Jazzing Up Next-Gen Librarians for Freshman Engineering Instruction Delivery

Because of the need for science and engineering librarians, both nationwide and at West Virginia University (WVU), a model of Introduction to STEM Disciplines’ Information Use and Mentoring occurred at WVU. The engineering librarians introduced new resident librarians and a graduate research assistant to the Freshman Engineering program and involved them in teaching several engineering information literacy sessions. The goal of engaging the new librarians into the educational activities was to motivate their learning, gain feedback on current teaching strategies and fresh ideas for possible future implementation, and facilitate buy-in of the need for and role of STEM-specific librarians. The new team members learned the specific information literacy resources for the engineering field, provided feedback on the teaching methods, offered new ideas for implementation, and engaged with the engineering faculty and current STEM librarians about possible modifications to the types of information offered and the timing of its delivery

Role of dopamine in dorsal medial prefrontal cortex in yohimbine-induced reinstatement of food seeking in rats

In humans, relapse to maladaptive eating habits during dieting is often provoked by stress.Weadapted a drug relapse-reinstatement model to study the role of stress in relapse to food seeking (Nair et al., Prog. Neurobiol., 2009). In our model, the anxiogenic drug yohimbine, an alpha-2 adrenoceptor antagonist, that causes stress-like responses in humans and laboratory animals, reliably reinstates food seeking.Werecently found that yohimbine-induced reinstatement of food seeking is attenuated by systemic injections of SCH23390 (a D1-family receptor antagonist) but not clonidine (an alpha-2 adrenoceptor agonist). Here, we studied the role of the medial prefrontal cortex (mPFC) in yohimbine-induced reinstatement. We trained food-restricted rats to lever-press for 35% high-fat pellets every other day (9–15 3 h sessions). We then extinguished the food-reinforced operant responding for 10–14 days by removing the pellets. Subsequently, we tested the effect of systemic injections of yohimbine (0, 2 mg/kg) on reinstatement of food seeking. In Exp. 1we found that yohimbine-induced reinstatement was associated with strong induction of Fos (a marker of neuronal activity) in the dorsal mPFC and weaker Fos induction in the ventral mPFC. In Exp. 2 we found that dorsal but not ventral mPFC injections of the D1-family receptor antagonist SCH23390 (0.5, 1.0g/side) decreased yohimbine-induced reinstatement of food seeking. Our data indicate a critical role of dorsal mPFC dopamine in reinstatement food seeking induced by the pharmacological stressor yohimbine

Psychomotor stimulant self administration as a function of dosage per injection in the Rhesus monkey

The relationships between drug dosage per injection and response rate, and drug dosage per injection and total daily drug intake were ascertained in Rhesus monkeys which self-administered cocaine, pipradrol, methylphenidate and phenmetrazine intravenously. The study demonstrated the monkeys would self-administer all of these compounds over a wide range of dosages. Furthermore, the magnitude of reinforcement, i.e., dosage per injection, and the rate of responding in self-administering these compounds were inversely related. However, total daily drug intake was independent of the dosage per injection over a wide range of dosages. The results indicate that either the subjects can compensate for large changes in unit dosage so that daily drug intake remains stable or that a direct effect of these compounds functions in limiting their self-administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46379/1/213_2004_Article_BF00401789.pd

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

HST/WFPC2 and VLA Observations of the Ionized Gas in the Dwarf Starburst Galaxy NGC 4214

We present new H alpha and [O III] 5007 narrow band images of the starbursting dwarf galaxy NGC 4214, obtained with the WFPC2 onboard HST, together with VLA observations of the same galaxy. The HST images resolve features down to physical scales of 2-5 pc, revealing several young (<10 Myr) star forming complexes of various ionized gas morphologies (compact knots, complete or fragmentary shells) and sizes (10-200 pc). Our results are consistent with a uniform set of evolutionary trends: The youngest, smaller, filled regions that presumably are those just emerging from dense star forming clouds, tend to be of high excitation and are highly obscured. Evolved, larger shell-like regions have lower excitation and are less extincted due of the action of stellar winds and supernovae. In at least one case we find evidence for induced star formation which has led to a two-stage starburst. Age estimates based on W(H alpha) measurements do not agree with those inferred from wind-driven shell models of expanding H II regions. The most likely explanation for this effect is the existence of a 2 Myr delay in the formation of superbubbles caused by the pressure exerted by the high density medium in which massive stars are born. We report the detection of a supernova remnant embedded in one of the two large H II complexes of NGC 4214. The dust in NGC 4214 is not located in a foreground screen but is physically associated with the warm ionized gas.Comment: 41 pages, including 9 figures and 7 tables. To appear in the November issue of the Astronomical Journa

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts