PNAS Early Edition Articles

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Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNF{alpha}-mediated inflammation and apoptosis [Immunology and Inflammation]

Mon, 04/24/2017 - 12:56
Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under...

Explaining negative kin discrimination in a cooperative mammal society [Evolution]

Mon, 04/24/2017 - 12:56
Kin selection theory predicts that, where kin discrimination is possible, animals should typically act more favorably toward closer genetic relatives and direct aggression toward less closely related individuals. Contrary to this prediction, we present data from an 18-y study of wild banded mongooses, Mungos mungo, showing that females that are...

Endocrine network essential for reproductive success in Drosophila melanogaster [Physiology]

Mon, 04/24/2017 - 12:56
Ecdysis-triggering hormone (ETH) was originally discovered and characterized as a molt termination signal in insects through its regulation of the ecdysis sequence. Here we report that ETH persists in adult Drosophila melanogaster, where it functions as an obligatory allatotropin to promote juvenile hormone (JH) production and reproduction. ETH signaling deficits...

The SP100 component of ND10 enhances accumulation of PML and suppresses replication and the assembly of HSV replication compartments [Microbiology]

Mon, 04/24/2017 - 12:56
Nuclear domain 10 (ND10) bodies are small (0.1–1 μM) nuclear structures containing both constant [e.g., promyelocytic leukemia protein (PML), SP100, death domain-associated protein (Daxx)] and variable proteins, depending on the function of the cells or the stress to which they are exposed. In herpes simplex virus (HSV)-infected cells, ND10 bodies...

Biochemical and structural characterization of oxygen-sensitive 2-thiouridine synthesis catalyzed by an iron-sulfur protein TtuA [Biochemistry]

Mon, 04/24/2017 - 12:56
Two-thiouridine (s2U) at position 54 of transfer RNA (tRNA) is a posttranscriptional modification that enables thermophilic bacteria to survive in high-temperature environments. s2U is produced by the combined action of two proteins, 2-thiouridine synthetase TtuA and 2-thiouridine synthesis sulfur carrier protein TtuB, which act as a sulfur (S) transfer enzyme...

BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia [Neuroscience]

Mon, 04/24/2017 - 12:56
Hereditary sensory and autonomic neuropathy type III, or familial dysautonomia [FD; Online Mendelian Inheritance in Man (OMIM) 223900], affects the development and long-term viability of neurons in the peripheral nervous system (PNS) and retina. FD is caused by a point mutation in the gene IKBKAP/ELP1 that results in a tissue-specific...

Melvin M. Grumbach 1925-2016 [Retrospectives]

Mon, 04/24/2017 - 12:56
Generations of clinicians have been faced with often striking developmental and acquired hormonal syndromes associated with reproductive, growth, and metabolic phenotypes. These syndromes have included ambiguous genitalia, anomalies of sexual development, intersex forms, accelerated or delayed puberty, gigantism, and short stature. Although clinical phenotypes of these disorders have been well-established,...

Differences between measured and reported volatile organic compound emissions from oil sands facilities in Alberta, Canada [Environmental Sciences]

Mon, 04/24/2017 - 12:56
Large-scale oil production from oil sands deposits in Alberta, Canada has raised concerns about environmental impacts, such as the magnitude of air pollution emissions. This paper reports compound emission rates (E) for 69–89 nonbiogenic volatile organic compounds (VOCs) for each of four surface mining facilities, determined with a top-down approach...

Structure of a protective epitope of group B Streptococcus type III capsular polysaccharide [Microbiology]

Mon, 04/24/2017 - 12:56
Despite substantial progress in the prevention of group B Streptococcus (GBS) disease with the introduction of intrapartum antibiotic prophylaxis, this pathogen remains a leading cause of neonatal infection. Capsular polysaccharide conjugate vaccines have been tested in phase I/II clinical studies, showing promise for further development. Mapping of epitopes recognized by...

Superconductivity and non-Fermi liquid behavior near a nematic quantum critical point [Physics]

Mon, 04/24/2017 - 12:56
Using determinantal quantum Monte Carlo, we compute the properties of a lattice model with spin 12 itinerant electrons tuned through a quantum phase transition to an Ising nematic phase. The nematic fluctuations induce superconductivity with a broad dome in the superconducting Tc enclosing the nematic quantum critical point. For temperatures...

NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake, translocation, and tolerance in Arabidopsis [Plant Biology]

Mon, 04/24/2017 - 12:56
Members of the aquaporin (AQP) family have been suggested to transport aluminum (Al) in plants; however, the Al form transported by AQPs and the roles of AQPs in Al tolerance remain elusive. Here we report that NIP1;2, a plasma membrane-localized member of the Arabidopsis nodulin 26-like intrinsic protein (NIP) subfamily...

Semibatch monomer addition as a general method to tune and enhance the mechanics of polymer networks via loop-defect control [Chemistry]

Mon, 04/24/2017 - 12:56
Controlling the molecular structure of amorphous cross-linked polymeric materials is a longstanding challenge. Herein, we disclose a general strategy for precise tuning of loop defects in covalent polymer gel networks. This “loop control” is achieved through a simple semibatch monomer addition protocol that can be applied to a broad range...

Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family [Biochemistry]

Mon, 04/24/2017 - 12:56
The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining...

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis [Immunology and Inflammation]

Mon, 04/24/2017 - 12:56
The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type...

Mathematical model of chronic pancreatitis [Medical Sciences]

Mon, 04/24/2017 - 12:56
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, leading to its fibrotic destruction. There are currently no drugs that can stop or slow the progression of the disease. The etiology of the disease is multifactorial, whereas recurrent attacks of acute pancreatitis are thought to precede the development...

Brain networks for confidence weighting and hierarchical inference during probabilistic learning [Psychological and Cognitive Sciences]

Mon, 04/24/2017 - 12:56
Learning is difficult when the world fluctuates randomly and ceaselessly. Classical learning algorithms, such as the delta rule with constant learning rate, are not optimal. Mathematically, the optimal learning rule requires weighting prior knowledge and incoming evidence according to their respective reliabilities. This “confidence weighting” implies the maintenance of an...

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin [Biochemistry]

Mon, 04/24/2017 - 12:56
Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits...

Astrocytes locally translate transcripts in their peripheral processes [Neuroscience]

Mon, 04/24/2017 - 12:56
Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of...

Correction for Naviaux et al., Metabolic features of chronic fatigue syndrome [Corrections]

Mon, 04/24/2017 - 12:56
MEDICAL SCIENCES Correction for “Metabolic features of chronic fatigue syndrome,” by Robert K. Naviaux, Jane C. Naviaux, Kefeng Li, A. Taylor Bright, William A. Alaynick, Lin Wang, Asha Baxter, Neil Nathan, Wayne Anderson, and Eric Gordon, which appeared in issue 37, September 13, 2016, of Proc Natl Acad Sci USA...

Estrogen receptor {beta}, a regulator of androgen receptor signaling in the mouse ventral prostate [Medical Sciences]

Mon, 04/24/2017 - 12:56
As estrogen receptor β−/− (ERβ−/−) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ−/− mice...