Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

Annexin A6 is critical to maintain glucose homeostasis and survival during liver regeneration in mice

Background and aims: Liver regeneration requires the organized and sequential activation of events that lead to restoration of hepatic mass. During this process, other vital liver functions need to be preserved, such as maintenance of blood glucose homeostasis, balancing the degradation of hepatic glycogen stores, and gluconeogenesis (GNG). Under metabolic stress, alanine is the main hepatic gluconeogenic substrate, and its availability is the rate-limiting step in this pathway. Na+ -coupled neutral amino acid transporters (SNATs) 2 and 4 are believed to facilitate hepatic alanine uptake. In previous studies, we demonstrated that a member of the Ca2+ -dependent phospholipid binding annexins, Annexin A6 (AnxA6), regulates membrane trafficking along endo- and exocytic pathways. Yet, although AnxA6 is abundantly expressed in the liver, its function in hepatic physiology remains unknown. In this study, we investigated the potential contribution of AnxA6 in liver regeneration. Approach and results: Utilizing AnxA6 knockout mice (AnxA6-/- ), we challenged liver function after partial hepatectomy (PHx), inducing acute proliferative and metabolic stress. Biochemical and immunofluorescent approaches were used to dissect AnxA6-/- mice liver proliferation and energetic metabolism. Most strikingly, AnxA6-/- mice exhibited low survival after PHx. This was associated with an irreversible and progressive drop of blood glucose levels. Whereas exogenous glucose administration or restoration of hepatic AnxA6 expression rescued AnxA6-/- mice survival after PHx, the sustained hypoglycemia in partially hepatectomized AnxA6-/- mice was the consequence of an impaired alanine-dependent GNG in AnxA6-/- hepatocytes. Mechanistically, cytoplasmic SNAT4 failed to recycle to the sinusoidal plasma membrane of AnxA6-/- hepatocytes 48 hours after PHx, impairing alanine uptake and, consequently, glucose production. Conclusions: We conclude that the lack of AnxA6 compromises alanine-dependent GNG and liver regeneration in mice

Effects of a Caffeine-Containing Energy Drink on Simulated Soccer Performance

[Background] To investigate the effects of a caffeine-containing energy drink on soccer performance during a simulated game. A second purpose was to assess the post-exercise urine caffeine concentration derived from the energy drink intake. [Methodology/Principal Findings] Nineteen semiprofessional soccer players ingested 630±52 mL of a commercially available energy drink (sugar-free Red Bull®) to provide 3 mg of caffeine per kg of body mass, or a decaffeinated control drink (0 mg/kg). After sixty minutes they performed a 15-s maximal jump test, a repeated sprint test (7×30 m; 30 s of active recovery) and played a simulated soccer game. Individual running distance and speed during the game were measured using global positioning satellite (GPS) devices. In comparison to the control drink, the ingestion of the energy drink increased mean jump height in the jump test (34.7±4.7 v 35.8±5.5 cm; P<0.05), mean running speed during the sprint test (25.6±2.1 v 26.3±1.8 km · h−1; P<0.05) and total distance covered at a speed higher than 13 km · h−1 during the game (1205±289 v 1436±326 m; P<0.05). In addition, the energy drink increased the number of sprints during the whole game (30±10 v 24±8; P<0.05). Post-exercise urine caffeine concentration was higher after the energy drink than after the control drink (4.1±1.0 v 0.1±0.1 µg · mL−1; P<0.05). [Conclusions/significance] A caffeine-containing energy drink in a dose equivalent to 3 mg/kg increased the ability to repeatedly sprint and the distance covered at high intensity during a simulated soccer game. In addition, the caffeinated energy drink increased jump height which may represent a meaningful improvement for headers or when players are competing for a ball

Development of a Mesoamerican intra-genepool genetic map for quantitative trait loci detection in a drought tolerant × susceptible common bean (Phaseolus vulgaris L.) cross

