266 research outputs found

    Constitutional Law - Sixth Amendment - Defendant\u27s Right of Confrontation - Impeachment to Show Bias

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    The Supreme Court of Pennsylvania held that even if the lower court denies defendants their confrontation right to reveal bias by exposing a witness\u27 pending conviction, the decision will not be reversed if the error was harmless. Commonwealth v. Lane, 621 A.2d 566 (Pa. 1993)

    Reciprocal intronic and exonic histone modification regions in humans.

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    While much attention has been focused on chromatin at promoters and exons, human genes are mostly composed of intronic sequences. Analyzing published surveys of nucleosomes and 41 chromatin marks in humans, we identified histone modifications specifically associated with 5' intronic sequences, distinguishable from promoter marks and bulk nucleosomes. These intronic marks were spatially reciprocal to trimethylated histone H3 Lys36 (H3K36me3), typically transitioning near internal exons. Several marks transitioned near bona fide exons, but not near nucleosomes at exon-like sequences. Therefore, we examined whether splicing affects histone marking. Even with considerable changes in regulated alternative splicing, histone marks were stable. Notably, these findings are consistent with exon definition influencing histone marks. In summary, we show that the location of many intragenic marks in humans can be distilled into a simple organizing principle: association with 5' intronic or 3' exonic regions

    Exportin 1 (Crm1p) Is an Essential Nuclear Export Factor

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    AbstractNuclear protein export is mediated by nuclear export signals (NESs), but the mechanisms governing this transport process are not well understood. Using a novel protein export assay in S. cerevisiae, we identify CRM1 as an essential mediator of nuclear protein export in yeast. Crm1p shows homology to importin β-like transport factors and is able to specifically interact with both the NES motif and the Ran GTPase. A mutation in the shuttling protein Crm1p affects not only protein export, but also mRNA export, indicating that these pathways are tightly coupled in S. cerevisiae. The presented data are consistent with the conclusion that Crm1p is a carrier for the NES-mediated protein export pathway. We propose CRM1 be renamed exportin 1 (XPO1)

    Long-term survival of olfactory sensory neurons after target depletion.

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    Life-long addition and elimination of neurons within the adult olfactory epithelium and olfactory bulb allows for adaptive structural responses to sensory experience, learning, and recovery after injury. The interdependence of the two structures is highlighted by the shortened life span of sensory neurons deprived of bulb contact, and has prompted the hypothesis that trophic cues from the bulb contribute to their survival. The specific identity and source of these signals remain unknown. To investigate the potential role of target neurons in this support, we employed a neurotoxic lesion to selectively remove them while preserving the remaining nerve projection pathway, and examined the dynamics of sensory neuron proliferation and survival. Pulse-labeling of progenitors with bromodeoxyuridine showed that, as with surgical bulb removal, increased apoptosis in the epithelium triggered accelerated production of new neurons after chemical depletion of target cells. Rather than undergoing premature death, a large subpopulation of these neurons survived long term. The combination of increased proliferation and extended survival resulted in essentially normal numbers of new sensory neurons surviving for as long as 5 weeks, with an accompanying restoration of olfactory marker protein expression. Changes in neurotrophic factor expression levels as measured by quantitative polymerase chain reaction (Q-PCR), and in bulb cell populations, including the addition of new neurons generated in the subventricular zone, were observed in the injured bulb. These data indicate that olfactory sensory neurons can adapt to reductions in their normal target field by obtaining sufficient support from remaining or alternative cell sources to survive and maintain their projections

    Stock Composition of Some Sockeye Salmon, Oncorhynchus nerka, Catches in Southeast Alaska, Based on Incidence of Allozyme Variants, Freshwater Ages, and a Brain-Tissue Parasite

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    The incidence of four discrete characters of individual sockeye salmon -two genetically inherited proteins (PGM-1*and PGM-2*), freshwater age at migration, and the presence of the brain-tissue parasite Myxobolus arcticus-in weekly samples from two Alaskan fisheries (Noyes Island in 1986 and Sumner Strait in 1987) were used to infer stock composition of the catches based on corresponding character samples from 73 Alaskan and Canadian stocks. Estimated contributions of 13 stock groups, formed on the basis of character similarity of their members, were roughly consistent with expectations from tagging experiments, knowledge of stock magnitudes, and similar assessments from scales. Imprecision of the estimated contributions by the 13 stock groups limited their practical value; but variability was much reduced for combined estimated contributions by two inclusive categories, namely stock groups whose members had either high or low brainparasite prevalence. Noyes Island catches consisted predominantly of unparasitized fish, most of which were probably of Canadian origin. The majority of Sumner Strait catches consisted of parasitized fish, whose freshwater origins may have been in Alaska or Canada. (PDF file contains 27 pages.

    Associations Between Environmental Conditions and Executive Cognitive Functioning and Behavior During Late Childhood: A Pilot Study

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    Numerous studies have established the influence of detrimental home conditions on child cognition and behavior; however, fewer have assessed these outcomes in the context of relatively “normal” range of home environmental conditions. Given the exquisite sensitivity to the environment of the neural substrates that undergird executive functioning (EF) and behavioral self-regulation in children, it is possible that a range of conditions within the home, even in the absence of maltreatment or economic deprivation, may impact these outcomes. The purpose of the present exploratory investigation was to further define the relationship between features of the home environment using the HOME inventory (a structured interview and observation of parent and child) and several dimensions of child EF and behavioral problems. In addition, this study sought to elucidate potentially differential associations between home and parent-reported neighborhood conditions—a hypothetically less direct influence on cognition in this age group—and level of child functioning. A battery of EF performance tasks and a widely-used checklist of behavioral problems were administered to 66 children, 8–11 years old from a lower middle income, working class sample. Results showed significant relationships between the home environment and several dimensions of EF and behavioral problems. In contrast, neighborhood conferred additional effects only on rule-breaking and aggression, not cognition, which is consistent with evidence that externalizing behavior in this age group becomes increasingly oriented toward outside influences. These findings warrant follow-up studies to establish causality. A broader program of research designed to delve further into the relationship between nuanced influences from the home and child cognition and behavior has implications for parenting strategies that foster healthy development. Neighborhood contexts should also be considered during early and mid-adolescent years based on existing studies and findings reported herein suggesting that this period of newfound autonomy and the heightened significance of peer relationships may influence externalizing behaviors, with implications for protective courses of action

    The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA

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    Numerous RNA binding proteins are deposited onto an mRNA transcript to modulate post-transcriptional processing events ensuring proper mRNA maturation. Defining the interplay between RNA binding proteins that couple mRNA biogenesis events is crucial for understanding how gene expression is regulated. To explore how RNA binding proteins control mRNA processing, we investigated a role for the evolutionarily conserved polyadenosine RNA binding protein, Nab2, in mRNA maturation within the nucleus. This work reveals that nab2 mutant cells accumulate intron-containing pre-mRNA in vivo. We extend this analysis to identify genetic interactions between mutant alleles of nab2 and genes encoding the splicing factor, MUD2, and the RNA exosome, RRP6, with in vivo consequences of altered pre-mRNA splicing and poly(A) tail length control. As further evidence linking Nab2 proteins to splicing, an unbiased proteomic analysis of vertebrate Nab2, ZC3H14, identifies physical interactions with numerous components of the spliceosome. We validated the interaction between ZC3H14 and U2AF2/U2AF^(65). Taking all the findings into consideration, we present a model where Nab2/ZC3H14 interacts with spliceosome components to allow proper coupling of splicing with subsequent mRNA processing steps contributing to a kinetic proofreading step that allows properly processed mRNA to exit the nucleus and escape Rrp6-dependent degradation
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