266 research outputs found
Employment-Precipitated Heart Attacks: A Few Legal Issues in Establishing Compensability
I. [Introduction]
II. Compensability … A. In General … B. Usual versus Unusual Exertion in Heart Attack Cases … 1. Legislative Development … 2. Judicial Analogy
III. Rules of Evidence … A. In General … B. Spontaneous Declarations and Res Gestae … C. The “State of Mind” Exception … D. “Habit” … E. The “Dead Man’s Statute” … F. Uniform Business Records as Evidence Ac
Employment-Precipitated Heart Attacks: A Few Legal Issues in Establishing Compensability
I. [Introduction]
II. Compensability … A. In General … B. Usual versus Unusual Exertion in Heart Attack Cases … 1. Legislative Development … 2. Judicial Analogy
III. Rules of Evidence … A. In General … B. Spontaneous Declarations and Res Gestae … C. The “State of Mind” Exception … D. “Habit” … E. The “Dead Man’s Statute” … F. Uniform Business Records as Evidence Ac
Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.
SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans
Observational evidence for self-interacting cold dark matter
Cosmological models with cold dark matter composed of weakly interacting
particles predict overly dense cores in the centers of galaxies and clusters
and an overly large number of halos within the Local Group compared to actual
observations. We propose that the conflict can be resolved if the cold dark
matter particles are self-interacting with a large scattering cross-section but
negligible annihilation or dissipation. In this scenario, astronomical
observations may enable us to study dark matter properties that are
inaccessible in the laboratoryComment: 4 pages, no figures; added references, pedagogical improvements, to
appear in PR
The Lantern Vol. 18, No. 3, Spring 1950
• The Rise and Fall of Mr. Fluff • Thoughts by the Sea • Equality of Men • On Radio Comedians • After Hours • Rain • Morning • Escape from Fear • Book of Red • Poems by a Guy Named Mike • We are the People • Spirit Disrupted • Light • Sonnethttps://digitalcommons.ursinus.edu/lantern/1051/thumbnail.jp
Characterization of the proneural gene regulatory network during mouse telencephalon development
BACKGROUND: The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors. RESULTS: Here we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction. Next, we searched the non-coding sequence surrounding the predicted proneural downstream effector genes for evolutionarily conserved transcription factor binding sites associated with newly defined consensus binding sites for Ngn2 and Mash1. This allowed us to identify potential novel co-factors and co-regulators for proneural proteins, including Creb, Tcf/Lef, Pou-domain containing transcription factors, Sox9, and Mef2a. Finally, a gene regulatory network was delineated using a novel Bayesian-based algorithm that can incorporate information from diverse datasets. CONCLUSION: Together, these data shed light on the molecular pathways regulated by proneural genes and demonstrate that the integration of experimentation with bioinformatics can guide both hypothesis testing and hypothesis generation
Mouse Pancreatic Endocrine Cell Transcriptome Defined in the Embryonic Ngn3-Null Mouse
OBJECTIVE—To document the transcriptome of the pancreatic islet during the early and late development of the mouse pancreas and highlight the qualitative and quantitative features of gene expression that contribute to the specification, growth, and differentiation of the major endocrine cell types. A further objective was to identify endocrine cell biomarkers, targets of diabetic autoimmunity, and regulatory pathways underlying islet responses to physiological and pathological stimuli
PARP1 suppresses homologous recombination events in mice in vivo
Recent studies suggest that PARP1 inhibitors, several of which are currently in clinical trial, may selectively kill BRCA1/2 mutant cancers cells. It is thought that the success of this therapy is based on immitigable lethal DNA damage in the cancer cells resultant from the concurrent loss or inhibition of two DNA damage repair pathways: single-strand break (SSB) repair and homologous recombination repair (HRR). Presumably, inhibition of PARP1 activity obstructs the repair of SSBs and during DNA replication, these lesions cause replication fork collapse and are transformed into substrates for HRR. In fact, several previous studies have indicated a hyper-recombinogenic phenotype in the absence of active PARP1 in vitro or in response to DNA damaging agents. In this study, we demonstrate an increased frequency of spontaneous HRR in vivo in the absence of PARP1 using the pun assay. Furthermore, we found that the HRR events that occur in Parp1 nullizygous mice are associated with a significant increase in large, clonal events, as opposed to the usually more frequent single cell events, suggesting an effect in replicating cells. In conclusion, our data demonstrates that PARP1 inhibits spontaneous HRR events, and supports the model of DNA replication transformation of SSBs into HRR substrates
- …