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U-ISGF3 in HCV infection and interferon response [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Up-regulation of IFN-stimulated genes (ISGs) is sustained in hepatitis C virus (HCV)-infected livers. Here, we investigated the mechanism of prolonged ISG expression and its role in IFN responsiveness during HCV infection in relation to unphosphorylated IFN-stimulated gene factor 3 (U-ISGF3), recently identified as a tripartite transcription factor formed by high...

Decadal acidification in the Atlantic [Environmental Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Global ocean acidification is caused primarily by the ocean’s uptake of CO2 as a consequence of increasing atmospheric CO2 levels. We present observations of the oceanic decrease in pH at the basin scale (50°S–36°N) for the Atlantic Ocean over two decades (1993–2013). Changes in pH associated with the uptake of...

Climate change impacts on childhood undernutrition [Sustainability Science]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Malnutrition is a challenge to the health and productivity of populations and is viewed as one of the five largest adverse health impacts of climate change. Nonetheless, systematic evidence quantifying these impacts is currently limited. Our aim was to assess the scientific evidence base for the impact of climate change...

Treatment for lung SCC with EGFR mutation [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non–small cell lung cancer (NSCLC). However, the clinical...

Warning indicators under different environments [Population Biology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Shifting patterns of temporal fluctuations have been found to signal critical transitions in a variety of systems, from ecological communities to human physiology. However, failure of these early warning signals in some systems calls for a better understanding of their limitations. In particular, little is known about the generality of...

RNA aptamer against p53 single AA mutation [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53...

MIR-derived human insulator sequences [Genetics]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
Insulators are regulatory elements that help to organize eukaryotic chromatin via enhancer-blocking and chromatin barrier activity. Although there are several examples of transposable element (TE)-derived insulators, the contribution of TEs to human insulators has not been systematically explored. Mammalian-wide interspersed repeats (MIRs) are a conserved family of TEs that have...

AAV9 gene therapy delivering MIS in ovarian cancer [Cell Biology]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production...

Cas9 RNP-mediated knock-in human T cells [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 07/27/2015 - 13:04
T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated...

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...
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