-MERS coronavirus human neutralizing antibody [Microbiology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we...

Variability in red blood cell oxygen affinity [Engineering]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration...

Deep time stability of lizard communities [Evolution]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Whether the structure of ecological communities can exhibit stability over macroevolutionary timescales has long been debated. The similarity of independently evolved Anolis lizard communities on environmentally similar Greater Antillean islands supports the notion that community evolution is deterministic. However, a dearth of Caribbean Anolis fossils—only three have been described to...

PK2 subverts eIF2{alpha} kinases by viral mimicry [Biochemistry]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by eIF2α family kinases is a conserved mechanism to limit protein synthesis under specific stress conditions. The baculovirus-encoded protein PK2 inhibits eIF2α family kinases in vivo, thereby increasing viral fitness. However, the precise mechanism by which PK2 inhibits eIF2α kinase function remains...

Whole-cell catalyst of penicillin G to G-7-ADCA [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Many medically useful semisynthetic cephalosporins are derived from 7-aminodeacetoxycephalosporanic acid (7-ADCA), which has been traditionally made by the polluting chemical method. Here, a whole-cell biocatalytic process based on an engineered Escherichia coli strain expressing 2-oxoglutarate–dependent deacetoxycephalosporin C synthase (DAOCS) for converting penicillin G to G-7-ADCA is developed. The major engineering...

Mitochondrial calcium overload in heart failure [Physiology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for excitation–contraction (E–C) coupling. Mitochondria, the major source of energy, in the form of ATP, required for cardiac contractility, are closely interconnected with the SR, and Ca2+ is essential for optimal function of these organelles. However, Ca2+ accumulation can impair...

Discrete stochastic parametrization [Applied Mathematics]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Many physical systems are described by nonlinear differential equations that are too complicated to solve in full. A natural way to proceed is to divide the variables into those that are of direct interest and those that are not, formulate solvable approximate equations for the variables of greater interest, and...

Fra protein requirement for channels in Anabaena [Microbiology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally, vegetative cells transfer fixed carbon to heterocysts. Several routes have been described for metabolite exchange within the filament, one of which involves communicating channels...

Soil carbon losses by deforestation to tree crops [Environmental Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Tropical deforestation for the establishment of tree cash crop plantations causes significant alterations to soil organic carbon (SOC) dynamics. Despite this recognition, the current Intergovernmental Panel on Climate Change (IPCC) tier 1 method has a SOC change factor of 1 (no SOC loss) for conversion of forests to perennial tree...

Mechanism of {sigma}70-dependent pausing [Biochemistry]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
The movement of RNA polymerase (RNAP) during transcription elongation is modulated by DNA-encoded elements that cause the elongation complex to pause. One of the best-characterized pause sequences is a binding site for the σ70 initiation factor that induces pausing at a site near lambdoid phage late-gene promoters. An essential component...

DNP MAS NMR on channelrhodopsin-2 [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Channelrhodopsin-2 from Chlamydomonas reinhardtii is a light-gated ion channel. Over recent years, this ion channel has attracted considerable interest because of its unparalleled role in optogenetic applications. However, despite considerable efforts, an understanding of how molecular events during the photocycle, including the retinal trans-cis isomerization and the deprotonation/reprotonation of the...

Serologic biomarkers for malaria exposure [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in...

Riverine N2O emissions scale with stream order [Agricultural Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
N2O is an important greenhouse gas and the primary stratospheric ozone depleting substance. Its deleterious effects on the environment have prompted appeals to regulate emissions from agriculture, which represents the primary anthropogenic source in the global N2O budget. Successful implementation of mitigation strategies requires robust bottom-up inventories that are based...

Antipsychotic drug release from dopamine terminals [Pharmacology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it...

Aire, a Brd4 tether [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Aire controls immunologic tolerance by inducing a battery of thymic transcripts encoding proteins characteristic of peripheral tissues. Its unusually broad effect is achieved by releasing RNA polymerase II paused just downstream of transcriptional start sites. We explored Aire’s collaboration with the bromodomain-containing protein, Brd4, uncovering an astonishing correspondence between those...

Brain network reconfiguration for inhibition [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory...

Gating a mechanosensitive channel in cellular flow [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
A multiscale continuum model is constructed for a mechanosensitive (MS) channel gated by tension in a lipid bilayer membrane under stresses due to fluid flows. We illustrate that for typical physiological conditions vesicle hydrodynamics driven by a fluid flow may render the membrane tension sufficiently large to gate a MS...

Social modification of antibiosis in Streptomyces [Microbiology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Despite their importance for humans, there is little consensus on the function of antibiotics in nature for the bacteria that produce them. Classical explanations suggest that bacteria use antibiotics as weapons to kill or inhibit competitors, whereas a recent alternative hypothesis states that antibiotics are signals that coordinate cooperative social...
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