Amygdaloid involvement in the defensive behavior of mice exposed to the open elevated plus-maze

Previous studies have shown that the exposure to an open elevated plus maze (oEPM, an EPM with all four open arms) elicits fear/anxiety-related responses in laboratory rodents. However, very little is known about the underlying neural substrates of these defensive behaviors. Accordingly, the present study investigated the effects of chemical inactivation of the amygdala [through local injection of cobalt chloride (CoCl2: a nonspecific synaptic blocker)] on the behavior of oEPM-exposed mice. In a second experiment, the pattern of activation of the basolateral (BLA) and central (CeA) nuclei of the amygdala was assessed through quantification of Fos protein expression in mice subjected to one of several behavioral manipulations. To avoid the confound of acute handling stress, 4 independent groups of mice were habituated daily for 10 days to an enclosed EPM (eEPM) and, on day 11 prior to immunohistochemistry, were either taken directly from their home cage (control) or individually exposed for 10 min to a new clean holding cage (novelty), an eEPM, or the oEPM. An additional group of mice (maze-naïve) was not subjected to either the habituation or exposure phase but were simply chosen at random from their home cages to undergo an identical immunohistochemistry procedure. Results showed that amygdala inactivation produced an anxiolytic-like profile comprising reductions in time spent in the proximal portions of the open arms and total stretched attend postures (SAP) as well as increases in time spent in the distal portions of the open arms and total head-dipping. Moreover, Fos-positive labeled cells were bilaterally increased in the amygdaloid complex, particularly in the BLA, of oEPM-exposed animals compared to all other groups. These results suggest that the amygdala (in particular, its BLA nucleus) plays a key role in the modulation of defensive behaviors in oEPM-exposed mice

Survival trends for small intestinal cancer in England and Wales, 1971–1990: national population-based study

This population-based study examines prognostic factors and survival trends among adults (15–99 years) diagnosed with small intestinal cancer in England and Wales during 1971–1990 and followed up to 1995. During this period, the 1- and 5-year age-standardised relative survival rates for small intestinal cancers combined were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients with advanced age and the most deprived patients had the poorest prognosis. For all small bowel tumours combined, the excess risk of death fell significantly by 6–9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR) 0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR fell by about 14% (95% CI 5–22%) every 4 years between 1979 and 1990, and a similar trend for jejunal tumours was of borderline significance. Further population-based investigations linking survival data to individual data on diagnostic methods and types of treatment are needed

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks

Determinants of linear growth from infancy to school-aged years: a population-based follow-up study in urban Amazonian children

Background: Although linear growth during childhood may be affected by early-life exposures, few studies have examined whether the effects of these exposures linger on during school age, particularly in low-and middle-income countries. Methods: We conducted a population-based longitudinal study of 256 children living in the Brazilian Amazon, aged 0.1 y to 5.5 y in 2003. Data regarding socioeconomic and maternal characteristics, infant feeding practices, morbidities, and birth weight and length were collected at baseline of the study (2003). Child body length/height was measured at baseline and at follow-up visits (in 2007 and 2009). Restricted cubic splines were used to construct average height-for-age Z score (HAZ) growth curves, yielding estimated HAZ differences among exposure categories at ages 0.5 y, 1 y, 2 y, 5 y, 7 y, and 10 y. Results: At baseline, median age was 2.6 y (interquartile range, 1.4 y-3.8 y), and mean HAZ was -0.53 (standard deviation, 1.15); 10.2% of children were stunted. In multivariable analysis, children in households above the household wealth index median were 0.30 Z taller at age 5 y (P = 0.017), and children whose families owned land were 0.34 Z taller by age 10 y (P = 0.023), when compared with poorer children. Mothers in the highest tertile for height had children whose HAZ were significantly higher compared with those of children from mothers in the lowest height tertile at all ages. Birth weight and length were positively related to linear growth throughout childhood; by age 10 y, children weighing >3500 g at birth were 0.31 Z taller than those weighing 2501 g to 3500 g (P = 0.022) at birth, and children measuring >= 51 cm at birth were 0.51 Z taller than those measuring <= 48 cm (P = 0.005). Conclusions: Results suggest socioeconomic background is a potentially modifiable predictor of linear growth during the school-aged years. Maternal height and child's anthropometric characteristics at birth are positively associated with HAZ up until child age 10 y.Brazilian National Counsel of Technological and Scientific DevelopmentBrazilian National Counsel of Technological and Scientific DevelopmentCNPq [551359/2001-3, 502937/2003-3, 307728/2006-4, 470573/2007-4]CNPqSao Paulo Research FoundationSao Paulo Research FoundationFAPESP [2007/53042-1, 2008/57796-3]FAPESPOrganization of American StatesOrganization of American States [20100656

Longer First Introns Are a General Property of Eukaryotic Gene Structure

While many properties of eukaryotic gene structure are well characterized, differences in the form and function of introns that occur at different positions within a transcript are less well understood. In particular, the dynamics of intron length variation with respect to intron position has received relatively little attention. This study analyzes all available data on intron lengths in GenBank and finds a significant trend of increased length in first introns throughout a wide range of species. This trend was found to be even stronger when using high-confidence gene annotation data for three model organisms (Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster) which show that the first intron in the 5′ UTR is - on average - significantly longer than all downstream introns within a gene. A partial explanation for increased first intron length in A. thaliana is suggested by the increased frequency of certain motifs that are present in first introns. The phenomenon of longer first introns can potentially be used to improve gene prediction software and also to detect errors in existing gene annotations

HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention

Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy

Internationalisation speed and MNE performance: A study of the market-seeking expansion of retail MNEs

Existing research is divided on whether firms that rapidly expand their overseas operations perform better than firms that internationalize slowly. Drawing on Penrose’s theory of the growth of the firm we argue that the positive effects of rapid internationalization give way to negative effects with increasing internationalization speed, leading to an inverted U-shaped association between internationalization speed and firm performance. We analyse the market-seeking expansion of 110 retailers over a 10-year period (2003–2012) and find support for a curvilinear relationship between internationalization speed and firm performance that is moderated by the geographic scope of firms’ internationalization path and firms’ international experience. Our study contributes to resolving conflicting views on the link between internationalization speed and firm performance

The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response

The mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping and distinct sets of mRNA targets, including highly translated mRNAs such as those encoding ribosomal proteins. In paralell, transcriptome analysis of slf1Δ and sro9Δ mutant strains indicated altered gene expression in similar functional classes of mRNAs following loss of each factor. The loss of SLF1 had a greater impact on the transcriptome, and in particular, revealed changes in genes involved in the oxidative stress response. slf1Δ cells are more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells enriched Slf1p targets encoding antioxidants and other proteins required for oxidant tolerance. To quantify these effects at the protein level, we used label-free mass spectrometry to compare the proteomes of wild-type and slf1Δ strains following oxidative stress. This analysis identified several proteins which are normally induced in response to hydrogen peroxide, but where this increase is attenuated in the slf1Δ mutant. Importantly, a significant number of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets. We show that Slf1p remains associated with the few translating ribosomes following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes and members of the eIF4E/eIF4G/Pab1p ‘closed loop’ complex suggesting that Slf1p interacts with actively translated mRNAs following stress. Finally, mutational analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p, independent of its RNA binding La-motif. Together, our results indicate that Slf1p mediates a translational response to oxidative stress via mRNA-specific translational control