Striking it Rich by Data Mining

AbstractIn this issue of Cell, Lamb et al. have used a combination of molecular genetics, DNA microarray, and data mining of human tumor expression databases to identify a cdk-independent mechanism by which the interaction of cyclin D1 with the transcription factor C/EBPβ may mediate tumorigenesis

Why do Nigerian manufacturing firms take action on AIDS?

Objective: To identify differences between manufacturing firms in Nigeria that have undertaken HIV/AIDS prevention activities and those that have not as a step toward improving the targeting of HIV policies and interventions. Methods: A survey of a representative sample of registered manufacturing firms in Nigeria, stratified by location, workforce size, and industrial sector. The survey was administered to managers of 232 firms representing most major industrial areas and sectors in March-April 2001. Results: 45.3 percent of the firms’ managers received information about HIV/AIDS from a source outside the firm in 2000; 7.7 percent knew of an employee who was HIV-positive at the time of the survey; and 13.6 percent knew of an employee who had left the firm and/or died in service due to AIDS. Only 31.7 percent of firms took any action to prevent HIV among employees in 2000, and 23.9 percent had discussed the epidemic as a potential business concern. The best correlates of having taken action on HIV were knowledge of an HIV-positive employee or having lost an employee to AIDS (odds ratio [OR] 6.36, 95% confidence interval [CI]: 2.30, 17.57) and receiving information about the disease from an outside source (OR 7.83, 95% CI: 3.46, 17.69). Conclusions: Despite a nationwide HIV seroprevalence of 5.8 percent, as of 2001 most Nigerian manufacturing firm managers did not regard HIV/AIDS as a serious problem and had neither taken any action on it nor discussed it as a business issue. Providing managers with accurate, relevant information about the epidemic and practical prevention interventions might strengthen the business response to AIDS in countries like Nigeria

Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model

Members of the fibroblast growth factor (FGF) family and the FGF receptors (FGFRs) have been implicated in mediating various aspects of mammary gland development and transformation. To elucidate the molecular mechanisms of FGFR1 action in a context that mimics polarized epithelial cells, we have developed an in vitro three-dimensional HC11 mouse mammary epithelial cell culture model expressing a drug-inducible FGFR1 (iFGFR1). Using this conditional model, iFGFR1 activation in these growth-arrested and polarized mammary acini initially led to reinitiation of cell proliferation, increased survival of luminal cells, and loss of cell polarity, resulting in the disruption of acinar structures characterized by the absence of an empty lumen. iFGFR1 activation also resulted in a gain of invasive properties and the induction of matrix metalloproteinase 3 (MMP-3), causing the cleavage of E-cadherin and increased expression of smooth muscle actin and vimentin. The addition of a pan MMP inhibitor abolished these phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or survival

Chk1 Haploinsufficiency Results in Anemia and Defective Erythropoiesis

Erythropoiesis is a highly regulated and well-characterized developmental process responsible for providing the oxygen transport system of the body. However, few of the mechanisms involved in this process have been elucidated. Checkpoint Kinase 1 (Chk1) is best known for its role in the cell cycle and DNA damage pathways, and it has been shown to play a part in several pathways which when disrupted can lead to anemia.Here, we show that haploinsufficiency of Chk1 results in 30% of mice developing anemia within the first year of life. The anemic Chk1+/- mice exhibit distorted spleen and bone marrow architecture, and abnormal erythroid progenitors. Furthermore, Chk1+/- erythroid progenitors exhibit an increase in spontaneous DNA damage foci and improper contractile actin ring formation resulting in aberrant enucleation during erythropoiesis. A decrease in Chk1 RNA has also been observed in patients with refractory anemia with excess blasts, further supporting a role for Chk1 in clinical anemia.Clinical trials of Chk1 inhibitors are currently underway to treat cancer, and thus it will be important to track the effects of these drugs on red blood cell development over an extended period. Our results support a role for Chk1 in maintaining the balance between erythroid progenitors and enucleated erythroid cells during differentiation. We show disruptions in Chk1 levels can lead to anemia

