Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Melanin concentrating hormone (MCH) is a regulator of ingestive behavior, but several issues regarding its effects on specific components of ingestive behavior remain to be elucidated. Therefore, we injected, in the 3rd ventricle of male Wistar rats, saline, MCH (5 mu g), MCH (5 mu g) together with a MCH1-R antagonist (A, 10 mu g) and the antagonist alone (A, 10 mu g). Our results show that (1) central administration of MCH stimulates food intake (lab chow and medium high fat diet) and this can be blocked by a MCH1-R antagonist; (2) the MCH-induced increase in food intake is mediated through increased meal number, meal duration and meal size; (3) the MCH1-R antagonist is able to significantly reduce the intake of a highly palatable food (condensed sweet milk) and is more effective in blocking MCH-induced food intake when rats are fed a palatable medium high fat food; and (4) MCH stimulated water intake independently from and disproportionately to food intake. In conclusion, our results point to an involvement of endogenous MCH in the enhanced intake of palatable food. Furthermore, they confirm that MCH stimulates not only food intake but also water intake. (c) 2005 Elsevier B.V. All rights reserved

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Measuring the effectiveness of in-hospital and on-base Prevent Alcohol and Risk-related Trauma in Youth (P.A.R.T.Y.) programs on reducing alcohol related harms in naval trainees: P.A.R.T.Y. Defence study protocol

Abstract Background Reducing alcohol related harms in Australian Defence Force (ADF) trainees has been identified as a priority, but there are few evidence-based prevention programs available for the military setting. The study aims to test whether the P.A.R.T.Y. program delivered in-hospital or on-base, can reduce harmful alcohol consumption among ADF trainees. Methods/design The study is a 3-arm randomized controlled trial, involving 953 Royal Australian Navy trainees from a single base. Trainees, aged 18 to 30 years, will be randomly assigned to the study arms: i. in-hospital P.A.R.T.Y.; ii. On-base P.A.R.T.Y.; and iii. Control group. All groups will receive the routine ADF annual alcohol awareness training. The primary outcome is the proportion of participants reporting an Alcohol Use Disorders Identification Test (AUDIT) score of 8 or above at 12 months’ post-intervention. The secondary outcome is the number of alcohol related incidents reported to the Royal Australian Navy (RAN) in the 12 months’ post-intervention. Discussion This is the first trial of the use of the P.A.R.T.Y. program in the military. If the proposed intervention proves efficacious, it may be a useful program in the early education of RAN trainees. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001332617 , date of registration: 18/12/2014 ‘retrospectively registered’

What is the role of the film viewer? The effects of narrative comprehension and viewing task on gaze control in film

Film is ubiquitous, but the processes that guide viewers' attention while viewing film narratives are poorly understood. In fact, many film theorists and practitioners disagree on whether the film stimulus (bottom-up) or the viewer (top-down) is more important in determining how we watch movies. Reading research has shown a strong connection between eye movements and comprehension, and scene perception studies have shown strong effects of viewing tasks on eye movements, but such idiosyncratic top-down control of gaze in film would be anathema to the universal control mainstream filmmakers typically aim for. Thus, in two experiments we tested whether the eye movements and comprehension relationship similarly held in a classic film example, the famous opening scene of Orson Welles' Touch of Evil (Welles & Zugsmith, Touch of Evil, 1958). Comprehension differences were compared with more volitionally controlled task-based effects on eye movements. To investigate the effects of comprehension on eye movements during film viewing, we manipulated viewers' comprehension by starting participants at different points in a film, and then tracked their eyes. Overall, the manipulation created large differences in comprehension, but only produced modest differences in eye movements. To amplify top-down effects on eye movements, a task manipulation was designed to prioritize peripheral scene features: a map task. This task manipulation created large differences in eye movements when compared to participants freely viewing the clip for comprehension. Thus, to allow for strong, volitional top-down control of eye movements in film, task manipulations need to make features that are important to narrative comprehension irrelevant to the viewing task. The evidence provided by this experimental case study suggests that filmmakers' belief in their ability to create systematic gaze behavior across viewers is confirmed, but that this does not indicate universally similar comprehension of the film narrative

Paving the way for research findings: writers' rhetorical choices in education and applied linguistics