Drought is a major constraint to common bean (Phaseolus vulgaris L.) production, especially in developing countries where irrigation for the crop is infrequent. The Mesoamerican genepool is the most widely grown subdivision of common beans that include small red, small cream and black seeded varieties. The objective of this study was to develop a reliable genetic map for a Mesoamerican × Mesoamerican drought tolerant × susceptible cross and to use this map to analyze the inheritance of yield traits under drought and fully irrigated conditions over 3 years of experiments. The source of drought tolerance used in the cross was the cream-seeded advanced line BAT477 crossed with the small red variety DOR364 and the population was made up of recombinant inbred lines in the F5 generation. Quantitative trait loci were detected by composite interval mapping for the traits of overall seed yield, yield per day, 100 seed weight, days to flowering and days to maturity for each field environment consisting of two treatments (irrigated and rainfed) and lattice design experiments with three repetitions for a total of six environments. The genetic map based on amplified fragment length polymorphism and random amplified polymorphic DNA markers was anchored with 60 simple sequence repeat (SSR) markers and had a total map length of 1,087.5 cM across 11 linkage groups covering the whole common bean genome with saturation of one marker every 5.9 cM. Gaps for the genetic map existed on linkage groups b03, b09 and b11 but overall there were only nine gaps larger than 15 cM. All traits were inherited quantitatively, with the greatest number for seed weight followed by yield per day, yield per se, days to flowering and days to maturity. The relevance of these results for breeding common beans is discussed in particular in the light of crop improvement for drought tolerance in the Mesoamerican genepool

Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity

Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2Lp compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2Lp mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2Lp/+ enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2Lp/+ embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2Lp/Lp) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos

Human-Computer Interaction and the Future ofWork

Advances in computing technology, changing policies, and slow crises are rapidly changing the way we work. Human-computer interaction (HCI) is a critical aspect of these trends, to understand how workers contend with emerging technologies and how design might support workers and their values and aspirations amidst technological change. This SIG invites HCI researchers across diverse domains to reflect on the range of approaches to future of work research, recognize connections and gaps, and consider how HCI can support workers and their wellbeing in the future

The problematic use of Information and Communication Technologies (ICT) in adolescents by the cross sectional JOITIC study

Background: The emerging field of Information and Communications Technology (ICT) has brought about new interaction styles. Its excessive use may lead to addictive behaviours. The objective is to determine the prevalence of the problematic use of ICT such as Internet, mobile phones and video games, among adolescents enrolled in mandatory Secondary Education (ESO in Spanish) and to examine associated factors. Methods: Cross sectional, multi-centric descriptive study. Population: 5538 students enrolled in years one to four of ESO at 28 schools in the Vallès Occidental region (Barcelona, Spain). Data collection: self-administered socio-demographic and ICT access questionnaire, and validated questionnaires on experiences related to the use of the Internet, mobile phones and video games (CERI, CERM, CERV). Results: Questionnaires were collected from 5,538 adolescents between the ages of 12 and 20 (77.3 % of the total response), 48.6 % were females. Problematic use of the Internet was observed in 13.6 % of the surveyed individuals; problematic use of mobile phones in 2.4 % and problematic use in video games in 6.2 %. Problematic Internet use was associated with female students, tobacco consumption, a background of binge drinking, the use of cannabis or other drugs, poor academic performance, poor family relationships and an intensive use of the computer. Factors associated with the problematic use of mobile phones were the consumption of other drugs and an intensive use of these devices. Frequent problems with video game use have been associated with male students, the consumption of other drugs, poor academic performance, poor family relationships and an intensive use of these games. Conclusions: This study offers information on the prevalence of addictive behaviours of the Internet, mobile phones and video game use. The problematic use of these ICT devices has been related to the consumption of drugs, poor academic performance and poor family relationships. This intensive use may constitute a risk marker for ICT addictio

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

BACKGROUND: Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS: Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS: Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children

Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

<p>Abstract</p> <p>Background</p> <p>Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.</p> <p>Methods</p> <p>6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was ≥ 45%. Cases of influenza like illness (defined as fever (oral temperature ≥37.8°C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.</p> <p>Results</p> <p>TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).</p> <p>Conclusion</p> <p>Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.</p> <p>Trial Registration</p> <p>Clinical trial registery: NCT00197223.</p