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This paper presents a study of the production of a single W boson in association with one or more jets in proton-antiproton collisions at is root s = 1.96 TeV, using the entire data set collected in 2001-2011 by the Collider Detector at Fermilab at the Tevatron, which corresponds to an integrated luminosity of 9.0 fb(-1). The W boson is identified through its leptonic decays into electron and muon. The production cross sections are measured for each leptonic decay mode and combined after testing that the ratio of the W(-> mu v) + jets cross section to the W(-> ev) + jets cross section agrees with the hypothesis of e-mu lepton universality. The combination of measured cross sections, differential in the inclusive jet multiplicity (W + >= N jets with N = 1, 2, 3, or 4) and in the transverse energy of the leading jet, are compared with theoretical predictions.

Preclinical studies implicate insulin signaling as a modulator of dopamine transmission, but human data is currently limited. We hypothesize that changes in the expression of insulin receptor-related genes in the postmortem brain tissue of patients with mood and psychotic disorders mediate the expression of dopamine regulation-related genes. From a database containing microarray data from the post-mortem dorsolateral prefrontal cortex (dlPFC) (healthy controls [HC]: n = 209; patients: n = 321) and hippocampus (HC: n = 180; patients: n = 196), we conducted a hypothesis-driven analysis through the a priori selection of 12 dopamine- and 3 insulin-related genes. Mediation and moderated mediation models, accounting for the role of body mass index (BMI), were used. In the dlPFC, expressions of insulin receptor- and dopamine regulation-related genes were moderated by BMI, with significantly lower expression in high BMI patients. In the hippocampus, there were significantly lower expressions of these genes, which were not moderated by BMI. Illnesses by BMI effects on expression of dopamine genes were fully mediated by expression of insulin receptor gene (INSR). Analysis of conditional indirect effects showed interactions between INSR and BMI, indicating significantly stronger indirect effects at higher BMI values. In the hippocampus we observed that expression of insulin receptor substrate 1 and 2 fully mediated the effects of illnesses on expression of dopamine genes. In conclusion, differential expression of dopamine-related genes was related to altered expression of insulin signaling genes. BMI had region-specific effects, supporting the hypothesis that metabolic systems are critical mediators of dopaminergic function.

We report the molecular, cellular, and clinical features of 5 patients from 3 kindreds with biallelic mutations in the autosomal LIG1 gene encoding DNA ligase 1. The patients exhibited hypogammaglobulinemia, lymphopenia, increased proportions of circulating gamma dT cells, and erythrocyte macrocytosis. Clinical severity ranged from a mild antibody deficiency to a combined immunodeficiency requiring hematopoietic stem cell transplantation. Using engineered LIG1-deficient cell lines, we demonstrated chemical and radiation defects associated with the mutant alleles, which variably impaired the DNA repair pathway. We further showed that these LIG1 mutant alleles are amorphic or hypomorphic, and exhibited variably decreased enzymatic activities, which lead to premature release of unligated adenylated DNA. The variability of the LIG1 genotypes in the patients was consistent with that of their immunological and clinical phenotypes. These data suggest that different forms of autosomal recessive, partial DNA ligase 1 deficiency underlie an immunodeficiency of variable severity.

Here we describe GoFish, a strategy for single-species environmental DNA (eDNA) presence/absence assays using nested PCR. The assays amplify a mitochondrial 12S rDNA segment with vertebrate metabarcoding primers, followed by nested PCR with M13-tailed, species-specific primers. Sanger sequencing confirms positives detected by gel electrophoresis. We first obtained 12S sequences from 77 fish specimens for 36 northwestern Atlantic taxa not well documented in GenBank. Using these and existing 12S records, we designed GoFish assays for 11 bony fish species common in the lower Hudson River estuary and tested seasonal abundance and habitat preference at two sites. Additional assays detected nine cartilaginous fish species and a marine mammal, bottlenose dolphin, in southern New York Bight. GoFish sensitivity was equivalent to Illumina MiSeq metabarcoding. Unlike quantitative PCR (qPCR), GoFish does not require tissues of target and related species for assay development and a basic thermal cycler is sufficient. Unlike Illumina metabarcoding, indexing and batching samples are unnecessary and advanced bioinformatics expertise is not needed. From water collection to Sanger sequencing results, the assay can be carried out in three days. The main limitations to this approach, which employs metabarcoding primers, are the same as for metabarcoding, namely, inability to distinguish species with shared target sequences and inconsistent amplification of rarer eDNA. In addition, the performance of the 20 assays reported here as compared to other single-species eDNA assays is not known. This approach will be a useful addition to current eDNA methods when analyzing presence/absence of known species, when turnaround time is important, and in educational settings.