Notwithstanding the existence of previous investigations into how research results are presented in different academic disciplines, fewer studies have looked into how authors pave the way for their results, the interdisciplinary differences in ‘result pavements’, and the interconnections between their communicative functions and linguistic choices. Using the techniques of genre analysis, I have analyzed two corpora of research reports in applied linguistics and education in order to identify the possible ways in which experienced writers schematically pave the way for their findings. Using evidence based on authentic research articles, this study demonstrates how writers set the stage for their research results by (i) demonstrating their control of the structure and flow of result-related information, (ii) connecting past research with a current finding while furnishing pertinent background elements that lead the readership progressively to specific findings, (iii) regenerating readers’ interest in their initial research purposes, and (iv) deploying locatives to embed results in a ‘space-saving strategy’ aimed at presenting an abridged Results section. I have also analyzed interdisciplinary differences in the frequencies of these rhetorical steps and the range of intricate linguistic mechanisms employed by authors as communicative resources in each step to establish a smooth rhetorical transition that sets the stage for their research results

Considering adaptation and the ‘function’ of traits in the classroom, using wiki tools

The conceptual understanding of the process of adaptation (whereby a population becomes better suited to its environment over evolutionary time) is acknowledged to be a difficult one. Many studies have shown that there is an inherent misunderstanding of the term, which is often related to the learner adopting the common rather than biological usage of the term in the learner’s language. But understanding adaptation is essential to understanding evolution, and learners need to be encouraged to understand how to relate hypotheses of the “function” of a trait shown by an individual with the environment in which the individual lives. Here, I describe a practical which encourages a class of learners to create their own organisms, through a series of steps by which they create functional explanations of morphology and behavior. Using a branching process whereby groups of students are split into smaller and smaller subgroups, an artificial phylogeny is created. A wiki system is then used to emphasize how individual species and groups of species are related. The relationship of this practical to problems of tree-thinking is discussed.The conceptual understanding of the process of adaptation (whereby a population becomes better suited to its environment over evolutionary time) is acknowledged to be a difficult one. Many studies have shown that there is an inherent misunderstanding of the term, which is often related to the learner adopting the common rather than biological usage of the term in the learner’s language. However, understanding adaptation is essential to understanding evolution, and learners need to be encouraged to understand how to relate hypotheses of the ‘function’ of a trait shown by an individual with the environment in which the individual lives. Here, I describe a practical which encourages a class of learners to create their own organisms, through a series of steps by which they create functional explanations of morphology and behaviour. Using a branching process whereby groups of students are split into smaller and smaller subgroups, an artificial phylogeny is created. A wiki system is then used to emphasise how individual species and groups of species are related. The relationship of this practical to problems of tree-thinking is discussed

Does Doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer?

Background: In recent years, apart from antibacterial properties, doxycycline is reported to have cytotoxic and anti-proliferative actions in various cancers including colorectal cancer. Colorectal cancer constitutes one of the most common cancers in the western population. Apart from surgery, chemotherapy plays crucial role in the treatment of colorectal cancer. Cisplatin and oxaliplatin are most commonly used platinum compounds for the cancer chemotherapy. This study has looked for any impact of doxycycline on the cytotoxic effects of platinum compounds in colorectal cancer including its mechanisms of actions.Methods: HT 29 colorectal cancer cells were used for this study. These cells were treated with cisplatin and oxaliplatin with or without doxycycline treatment. The caspase 3 gene expression was quantitated by gel electrophoresis and qualitated by real time polymerase chain reactions. The caspase 3 activity was assessed in HT 29 cells with fluorescence kit.Results: The results revealed increased caspase 3 gene expressions and activities in HT 29 cells treated with cisplatin, oxaliplatin and doxycycline; however the combination of doxycycline with cisplatin and oxaliplatin did not report increased caspase 3 gene expressions and activity compared to cisplatin and oxaliplatin alone.Conclusion: We concluded that doxycycline has role in apoptosis induction in the colorectal cancer. However, it did not show any synergy with platinum compounds in the colorectal cancer cells. This study also pointed towards possible caspase-independent actions of doxycycline with cisplatin and oxaliplatin. However, further work is required to underpin the mechanisms of actions of doxycycline