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We perform a statistical climatological study of the synoptic- to meso-scale weather conditions favoring significant tornado occurrence to empirically investigate the existence of long term temporal trends. To identify environments that favor tornadoes, we apply an empirical orthogonal function (EOF) analysis to temperature, relative humidity, and winds from the Modern-Era Retrospective analysis for Research and Applications Version 2 (MERRA-2) dataset. We consider MERRA-2 data and tornado data from 1980 to 2017 over four adjacent study regions that span the Central, Midwestern, and Southeastern United States. To identify which EOFs are related to significant tornado occurrence, we fit two separate groups of logistic regression models. The first group (LEOF models) estimates the probability of occurrence of a significant tornado day (EF2-EF5) within each region. The second group (IEOF models) classifies the intensity of tornadic days either as strong (EF3-EF5) or weak (EF1-EF2). When compared to approaches using proxies such as convective available potential energy, our EOF approach is advantageous for two main reasons: first, the EOF approach allows for the discovery of important synoptic- to mesoscale variables previously not considered in the tornado science literature; second, proxy-based analyses may not capture important aspects of three-dimensional atmospheric conditions represented by the EOFs. Indeed, one of our main novel findings is the importance of a stratospheric forcing mode on occurrence of significant tornadoes. Other important novel findings are the existence of long-term temporal trends in the stratospheric forcing mode, in a dry line mode, and in an ageostrophic circulation mode related to the jet stream configuration. A relative risk analysis also indicates that changes in stratospheric forcings are partially or completely offsetting increased tornado risk associated with the dry line mode, except in the eastern Midwest region where tornado risk

Plant growth-promoting bacteria (PGPB) can enhance plant health by facilitating nutrient uptake, nitrogen fixation, protection from pathogens, stress tolerance and/or boosting plant productivity. The genetic determinants that drive the plant–bacteria association remain understudied. To identify genetic loci highly correlated with traits responsive to PGPB, we performed a genome-wide association study (GWAS) using an Arabidopsis thaliana population treated with Azoarcus olearius DQS-4T. Phenotypically, the 305 Arabidopsis accessions tested responded differently to bacterial treatment by improving, inhibiting, or not affecting root system or shoot traits. GWA mapping analysis identified several predicted loci associated with primary root length or root fresh weight. Two statistical analyses were performed to narrow down potential gene candidates followed by haplotype block analysis, resulting in the identification of 11 loci associated with the responsiveness of Arabidopsis root fresh weight to bacterial inoculation. Our results showed considerable variation in the ability of plants to respond to inoculation by A. olearius DQS-4T while revealing considerable complexity regarding statistically associated loci with the growth traits measured. This investigation is a promising starting point for sustainable breeding strategies for future cropping practices that may employ beneficial microbes and/or modifications of the root microbiome.

Background and AimsLimited information exists regarding individual subgroups of recovery from opioid use disorder (OUD) following treatment and how these subgroups may relate to recovery trajectories. We used multi-dimensional criteria to identify OUD recovery subgroups and longitudinal transitions across subgroups. Design, Setting and ParticipantsIn a national longitudinal observational study in the United States, individuals who previously participated in a clinical trial for subcutaneous buprenorphine injections for treatment of OUD were enrolled and followed for an average of 4.2 years after participation in the clinical trial. MeasurementsWe identified recovery subgroups based on psychosocial outcomes including depression, opioid withdrawal and pain. We compared opioid use, treatment utilization and quality of life among these subgroups. FindingsThree dimensions of the recovery process were identified: depression, opioid withdrawal and pain. Using these three dimensions, participants were classified into four recovery subgroups: high-functioning (minimal depression, mild withdrawal and no/mild pain), pain/physical health (minimal depression, mild withdrawal and moderate pain), depression (moderate depression, mild withdrawal and mild/moderate pain) and low-functioning (moderate/severe withdrawal, moderate depression and moderate/severe pain). Significant differences among subgroups were observed for DSM-5 criteria (P < 0.001) and remission status (P < 0.001), as well as with opioid use (P < 0.001), treatment utilization (P < 0.001) and quality of life domains (physical health, psychological, environment and social relationships; Ps < 0.001, Cohen's fs >= 0.62). Recovery subgroup assignments were dynamic, with individuals transitioning across subgroups during the observational period. Moreover, the initial recovery subgroup assignment was minimally predictive of long-term outcomes. ConclusionsThere appear to be four distinct subgroups among individuals in recove

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between self-renewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1’s core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between self-renewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1’s core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.

Background High-throughput sequencing experiments, which can determine allele origins, have been used to assess genome-wide allele-specific expression. Despite the amount of data generated from high-throughput experiments, statistical methods are often too simplistic to understand the complexity of gene expression. Specifically, existing methods do not test allele-specific expression (ASE) of a gene as a whole and variation in ASE within a gene across exons separately and simultaneously. Results We propose a generalized linear mixed model to close these gaps, incorporating variations due to genes, single nucleotide polymorphisms (SNPs), and biological replicates. To improve reliability of statistical inferences, we assign priors on each effect in the model so that information is shared across genes in the entire genome. We utilize Bayesian model selection to test the hypothesis of ASE for each gene and variations across SNPs within a gene. We apply our method to four tissue types in a bovine study to de novo detect ASE genes in the bovine genome, and uncover intriguing predictions of regulatory ASEs across gene exons and across tissue types. We compared our method to competing approaches through simulation studies that mimicked the real datasets. The R package, BLMRM, that implements our proposed algorithm, is publicly available for download at https://github.com/JingXieMIZZOU/BLMRM Conclusions We will show that the proposed method exhibits improved control of the false discovery rate and improved power over existing methods when SNP variation and biological variation are present. Besides, our method also maintains low computational requirements that allows for whole genome analysis.

Bayesian hierarchical models are commonly used for modeling spatially correlated areal data. However, choosing appropriate prior distributions for the parameters in these models is necessary and sometimes challenging. In particular, an intrinsic conditional autoregressive (CAR) hierarchical component is often used to account for spatial association. Vague proper prior distributions have frequently been used for this type of model, but this requires the careful selection of suitable hyperparameters. In this paper, we derive several objective priors for the Gaussian hierarchical model with an intrinsic CAR component and discuss their properties. We show that the independence Jeffreys and Jeffreys-rule priors result in improper posterior distributions, while the reference prior results in a proper posterior distribution. We present results from a simulation study that compares frequentist properties of Bayesian procedures that use several competing priors, including the derived reference prior. We demonstrate that using the reference prior results in favorable coverage, interval length, and mean squared error. Finally, we illustrate our methodology with an application to 2012 housing foreclosure rates in the 88 counties of Ohio.