The Mammals of eastern Ethiopia

Zoologica Africana 1(1): 177-17

Astrovirus MLB1 Is Not Associated with Diarrhea in a Cohort of Indian Children

Astroviruses are a known cause of human diarrhea. Recently the highly divergent astrovirus MLB1 (MLB1) was identified in a stool sample from a patient with diarrhea. It has subsequently been detected in stool from individuals with and without diarrhea. To determine whether MLB1 is associated with diarrhea, we conducted a case control study of MLB1. In parallel, the prevalence of the classic human astroviruses (HAstVs) was also determined in the same case control cohort. 400 cases and 400 paired controls from a longitudinal birth cohort in Vellore, India were analyzed by RT-PCR. While HAstVs were associated with diarrhea (p = 0.029) in this cohort, MLB1 was not; 14 of the controls and 4 cases were positive for MLB1. Furthermore, MLB1 viral load did not differ significantly between the cases and controls. The role of MLB1 in human health still remains unknown and future studies are needed

The interplay of intrinsic and extrinsic bounded noises in genetic networks

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a genetic network. The influence of intrinsic and extrinsic noises on genetic networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: $(i)$ the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, $(ii)$ a model of enzymatic futile cycle and $(iii)$ a genetic toggle switch. In $(ii)$ and $(iii)$ we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possibile functional role of bounded noises

Low Self-Esteem and Impairments in Emotion Recognition Predict Behavioural Problems in Children

Research indicates that low self-esteem and impaired emotion recognition are risk factors for antisocial behaviour (ASB). Self-esteem and emotion recognition are essential for successful social interaction and previous research suggests that self-esteem and emotional intelligence are positively related. However, to our knowledge the relationship between these two risk factors for ASB has not been explored in children with behavioural problems. Thus, this study investigated self-esteem and emotion recognition, their relationship with one another and with behavioural problem severity. Participants were 8–11 year olds with behavioural problems (BP; n = 78) who were taking part in an early intervention program, and typically developing controls (TD; n = 54). Participants completed a self-esteem questionnaire and a computerised emotion recognition task. Teachers and parents rated children’s emotional and behavioural problems. BP participants had significantly lower self-esteem and exhibited an impairment in emotion recognition. Self-esteem and emotion recognition were positively related and inversely associated with behavioural problem severity and they predicted behaviour problems independently of one another. This is the first study to show that self-esteem and emotion recognition are related processes in children with behavioural problems and that both predict behavioural problems. This has important implications for the development of intervention strategies

Threshold-dominated regulation hides genetic variation in gene expression networks

<p>Abstract</p> <p>Background</p> <p>In dynamical models with feedback and sigmoidal response functions, some or all variables have thresholds around which they regulate themselves or other variables. A mathematical analysis has shown that when the dose-response functions approach binary or on/off responses, any variable with an equilibrium value close to one of its thresholds is very robust to parameter perturbations of a homeostatic state. We denote this threshold robustness. To check the empirical relevance of this phenomenon with response function steepnesses ranging from a near on/off response down to Michaelis-Menten conditions, we have performed a simulation study to investigate the degree of threshold robustness in models for a three-gene system with one downstream gene, using several logical input gates, but excluding models with positive feedback to avoid multistationarity. Varying parameter values representing functional genetic variation, we have analysed the coefficient of variation (<it>CV</it>) of the gene product concentrations in the stable state for the regulating genes in absolute terms and compared to the <it>CV </it>for the unregulating downstream gene. The sigmoidal or binary dose-response functions in these models can be considered as phenomenological models of the aggregated effects on protein or mRNA expression rates of all cellular reactions involved in gene expression.</p> <p>Results</p> <p>For all the models, threshold robustness increases with increasing response steepness. The <it>CV</it>s of the regulating genes are significantly smaller than for the unregulating gene, in particular for steep responses. The effect becomes less prominent as steepnesses approach Michaelis-Menten conditions. If the parameter perturbation shifts the equilibrium value too far away from threshold, the gene product is no longer an effective regulator and robustness is lost. Threshold robustness arises when a variable is an active regulator around its threshold, and this function is maintained by the feedback loop that the regulator necessarily takes part in and also is regulated by. In the present study all feedback loops are negative, and our results suggest that threshold robustness is maintained by negative feedback which necessarily exists in the homeostatic state.</p> <p>Conclusion</p> <p>Threshold robustness of a variable can be seen as its ability to maintain an active regulation around its threshold in a homeostatic state despite external perturbations. The feedback loop that the system necessarily possesses in this state, ensures that the robust variable is itself regulated and kept close to its threshold. Our results suggest that threshold regulation is a generic phenomenon in feedback-regulated networks with sigmoidal response functions, at least when there is no positive feedback. Threshold robustness in gene regulatory networks illustrates that hidden genetic variation can be explained by systemic properties of the genotype-phenotype map.</p

Molecular characterization of partial-open reading frames 1a and 2 of the human astroviruses in South Korea

