Smaller Genetic Risk in Catabolic Process Explains Lower Energy Expenditure, More Athletic Capability and Higher Prevalence of Obesity in Africans

Lower energy expenditure (EE) for physical activity was observed in Africans than in Europeans, which might contribute to the higher prevalence of obesity and more athletic capability in Africans. But it is still unclear why EE is lower among African populations. In this study we tried to explore the genetic mechanism underlying lower EE in Africans. We screened 231 common variants with possibly harmful impact on 182 genes in the catabolic process. The genetic risk, including the total number of mutations and the sum of harmful probabilities, was calculated and analyzed for the screened variants at a population level. Results of the genetic risk among human groups showed that most Africans (3 out of 4 groups) had a significantly smaller genetic risk in the catabolic process than Europeans and Asians, which might result in higher efficiency of generating energy among Africans. In sport competitions, athletes need massive amounts of energy expenditure in a short period of time, so higher efficiency of energy generation might help make African-descendent athletes more powerful. On the other hand, higher efficiency of generating energy might also result in consuming smaller volumes of body mass. As a result, Africans might be more vulnerable to obesity compared to the other races when under the same or similar conditions. Therefore, the smaller genetic risk in the catabolic process might be at the core of understanding lower EE, more athletic capability and higher prevalence of obesity in Africans

Computing Tate-Shafarevich groups of multinorm one tori of Kummer type

A multinorm one torus associated to a commutative \'etale algebra $L$ over a global field $k$ is of Kummer type if each factor of $L$ is a cyclic Kummer extension. In this paper we compute the Tate-Shafarevich group of such tori based on recent works of Bayer-Fluckiger, T.-Y. Lee and Parimala, and of T.-Y.~Lee. We also implement an effective algorithm using SAGE which computes the Tate-Shafarevich groups when each factor of $L$ is contained in a fixed concrete bicyclic extension of $k$.Comment: 17 pages, 3 figures, comments are welcom

Moderate mutation rate in the SARS coronavirus genome and its implications

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic

ISG15 inhibits IFN- a -Resistant liver cancer cell growth

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide. Interferon-a (IFN-a) has been widely used in the treatment of HCC, but patients eventually develop resistance. ISG15 ubiquitin-like modifier (ISG15) is a ubiquitin-like protein transcriptionally regulated by IFN-a which shows antivirus and antitumor activities. However, the exact role of ISG15 is unknown. In the present study, we showed that IFN-a significantly induced ISG15 expression but failed to induce HepG2 cell apoptosis, whereas transient overexpression of ISG15 dramatically increased HepG2 cell apoptosis. ISG15 overexpression increased overall protein ubiquitination, which was not observed in cells with IFN-a-induced ISG15 expression, suggesting that IFN-a treatment not only induced the expression of ISG15 but also inhibited ISG15-mediated ubiquitination. The tumor suppressor p53 and p21 proteins are the key regulators of cell survival and death in response to stress signals such as DNA damage. We showed that p53 or p21 is only up regulated in HepG2 cells ectopically expressing ISG15, but not in the presence of IFN-a-induced ISG15. Our results suggest that ISG15 overexpression could be developed into a powerful gene-therapeutic tool for treating IFN-a-resistant HCC. © 2013 Xin-xing Wan et al

Global expression profiling reveals genetic programs underlying the developmental divergence between mouse and human embryogenesis

BACKGROUND: Mouse has served as an excellent model for studying human development and diseases due to its similarity to human. Advances in transgenic and knockout studies in mouse have dramatically strengthened the use of this model and significantly improved our understanding of gene function during development in the past few decades. More recently, global gene expression analyses have revealed novel features in early embryogenesis up to gastrulation stages and have indeed provided molecular evidence supporting the conservation in early development in human and mouse. On the other hand, little information is known about the gene regulatory networks governing the subsequent organogenesis. Importantly, mouse and human development diverges during organogenesis. For instance, the mouse embryo is born around the end of organogenesis while in human the subsequent fetal period of ongoing growth and maturation of most organs spans more than 2/3 of human embryogenesis. While two recent studies reported the gene expression profiles during human organogenesis, no global gene expression analysis had been done for mouse organogenesis. RESULTS: Here we report a detailed analysis of the global gene expression profiles from egg to the end of organogenesis in mouse. Our studies have revealed distinct temporal regulation patterns for genes belonging to different functional (Gene Ontology or GO) categories that support their roles during organogenesis. More importantly, comparative analyses identify both conserved and divergent gene regulation programs in mouse and human organogenesis, with the latter likely responsible for the developmental divergence between the two species, and further suggest a novel developmental strategy during vertebrate evolution. CONCLUSIONS: We have reported here the first genome-wide gene expression analysis of the entire mouse embryogenesis and compared the transcriptome atlas during mouse and human embryogenesis. Given our earlier observation that genes function in a given process tends to be developmentally co-regulated during organogenesis, our microarray data here should help to identify genes associated with mouse development and/or infer the developmental functions of unknown genes. In addition, our study might be useful for invesgtigating the molecular basis of vertebrate evolution

Exploring the role of indoor microbiome and environmental characteristics in rhinitis symptoms among university students

IntroductionRhinitis is one of the most prevalent chronic respiratory diseases worldwide. There is emerging evidence suggesting that the indoor microbiome may contribute the onset and exacerbation of rhinitis symptoms, but comprehensive studies on this topic remain scarce.MethodsIn this study, we assessed the microbiome assemblage of settled air dust collected in Petri dishes in 86 dormitory rooms of Shanxi University, China using 16s rRNA sequencing. A self-administered questionnaire, including questions about rhinitis symptoms and personal information, was completed by 357 students residing in these dormitories. Logistic and linear regression model was applied to examine the associations between environmental characteristics, indoor microbiome, and rhinitis.ResultsThe most abundant genera in the dormitories were Ralstonia (15.6%), Pelomonas (11.3%), Anoxybacillus (9.3%) and Ochrobactrum (6.2%). Taxa richness in the class of Actinobacteria and Fusobacteriia was negatively/protectively associated with rhinitis (p<0.05). Six bacterial genera, including those from Actinobacteria (Actinomyces), Fusobacteriia (Fusobacterium), and Bacteroidetes (Prevotella and Capnocytophaga), were negatively/protectively associated with rhinitis. Conversely, seven genera, predominantly from Alphaproteobacteria and Betaproteobacteria (Sphingomonas, Caulobacter, uncharacterized Caulobacteraceae and Comamonadaceae), were positively associated with rhinitis. Living in higher floor level and higher indoor PM2.5 concentrations were associated with a higher abundance of taxa potentially protective against rhinitis and a lower abundance of taxa potentially increasing the risk of rhinitis (P<0.01). However, having curtain indoor and higher indoor CO2 concentrations were associated with a lower abundance of taxa potentially protective against rhinitis and a higher abundance of taxa potentially increasing the risk of rhinitis (P<0.01).DiscussionThis study enhances our understanding of the complex interactions between environmental characteristics, indoor microbiomes, and rhinitis, shedding light on potential strategies to manipulate indoor microbiome for disease prevention and control