Assembly of bacterial ring-shaped hexameric replicative helicases on single-stranded (ss) DNA requires specialized loading factors. However, mechanisms implemented by these factors during opening and closing of the helicase, which enable and restrict access to an internal chamber, are not known. Here, we investigate these mechanisms in the Escherichia coli DnaB helicase. bacteriophage lambda helicase loader (lambda P) complex. We show that five copies of lambda P bind at DnaB subunit interfaces and reconfigure the helicase into an open spiral conformation that is intermediate to previously observed closed ring and closed spiral forms; reconfiguration also produces openings large enough to admit ssDNA into the inner chamber. The helicase is also observed in a restrained inactive configuration that poises it to close on activating signal, and transition to the translocation state. Our findings provide insights into helicase opening, delivery to the origin and ssDNA entry, and closing in preparation for translocation.

ADAR1, an RNA-editing enzyme, plays a key role in preventing self-RNAs from triggering autoinflammatory responses. In this issue of EMBO reports, Nakahama and colleagues uncover a novel role for ADAR1 in T cells . The authors report that in T cells, ADAR1-mediated suppression of type I interferon-stimulated gene (ISG) expression is required for thymic T cell self-tolerance and prevention of colitis. These findings establish a novel function of ADAR1 in T cells and suggest that autoreactive T cells may contribute to disease symptoms in autoinflammatory disorders.

Full-length RNA sequencing (RNA-Seq) has been applied to bulk tissue, cell lines and sorted cells to characterize transcriptomes(1)(-11), but applying this technology to single cells has proven to be difficult, with less than ten single-cell transcriptomes having been analyzed thus far(12)(,)(13). Although single splicing events have been described for <= 200 single cells with statistical confidence(14,)(15), full-length mRNA analyses for hundreds of cells have not been reported. Single-cell short-read 3' sequencing enables the identification of cellular subtypes(16)(-21), but full-length mRNA isoforms for these cell types cannot be profiled. We developed a method that starts with bulk tissue and identifies single-cell types and their full-length RNA isoforms without fluorescence-activated cell sorting. Using single-cell isoform RNA-Seq (ScISOr-Seq), we identified RNA isoforms in neurons, astrocytes, microglia, and cell subtypes such as Purkinje and Granule cells, and cell-type-specific combination patterns of distant splice sites(6)(-9.)(22)(,)(23) We used ScISOr-Seq to improve genome annotation in mouse Gencode version 10 by determining the cell-type-specific expression of 18,173 known and 16,872 novel isoforms.

Phenotypic plasticity refers to the capacity of the same organisms to exhibit different characteristics under varied environmental conditions. A plastic developmental program allows organisms to sense environmental cues in early stages of life and express phenotypes that are better fitted to environments encountered later in life. This is often considered an adaptive strategy for living in varying environments as long as the plastic response is sufficiently fast, is accurate, and is not too costly. However, despite direct costs of maintaining plasticity and producing phenotypes, a fundamental constraint on the benefit of phenotypic plasticity comes from the predictability of the future environment based on the environmental cues received during development. Here, we analyze a model of plastic development and derive the limits within which this strategy can promote population growth. An explicit expression for the long-term growth rate of a developmentally plastic population is found, which can be decomposed into several easily interpretable terms, representing the benefits and the limitations of phenotypic plasticity as an adaptation strategy. This growth rate decomposition has a remarkably similar form to the expressions previously obtained for the bet-hedging strategy, in which a population randomly diversifies into coexisting subgroups with different phenotypes, implying that those evolutionary strategies may be unified under a common general framework.