PNAS Early Edition Articles

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HDAC1 links early life stress to schizophrenia-like phenotypes [Neuroscience]

Mon, 05/22/2017 - 12:50
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA...

Mechanistic insight into the nucleus-vacuole ȷunction based on the Vac8p-Nvȷ1p crystal structure [Biochemistry]

Mon, 05/22/2017 - 12:50
Formation of the nucleus–vacuole junction (NVJ) is mediated by direct interaction between the vacuolar protein Vac8p and the outer nuclear endoplasmic reticulum membrane protein Nvj1p. Herein we report the crystal structure of Vac8p bound to Nvj1p at 2.4-Å resolution. Vac8p comprises a flexibly connected N-terminal H1 helix followed by 12...

Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases [Immunology and Inflammation]

Mon, 05/22/2017 - 12:50
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T...

Retracing Zika’s footsteps across the Americas with computational modeling [Commentaries]

Mon, 05/22/2017 - 12:50
For much of 2016, it was hard to look at the news without seeing a headline about Zika. Images of parents holding newborn children with microcephaly grabbed the world’s attention and spurred the World Health Organization to make a rare declaration of a Public Health Emergency of International Concern (1)....

DNA replication and mismatch repair safeguard against metabolic imbalances [Commentaries]

Mon, 05/22/2017 - 12:50
During DNA replication, the major DNA replicative polymerases Polδ and Polε introduce noncomplementary nucleotides approximately once in every 100,000 polymerization events. Proofreading properties of these polymerases improve their fidelity by 10- to 100-fold, and postreplicative DNA mismatch repair (MMR), which acts as a spell checker to remove mismatches that escape...

The natural productome [Commentaries]

Mon, 05/22/2017 - 12:50
Natural products have inspired many highly impactful human medicines, crop protectants, food preservatives, and biological probes. They also make the world a more wonderful place to see, smell, taste, and feel, by serving as many of the most popular colorants, perfumes, seasonings, and lotions (Fig. 1). Having the capacities to...

Correction for Lucotte et al., Direct visualization of the arterial wall water permeability barrier using CARS microscopy [Corrections]

Mon, 05/22/2017 - 12:50
PHYSIOLOGY, BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for “Direct visualization of the arterial wall water permeability barrier using CARS microscopy,” by Bertrand M. Lucotte, Chloe Powell, Jay R. Knutson, Christian A. Combs, Daniela Malide, Zu-Xi Yu, Mark Knepper, Keval D. Patel, Anna Pielach, Errin Johnson, Lyudmyla Borysova, Kim A. Dora, and...

Bidirectional regulation of A{beta} levels by Presenilin 1 [Neuroscience]

Mon, 05/22/2017 - 12:50
Alzheimer’s disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase...

Inducible CTCF insulator delays the IgH 3' regulatory region-mediated activation of germline promoters and alters class switching [Immunology and Inflammation]

Mon, 05/22/2017 - 12:50
Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3′ regulatory region (3′RR) in...

Extraordinarily rapid speciation in a marine fish [Evolution]

Mon, 05/22/2017 - 12:50
Divergent selection may initiate ecological speciation extremely rapidly. How often and at what pace ecological speciation proceeds to yield strong reproductive isolation is more uncertain. Here, we document a case of extraordinarily rapid speciation associated with ecological selection in the postglacial Baltic Sea. European flounders (Platichthys flesus) in the Baltic...

Confined catalysis under two-dimensional materials [Chemistry]

Mon, 05/22/2017 - 12:50
Confined microenvironments formed in heterogeneous catalysts have recently been recognized as equally important as catalytically active sites. Understanding the fundamentals of confined catalysis has become an important topic in heterogeneous catalysis. Well-defined 2D space between a catalyst surface and a 2D material overlayer provides an ideal microenvironment to explore the...

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer [Medical Sciences]

Mon, 05/22/2017 - 12:50
Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly...

Repression of phosphatidylinositol transfer protein {alpha} ameliorates the pathology of Duchenne muscular dystrophy [Genetics]

Mon, 05/22/2017 - 12:50
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation...

Spatial evolutionary games with weak selection [Applied Mathematics]

Mon, 05/22/2017 - 12:50
Recently, a rigorous mathematical theory has been developed for spatial games with weak selection, i.e., when the payoff differences between strategies are small. The key to the analysis is that when space and time are suitably rescaled, the spatial model converges to the solution of a partial differential equation (PDE)....

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity [Psychological and Cognitive Sciences]

Mon, 05/22/2017 - 12:50
Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference...

Histone-binding of DPF2 mediates its repressive role in myeloid differentiation [Biochemistry]

Mon, 05/22/2017 - 12:50
Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem...

Reassessment of 20th century global mean sea level rise [Sustainability Science]

Mon, 05/22/2017 - 12:50
The rate at which global mean sea level (GMSL) rose during the 20th century is uncertain, with little consensus between various reconstructions that indicate rates of rise ranging from 1.3 to 2 mm⋅y−1. Here we present a 20th-century GMSL reconstruction computed using an area-weighting technique for averaging tide gauge records...

Behavioral and neural correlates to multisensory detection of sick humans [Psychological and Cognitive Sciences]

Mon, 05/22/2017 - 12:50
Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in...

Correction for Dash et al., Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity [Corrections]

Mon, 05/22/2017 - 12:50
MEDICAL SCIENCES Correction for “Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24–mediated toxicity,” by Rupesh Dash, Belal Azab, Bridget A. Quinn, Xuening Shen, Xiang-Yang Wang, Swadesh K. Das, Mohamed Rahmani, Jun Wei, Michael Hedvat, Paul Dent, Igor P. Dmitriev, David T. Curiel, Steven Grant, Bainan Wu,...

Correction for Pivkin et al., Biomechanics of red blood cells in human spleen and consequences for physiology and disease [Corrections]

Mon, 05/22/2017 - 12:50
BIOPHYSICS AND COMPUTATIONAL BIOLOGY, ENGINEERING Correction for “Biomechanics of red blood cells in human spleen and consequences for physiology and disease,” by Igor V. Pivkin, Zhangli Peng, George E. Karniadakis, Pierre A. Buffet, Ming Dao, and Subra Suresh, which appeared in issue 28, July 12, 2016, of Proc Natl Acad...