Proceedings of the Natural Academy of Sciences

Syndicate content Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences RSS feed -- current issue
Updated: 43 weeks 3 days ago

Non-Darwinian evolution and high tumor diversity [Evolution]

Tue, 11/24/2015 - 13:04
The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide...
Categories: Journal Articles

PD-1 variants for immunotherapy and PET imaging [Immunology and Inflammation]

Tue, 11/24/2015 - 13:04
Signaling through the immune checkpoint programmed cell death protein-1 (PD-1) enables tumor progression by dampening antitumor immune responses. Therapeutic blockade of the signaling axis between PD-1 and its ligand programmed cell death ligand-1 (PD-L1) with monoclonal antibodies has shown remarkable clinical success in the treatment of cancer. However, antibodies have...
Categories: Journal Articles

Extracatalytic function of CD45 in B cells [Immunology and Inflammation]

Tue, 11/24/2015 - 13:04
The receptor-like tyrosine phosphatase CD45 regulates antigen receptor signaling by dephosphorylating the C-terminal inhibitory tyrosine of the src family kinases. However, despite its abundance, the function of the large, alternatively spliced extracellular domain of CD45 has remained elusive. We used normally spliced CD45 transgenes either incorporating a phosphatase-inactivating point mutation...
Categories: Journal Articles

ImmunoPET imaging of high-grade gliomas [Medical Sciences]

Tue, 11/24/2015 - 13:04
Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme...
Categories: Journal Articles

LSP1 in RA [Medical Sciences]

Tue, 11/24/2015 - 13:04
Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of...
Categories: Journal Articles

Stem cell signature in aggressive prostate cancer [Medical Sciences]

Tue, 11/24/2015 - 13:04
Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells....
Categories: Journal Articles

Activity-dependent FMRP translation by HuR binding [Neuroscience]

Tue, 11/24/2015 - 13:04
Fragile X syndrome is a common cause of intellectual disability and autism spectrum disorder. The gene underlying the disorder, fragile X mental retardation 1 (FMR1), is silenced in most cases by a CGG-repeat expansion mutation in the 5′ untranslated region (UTR). Recently, we identified a variant located in the 3′UTR...
Categories: Journal Articles

Cocaine on gene transcription via sigma-1 receptor [Pharmacology]

Tue, 11/24/2015 - 13:04
The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at...
Categories: Journal Articles

Vacuolar phosphate transporter in plants [Plant Biology]

Tue, 11/24/2015 - 13:04
Inorganic phosphate (Pi) is stored in the vacuole, allowing plants to adapt to variable Pi availability in the soil. The transporters that mediate Pi sequestration into vacuole remain unknown, however. Here we report the functional characterization of Vacuolar Phosphate Transporter 1 (VPT1), an SPX domain protein that transports Pi into...
Categories: Journal Articles

Hepatic diurnal transcription and translation [Systems Biology]

Tue, 11/24/2015 - 13:04
Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously...
Categories: Journal Articles

Correction for O’Dwyer et al., Backbones of evolutionary history test biodiversity theory for microbes [Correction]

Tue, 11/24/2015 - 13:04
ECOLOGY Correction for “Backbones of evolutionary history test biodiversity theory for microbes,” by James P. O’Dwyer, Steven W. Kembel, and Thomas J. Sharpton, which appeared in issue 27, July 7, 2015, of Proc Natl Acad Sci USA (112:8356–8361; first published June 23, 2015; 10.1073/pnas.1419341112). The authors note that, due to...
Categories: Journal Articles

Correction for Rasmussen et al., Purkinȷe cell activity during classical conditioning with different conditional stimulus explains central tenet of Rescorla-Wagner model [Correction]

Tue, 11/24/2015 - 13:04
NEUROSCIENCE, PSYCHOLOGICAL AND COGNITIVE SCIENCES Correction for “Purkinje cell activity during classical conditioning with different conditional stimulus explains central tenet of Rescorla–Wagner model,” by Anders Rasmussen, Riccardo Zucca, Fredrik Johansson, Dan-Anders Jirenhed, and Germund Hesslow, which appeared in issue 45, November 10, 2015, of Proc Natl Acad Sci USA (112:14060–14065;...
Categories: Journal Articles

Actin in alcohol use disorders [Biological Sciences]

Tue, 11/24/2015 - 13:04
Actin is the most common intracellular protein in eukaryotic cells, with estimates for nonmuscle cells generally ranging from 1–5% of cellular protein (1). Until fairly recently, actin was widely regarded as a ubiquitous and rather humdrum molecule. However, accumulating research is increasingly pointing to a crucial role of impaired actin...
Categories: Journal Articles

Distinguishing phases of biomedical research [Biological Sciences]

Tue, 11/24/2015 - 13:04
Bowen and Casadevall (1) offer data suggesting that research inputs have not been associated with comparable increases in health outcomes over the past five decades. However, their analysis treats biomedical research the same, regardless of whether the research focuses on early phases, (i.e., basic discovery) or late phases, (i.e., comparative...
Categories: Journal Articles

More study needed on biomedical research phases [Biological Sciences]

Tue, 11/24/2015 - 13:04
We thank Kevin Fiscella for his comments (1) on our report (2). Biomedical science is generally broken into early phases, consisting of basic research and applied translational research or therapeutic development, and late phases, including comparative effectiveness, implementation, and dissemination research (3). Fiscella describes the importance of late-phase research in...
Categories: Journal Articles

Vaginal microbiota and preterm birth [Biological Sciences]

Tue, 11/24/2015 - 13:04
We read with interest the excellent publication by DiGiulio et al. (1), which offers some fascinating insight into the composition and stability of the vaginal bacterial microbiome during pregnancy. Our initial impression, which we suspect would be shared by most readers, is that the study provides evidence supporting the concept...
Categories: Journal Articles

Microbiota pathways and preterm birth [Biological Sciences]

Tue, 11/24/2015 - 13:04
We thank Keelan and Payne (1) for their interest in our work (2). Their letter emphasizes intrauterine infection as a potential mechanistic link between the vaginal microbiota and preterm birth. Although we share their view of ascending infection as a possible mechanism, we don’t consider it to be the only...
Categories: Journal Articles

Tau confers MT attraction and steric stabilization [Applied Physical Sciences]

Tue, 11/24/2015 - 13:04
Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer’s. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau...
Categories: Journal Articles

Conserved linker promotes phase separation of Nck [Biochemistry]

Tue, 11/24/2015 - 13:04
The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can be controlled through phase separation of lipids, proteins, and nucleic acids. Collective interactions of multivalent molecules mediated by modular binding domains can induce gelation and phase separation in several cytosolic and membrane-associated systems. The adaptor protein Nck...
Categories: Journal Articles

Allosteric activation of N-WASP by Nck [Biochemistry]

Tue, 11/24/2015 - 13:04
Actin filament networks assemble on cellular membranes in response to signals that locally activate neural Wiskott–Aldrich-syndrome protein (N-WASP) and the Arp2/3 complex. An inactive conformation of N-WASP is stabilized by intramolecular contacts between the GTPase binding domain (GBD) and the C helix of the verprolin-homology, connector-helix, acidic motif (VCA) segment....
Categories: Journal Articles