Human astroviruses (HAstVs) are among the major causes of gastroenteritis in South Korea. In this study, the partial regions of the open reading frame (ORF) 1a and ORF2 genes of HAstVs from gastroenteritis patients in nine hospitals were sequenced, and the molecular characterization of the viruses was revealed. 89 partial nucleotide sequences of ORF1a and 88 partial nucleotide sequences of ORF2 were amplified from 120 stool specimens. Phylogenetic analysis showed that most of the nucleotide sequences of ORF1a and ORF2 were grouped with HAstV type 1 but had evolutionary genetic distance compared with the reference sequences, such as the HAstV-1 prototype, Dresden strain, and Oxford strain. According to the phylogenetic analysis, some nucleotide sequences including SE0506041, SE0506043, and SE0506058, showed the discrepancy of the genotypes, but there was no proof of recombination among the HAstV types. In conclusion, this study showed that the dominant HAstV isolated from the Seoul metropolitan area in 2004-2005 was HAstV type 1, and that Korean HAstV-1 had the genetic distance in evolution compared with the reference sequences of HAstVs. Lots of nucleotide sequences of the ORF1a and ORF2 genes of HAstV will be useful for studying for the control and prevention of HAstV gastroenteritis in South Korea

CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients

BACKGROUND: CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. METHODS: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. RESULTS: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11-5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53-51.1). CONCLUSION: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients

Second-line treatment for primary central nervous system lymphoma

Failure after first-line treatment was reported in 35–60% of immunocompetent patients with primary central nervous system lymphoma (PCNSL). There are currently no reports focusing on salvage therapy. This review analyses prognostic factors and the efficacy of salvage therapy by focusing on data from papers reporting results of first-line treatment in 355 cases. The study group consisted of 173 patients presenting treatment failure. The interval between failure and death (TTD) was compared for age at relapse (≤60 vs >60 years), type of failure (relapse vs progression), time to relapse (≤12 vs >12 months) and salvage treatment (yes vs no). Median TTD was similar in younger and older patients (P = 0.09). Relapsed patients had a longer TTD than patients with progressive disease (P = 0.002). Early relapse led to a shorter TTD than late relapse (P = 0.005). Median TTD was 14 months for patients who underwent salvage therapy and 2 months for untreated cases (P < 0.00001). A multivariate analysis showed an independent prognostic role for salvage therapy and time to relapse. Age and type of failure had no predictive value. Salvage therapy significantly improves outcome and, possibly, quality of life. As many different treatments were used conclusions cannot be made regarding an optimal treatment schedule. © 1999 Cancer Research Campaig

A Televised, Web-Based Randomised Trial of an Herbal Remedy (Valerian) for Insomnia

BACKGROUND: This trial was conducted as part of a project that aims to enhance public understanding and use of research in decisions about healthcare by enabling viewers to participate in research and to follow the process, through television reports and on the web. Valerian is an herbal over-the-counter drug that is widely used for insomnia. Systematic reviews have found inconsistent and inconclusive results about its effects. METHODS: Participants were recruited through a weekly nationally televised health program in Norway. Enrolment and data collection were over the Internet. 405 participants who were 18 to 75 years old and had insomnia completed a two week diary-keeping run-in period without treatment and were randomised and mailed valerian or placebo tablets for two weeks. All participants and investigators were blind to treatment until after the analysis was completed. FINDINGS: For the primary outcome of a minimally important improvement in self-reported sleep quality (> or = 0.5 units on a 7 point scale), the difference between the valerian group (29%) and the placebo group (21%) was not statistically significant (difference 7.5%; 95% CI-0.9 to 15.9; p = 0.08). On the global self-assessment question at the end of the treatment period 5.5% (95% CI 0.2 to 10.8) more participants in the valerian group perceived their sleep as better or much better (p = 0.04). There were similar trends favouring the valerian group for night awakenings (difference = 6.0%, 95% CI-0.5 to 12.5) and sleep duration (difference = 7.5%, 95% CI-1.0 to 16.1). There were no serious adverse events and no important or statistically significant differences in minor adverse events. INTERPRETATION: Based on this and previous studies, valerian appears to be safe, but with modest beneficial effects at most on insomnia compared to placebo. The combined use of television and the Internet in randomised trials offers opportunities to answer questions about the effects of health care interventions and to improve public understanding and use of randomised trials. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN72748991

Effects of Long-Term Space Flight on Erythrocytes and Oxidative Stress of Rodents

Erythrocyte and hemoglobin losses have been frequently observed in humans during space missions; these observations have been designated as “space anemia”. Erythrocytes exposed to microgravity have a modified rheology and undergo hemolysis to a greater extent. Cell membrane composition plays an important role in determining erythrocyte resistance to mechanical stress and it is well known that membrane composition might be influenced by external events, such as hypothermia, hypoxia or gravitational strength variations. Moreover, an altered cell membrane composition, in particular in fatty acids, can cause a greater sensitivity to peroxidative stress, with increase in membrane fragility. Solar radiation or low wavelength electromagnetic radiations (such as gamma rays) from the Earth or the space environment can split water to generate the hydroxyl radical, very reactive at the site of its formation, which can initiate chain reactions leading to lipid peroxidation. These reactive free radicals can react with the non-radical molecules, leading to oxidative damage of lipids, proteins and DNA, etiologically associated with various diseases and morbidities such as cancer, cell degeneration, and inflammation. Indeed, radiation constitutes on of the most important hazard for humans during long-term space flights. With this background, we participated to the MDS tissue-sharing program performing analyses on mice erythrocytes flown on the ISS from August to November 2009. Our results indicate that space flight induced modifications in cell membrane composition and increase of lipid peroxidation products, in mouse erythrocytes. Moreover, antioxidant defenses in the flight erythrocytes were induced, with a significant increase of glutathione content as compared to both vivarium and ground control erythrocytes. Nonetheless, this induction was not sufficient to prevent damages caused by oxidative stress. Future experiments should provide information helpful to reduce the effects of oxidative stress exposure and space anemia, possibly by integrating appropriate dietary elements and natural compounds that could act as antioxidants