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A critical reanalysis of genomics and well-being [Genetics]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Fredrickson et al. [Fredrickson BL, et al. (2013) Proc Natl Acad Sci USA 110(33):13684–13689] claimed to have observed significant differences in gene expression related to hedonic and eudaimonic dimensions of well-being. Having closely examined both their claims and their data, we draw substantially different conclusions. After identifying some important conceptual...

Paramyxovirus fusion without full 6HB zippering [Microbiology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Enveloped viruses such as HIV and members of the paramyxovirus family use metastable, proteinaceous fusion machineries to merge the viral envelope with cellular membranes for infection. A hallmark of the fusogenic glycoproteins of these pathogens is refolding into a thermodynamically highly stable fusion core structure composed of six antiparallel α-helices,...

MC4Rs in PVH regulate food intake [Neuroscience]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Activation of melanocortin-4 receptors (MC4Rs) restrains feeding and prevents obesity; however, the identity, location, and axonal projections of the neurons bearing MC4Rs that control feeding remain unknown. Reexpression of MC4Rs on single-minded 1 (SIM1)+ neurons in mice otherwise lacking MC4Rs is sufficient to abolish hyperphagia. Thus, MC4Rs on SIM1+ neurons,...

TPC interactome [Cell Biology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
The two-pore channels (TPC1 and TPC2) belong to an ancient family of intracellular ion channels expressed in the endolysosomal system. Little is known about how regulatory inputs converge to modulate TPC activity, and proposed activation mechanisms are controversial. Here, we compiled a proteomic characterization of the human TPC interactome, which...

Prep1 and EMT [Cell Biology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Pre–B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner...

Orientation of objects using magnetic levitation [Applied Physical Sciences]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
This paper describes several noncontact methods of orienting objects in 3D space using Magnetic Levitation (MagLev). The methods use two permanent magnets arranged coaxially with like poles facing and a container containing a paramagnetic liquid in which the objects are suspended. Absent external forcing, objects levitating in the device adopt...

Age and T-cell repertoire [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and...

Taung, metopism, and hominin brain evolution [Anthropology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Falk and colleagues [Falk D, Zollikofer CP, Morimoto N, Ponce de León MS (2012) Proc Natl Acad Sci U S A 109(22):8467–8470] hypothesized that selective pressures favored late persistence of a metopic suture and open anterior fontanelle early in hominin evolution, and they put an emphasis on the Taung Child...

Niche-to-neutral transition in ecology [Physics]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
An ongoing debate in ecology concerns the impacts of ecological drift and selection on community assembly. Here, we show that there is a transition in diverse ecological communities between a selection-dominated regime (the niche phase) and a drift-dominated regime (the neutral phase). Simulations and analytic arguments show that the niche...

Chloride shunt regulation [Cell Biology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
The paracellular pathway through the tight junction provides an important route for transepithelial chloride reabsorption in the kidney, which regulates extracellular salt content and blood pressure. Defects in paracellular chloride reabsorption may in theory cause deregulation of blood pressure. However, there is no evidence to prove this theory or to...

Custos controls {beta}-catenin activity [Developmental Biology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Precise control of the canonical Wnt pathway is crucial in embryogenesis and all stages of life, and dysregulation of this pathway is implicated in many human diseases including cancers and birth defect disorders. A key aspect of canonical Wnt signaling is the cytoplasmic to nuclear translocation of β-catenin, a process...

Design of donecopride, a novel MTDL against AD [Pharmacology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
RS67333 is a partial serotonin subtype 4 receptor (5-HT4R) agonist that has been widely studied for its procognitive effect. More recently, it has been shown that its ability to promote the nonamyloidogenic cleavage of the precursor of the neurotoxic amyloid-β peptide leads to the secretion of the neurotrophic protein sAPPα....

3D cell body shape controls focal adhesions growth [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Cell shape affects proliferation and differentiation, which are processes known to depend on integrin-based focal adhesion (FA) signaling. Because shape results from force balance and FAs are mechanosensitive complexes transmitting tension from the cell structure to its mechanical environment, we investigated the interplay between 3D cell shape, traction forces generated...

H5N1 immunization broadens immunity to influenza [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
The emergence of pandemic influenza viruses poses a major public health threat. Therefore, there is a need for a vaccine that can induce broadly cross-reactive antibodies that protect against seasonal as well as pandemic influenza strains. Human broadly neutralizing antibodies directed against highly conserved epitopes in the stem region of...

CRISPR strategy to cure latent herpes infection [Medical Sciences]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Latent viral infection is a persistent cause of human disease. Although standard antiviral therapies can suppress active viral replication, no existing treatment can effectively eradicate latent infection and therefore a cure is lacking for many prevalent viral diseases. The prokaryotic immune system clustered regularly interspaced short palindromic repeat (CRISPR)/Cas evolved...

RSV attenuation by codon-pair deoptimization [Microbiology]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory-tract disease worldwide. A vaccine or generally effective antiviral drug is not yet available. We designed new live attenuated RSV vaccine candidates by codon-pair deoptimization (CPD). Specifically, viral ORFs were recoded by rearranging existing synonymous codons...

Free energy time course of EMT [Chemistry]

PNAS Early Edition Articles - Mon, 08/25/2014 - 13:38
The epithelial-to-mesenchymal transition (EMT) initiates the invasive and metastatic behavior of many epithelial cancers. Mechanisms underlying EMT are not fully known. Surprisal analysis of mRNA time course data from lung and pancreatic cancer cells stimulated to undergo TGF-β1–induced EMT identifies two phenotypes. Examination of the time course for these phenotypes...
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