Noncognitive skills in the classroom

This book provides an overview of recent research on the relationship between noncognitive attributes (motivation, self efficacy, resilience) and academic outcomes (such as grades or test scores). We focus primarily on how these sets of attributes are measured and how they relate to important academic outcomes. Noncognitive attributes are those academically and occupationally relevant skills and traits that are not “cognitive”—that is, not specifically intellectual or analytical in nature. We examine seven attributes in depth and critique the measurement approaches used by researchers and talk about how they can be improved.Publishe

Lesions of the Perirhinal Cortex but Not of the Frontal, Medial Prefrontal, Visual, or Insular Cortex Block Fear-Potentiated Startle Using a Visual Conditioned Stimulus

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and l-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory

Comparative Epigenomic Analysis of Murine and Human Adipogenesis

We report the generation and comparative analysis of genome-wide chromatin state maps, PPARγ and CTCF localization maps, and gene expression profiles from murine and human models of adipogenesis. The data provide high-resolution views of chromatin remodeling during cellular differentiation and allow identification of thousands of putative preadipocyte- and adipocyte-specific cis-regulatory elements based on dynamic chromatin signatures. We find that the specific locations of most such elements differ between the two models, including at orthologous loci with similar expression patterns. Based on sequence analysis and reporter assays, we show that these differences are determined, in part, by evolutionary turnover of transcription factor motifs in the genome sequences and that this turnover may be facilitated by the presence of multiple distal regulatory elements at adipogenesis-dependent loci. We also utilize the close relationship between open chromatin marks and transcription factor motifs to identify and validate PLZF and SRF as regulators of adipogenesis.National Institutes of Health (U.S.) (DK63906)American Diabetes Association (Career Development Award)Pennington Biomedical Research FoundationNORC Center (Grant #1P30 DK072476

Behavioral effects of sequential and one-stage ablations of orbital prefrontal cortex in the monkey

The purpose of this investigation was to determine whether sequential (i.e., serial) ablation of the monkey's orbital prefrontal cortex would lead to a reduction in the severity of the behavioral impairment usually associated with one-stage bilateral removal of this tissue. The lateral orbital cortex was ablated in four operations spaced 3 weeks apart or in a one-stage procedure. The monkeys were examined on a visual go-no go differentiation task, spatial delayed-alternation, and object reversal learning. The results reveal no differences between the effects of sequential and one-stage ablations. These findings differ from previous experiments that demonstrated a degree of functional recovery after the sequential removal of a sector of the dorsolateral prefrontal cortex. Since lesion studies with infant monkeys have also demonstrated that functional recovery occurs after early ablation of dorsolateral cortex but not after early removal of orbital frontal cortex, recovery of behavioral functions after infant and sequential lesions may involve similar neural mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33885/1/0000150.pd

Nobody Wants to Be Narcan\u27d: A Pilot Qualitative Analysis of Drug Users\u27 Perspectives on Naloxone

INTRODUCTION: Bystander naloxone distribution is an important component of public health initiatives to decrease opioid-related deaths. While there is evidence supporting naloxone distribution programs, the effects of increasing naloxone availability on the behavior of people who use drugs have not been adequately delineated. In this study we sought to 1) evaluate whether individuals\u27 drug use patterns have changed due to naloxone availability; and 2) explore individuals\u27 knowledge of, access to, experiences with, and perceptions of naloxone. METHODS: We conducted a pilot study of adults presenting to the emergency department whose medical history included non-medical opioid use. Semi-structured interviews were conducted with participants and thematic analysis was used to code and analyze interview transcripts. RESULTS: Ten participants completed the study. All were aware of naloxone by brand name (Narcan) and had been trained in its use, and all but one had either currently or previously possessed a kit. Barriers to naloxone administration included fear of legal repercussions, not having it available, and a desire to avoid interrupting another user\u27s high. Of the eight participants who reported being revived with naloxone at least once during their lifetime, all described experiencing a noxious physical response and expressed a desire to avoid receiving it again. Furthermore, participants did not report increasing their use of opioids when naloxone was available. CONCLUSIONS: Participants were accepting of and knowledgeable about naloxone, and were willing to administer naloxone to save a life. Participants tended to use opioids more cautiously when naloxone was present due to fears of experiencing precipitated withdrawal. This study provides preliminary evidence countering the unsubstantiated narrative that increased naloxone availability begets more high-risk opioid use and further supports increasing naloxone access