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GCTA-GREML accounts for LD [Letters (Online Only)]

PNAS Early Edition Articles - 5 hours 10 min ago
In a recent publication in PNAS, Krishna Kumar et al. (1) claim that “GCTA applied to current SNP data cannot produce reliable or stable estimates of heritability.” We show below that those claims are false due to their misunderstanding of the theory and practice of random-effect models underlying genome-wide complex...

GCTA produces unreliable heritability estimates [Letters (Online Only)]

PNAS Early Edition Articles - 5 hours 19 min ago
In our recent paper in PNAS (1), and subsequently (2), we have analyzed the mathematical model that is stated precisely by Yang et al. (3). As written, their model assumes that (i) the Genetic Relatedness Matrix (GRM) is known exactly, (ii) the phenotypic contributions of each of the P SNPs...

Cold denaturation of the Trp-cage miniprotein [Applied Physical Sciences]

PNAS Early Edition Articles - 5 hours 33 min ago
The functional native states of globular proteins become unstable at low temperatures, resulting in cold unfolding and impairment of normal biological function. Fundamental understanding of this phenomenon is essential to rationalizing the evolution of freeze-tolerant organisms and developing improved strategies for long-term preservation of biological materials. We present fully atomistic...

ProSAAS blocks {alpha}-synuclein neurotoxicity [Neuroscience]

PNAS Early Edition Articles - 5 hours 33 min ago
Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson’s disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named...

Genome-wide map of UV damage formation and repair [Genetics]

PNAS Early Edition Articles - 5 hours 33 min ago
UV-induced DNA lesions are important contributors to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. Genome-wide profiling of repair activity in UV irradiated cells has revealed significant variations in repair kinetics across the genome, not only among large chromatin...

Regulation of animal and cell size by ATX-2 [Biochemistry]

PNAS Early Edition Articles - 5 hours 33 min ago
Dietary restriction (DR) is a metabolic intervention that extends the lifespan of multiple species, including yeast, flies, nematodes, rodents, and, arguably, rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, fecundity, and fat accumulation, as well as slower development. We have identified atx-2, the Caenorhabditis elegans...

Stochastic ice stream dynamics [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - 5 hours 33 min ago
Ice streams are narrow corridors of fast-flowing ice that constitute the arterial drainage network of ice sheets. Therefore, changes in ice stream flow are key to understanding paleoclimate, sea level changes, and rapid disintegration of ice sheets during deglaciation. The dynamics of ice flow are tightly coupled to the climate...

Galanin receptor 1 and depression-like behavior [Neuroscience]

PNAS Early Edition Articles - 5 hours 33 min ago
The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats...

NF-{kappa}B subunits in late B-cell development [Immunology and Inflammation]

PNAS Early Edition Articles - 5 hours 33 min ago
The NF-κB signaling cascade relays external signals essential for B-cell growth and survival. This cascade is frequently hijacked by cancers that arise from the malignant transformation of germinal center (GC) B cells, underscoring the importance of deciphering the function of NF-κB in these cells. The NF-κB signaling cascade is comprised...

Structure of the N-actin complex [Biochemistry]

PNAS Early Edition Articles - 5 hours 33 min ago
Actin polymerizes and forms filamentous structures (F-actin) in the cytoplasm of eukaryotic cells. It also exists in the nucleus and regulates various nucleic acid transactions, particularly through its incorporation into multiple chromatin-remodeling complexes. However, the specific structure of actin and the mechanisms that regulate its polymeric nature inside the nucleus...

Oncogene dosage in t(8;21) leukemia [Medical Sciences]

PNAS Early Edition Articles - 5 hours 33 min ago
Chromosomal translocation 8;21 is found in 40% of the FAB M2 subtype of acute myeloid leukemia (AML). The resultant in-frame fusion protein AML1-ETO (AE) acts as an initiating oncogene for leukemia development. AE immortalizes human CD34+ cord blood cells in long-term culture. We assessed the transforming properties of the alternatively...

Dual role of CO in Pt cluster stability [Chemistry]

PNAS Early Edition Articles - 5 hours 33 min ago
Interactions between catalytically active metal particles and reactant gases depend strongly on the particle size, particularly in the subnanometer regime where the addition of just one atom can induce substantial changes in stability, morphology, and reactivity. Here, time-lapse scanning tunneling microscopy (STM) and density functional theory (DFT)-based calculations are used...

Disappearance of H5 clade 2.3.4.4 in America [Ecology]

PNAS Early Edition Articles - 5 hours 33 min ago
One of the major unresolved questions in influenza A virus (IAV) ecology is exemplified by the apparent disappearance of highly pathogenic (HP) H5N1, H5N2, and H5N8 (H5Nx) viruses containing the Eurasian hemagglutinin 2.3.4.4 clade from wild bird populations in North America. The introduction of Eurasian lineage HP H5 clade 2.3.4.4...

Stress and the mitochondrial GR [Neuroscience]

PNAS Early Edition Articles - 5 hours 33 min ago
Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the...

QnAs with John Rogers [QnAs]

PNAS Early Edition Articles - 5 hours 33 min ago
From soft, stretchable biosensors that move naturally with the human body, to transient, biocompatible electronics that dissolve after use, John Rogers’ inventions seem to have sprung out of science fiction. He has received both a MacArthur Genius Grant and the Lemelson–Massachusetts Institute of Technology Prize for inventors and holds more...

Mechanical signals coordinate embryonic heartbeats [Biophysics and Computational Biology]

PNAS Early Edition Articles - 5 hours 33 min ago
In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions...

Bone-seeking polymeric nanoparticles [Engineering]

PNAS Early Edition Articles - 5 hours 33 min ago
Malignant osteolysis associated with inoperable primary bone tumors and multifocal skeletal metastases remains a challenging clinical problem in cancer patients. Nanomedicine that is able to target and deliver therapeutic agents to diseased bone sites could potentially provide an effective treatment option for different types of skeletal cancers. Here, we report...

Correction for Bastia et al., Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest [Corrections]

PNAS Early Edition Articles - 5 hours 33 min ago
BIOCHEMISTRY Correction for “Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest,” by Deepak Bastia, Pankaj Srivastava, Shamsu Zaman, Malay Choudhury, Bidyut K. Mohanty, Julien Bacal, Lance D. Langston, Philippe Pasero, and Michael E. O’Donnell, which appeared in issue 26, June 28, 2016, of Proc Natl Acad...

Correction for Zou et al., Genetic and socioeconomic study of mate choice in Latinos reveals novel assortment patterns [Corrections]

PNAS Early Edition Articles - 5 hours 33 min ago
GENETICS Correction for “Genetic and socioeconomic study of mate choice in Latinos reveals novel assortment patterns,” by James Y. Zou, Danny S. Park, Esteban G. Burchard, Dara G. Torgerson, Maria Pino-Yanes, Yun S. Song, Sriram Sankararaman, Eran Halperin, and Noah Zaitlen, which appeared in issue 44, November 3, 2015, of...

Variability of marine particle transfer efficiency [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - 5 hours 33 min ago
The “transfer efficiency” of sinking organic particles through the mesopelagic zone and into the deep ocean is a critical determinant of the atmosphere−ocean partition of carbon dioxide (CO2). Our ability to detect large-scale spatial variations in transfer efficiency is limited by the scarcity and uncertainties of particle flux data. Here...
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