Predicting the phenotypic effects of non-synonymous single nucleotide polymorphisms based on support vector machines

<p>Abstract</p> <p>Background</p> <p>Human genetic variations primarily result from single nucleotide polymorphisms (SNPs) that occur approximately every 1000 bases in the overall human population. The non-synonymous SNPs (nsSNPs) that lead to amino acid changes in the protein product may account for nearly half of the known genetic variations linked to inherited human diseases. One of the key problems of medical genetics today is to identify nsSNPs that underlie disease-related phenotypes in humans. As such, the development of computational tools that can identify such nsSNPs would enhance our understanding of genetic diseases and help predict the disease.</p> <p>Results</p> <p>We propose a method, named Parepro (Predicting the amino acid replacement probability), to identify nsSNPs having either deleterious or neutral effects on the resulting protein function. Two independent datasets, HumVar and NewHumVar, taken from the PhD-SNP server, were applied to train the model and test the robustness of Parepro. Using a 20-fold cross validation test on the HumVar dataset, Parepro achieved a Matthews correlation coefficient (MCC) of 50% and an overall accuracy (Q2) of 76%, both of which were higher than those predicted by the methods, such as PolyPhen, SIFT, and HydridMeth. Further analysis on an additional dataset (NewHumVar) using Parepro yielded similar results.</p> <p>Conclusion</p> <p>The performance of Parepro indicates that it is a powerful tool for predicting the effect of nsSNPs on protein function and would be useful for large-scale analysis of genomic nsSNP data.</p

The Research of Design Based on Social Commerce

Based on previous design theories which focus only on artifacts, we study the factors of social commerce design with application environment and human capabilities. By comparing social commerce design model and information model, we develop a new social commerce design model, further exploring user requirements after shopping, including the exploration of brand community, sharing offline social shopping experience and the improvement of user social skills. According to the new model, we revealed the common features of social commerce design, including the individual, conversation, community, commerce and management levels. Besides, this paper pointed out social commerce design research problems in future

Effects of Mongolian Medicine Modified Sugmul-7 on Hyperplasia of the Breast

Objectives: The aim of this study was to explore the mechanism of regulating the endocrine function of hyperplasia breast in rats with Mongolian Medicine Modified Sugmul-7 (MMMS-7) by Proteomics and provide an experimental basis for its development and clinical application. Methods: Ninety female SD rats were randomly divided into 6 groups: the intact group – the animal group that was injected with neither estradiol, nor progesterone, nor administered Mongolian Medicine Modified Sugmul-7; the negative control group – the group injected with estradiol and progesterone; the positive control group - injected with estradiol, progesterone and administered mastodynon 0.06 g/kg; and the treatment groups – injected with estradiol and progesterone, each in their respective dose groups. After the start of the experiment, each rat except the intact group was intra peritoneally injected with estradiol 25d and progesterone 6d at a standard dose of 0.3 mg / kg for a total of 31 days. Results: Four differential proteins were found through proteomic analysis, namely Ppp3cb, Cacybp, Gstz1, and Nmd3 and their 5 related pathways. Conclusions: The above pathways are all known to be related to the treatment of breast hyperplasia caused by endocrine disorders. Treatment with Mongolian Medicine Modified Sugmul-7 is completed through regulation of the gastrointestinal and endocrine systems

A general model of hormesis in biological systems and its application to pest management

Hormesis, a phenomenon whereby exposure to high levels of stressors is inhibitory but low (mild, sublethal and subtoxic) doses are stimulatory, challenges decision-making in the management of cancer, neurodegenerative diseases, nutrition and ecotoxicology. In the latter, increasing amounts of a pesticide may lead to upsurges rather than declines of pests, ecological paradoxes that are difficult to predict. Using a novel re-formulation of the Ricker population equation, we show how interactions between intervention strengths and dose timings, dose–response functions and intrinsic factors can model such paradoxes and hormesis. A model with three critical parameters revealed hormetic biphasic dose and dose timing responses, either in a J-shape or an inverted U-shape, yielding a homeostatic change or a catastrophic shift and hormetic effects in many parameter regions. Such effects were enhanced by repeated pulses of low-level stimulations within one generation at different dose timings, thereby reducing threshold levels, maximum responses and inhibition. The model provides insights into the complex dynamics of such systems and a methodology for improved experimental design and analysis, with wide-reaching implications for understanding hormetic effects in ecology and in medical and veterinary treatment decision-making. We hypothesized that the dynamics of a discrete generation pest control system can be determined by various three parameter spaces, some of which reveal the conditions for occurrence of hormesis, and confirmed this by fitting our model to both hormetic data from the literature and to a non-hormetic dataset on pesticidal control of mirid bugs in cotton

Reconversión laboral del sector agropecuario hacia el turismo. Desafíos para la Patagonia chilena

[EN] The development of tourism can help to diversify the productive matrix and reduce rural depopulation. This study analyzes the possibility of agricultural worker participation in the tourism sector in rural areas of Chilean Patagonia. Based on the 2017 CASEN survey, data matching and estimation of logit model are conducted to evaluate the probability of agricultural worker reconversion. The results indicate that the proportion of agricultural workers who can move to tourism is low. However, women and individuals with post-secondary education are more likely to be reconverted.[ES] La actividad turística puede ayudar a diversificar la matriz productiva y reducir el despoblamiento rural. Este estudio analiza la posibilidad de participación de trabajadores agropecuarios en el sector turismo en las zonas rurales de la Patagonia Chilena. Usando la encuesta CASEN del año 2017, se realiza un proceso de emparejamiento de datos (matching) y la estimación de un modelo logit para evaluar la probabilidad de reconversión laboral. Los resultados indican que hay una baja proporción de trabajadores que puedan transitar hacia el sector turismo. Sin embargo, las mujeres y los individuos con estudios postsecundarios tienen mayores probabilidades de reconversión.Este trabajo está enmarcado dentro del proyecto de investigación “La Vocación Productiva, el Nivel Educativo y la Funcionalidad del Centro Emisor y Receptor como Factores Explicativos de la Conmutación Inter e Intrarregional en la Región de los Andes Australes de la Patagonia Chilena”, financiado por CONICYT (Proyecto Fondecyt Número 1160196), por lo que los autores agradecen dichos aportes.Mancilla, C.; Ferrada, LM.; Soza-Amigo, S. (2019). Labour reconversion of the agricultural sector towards tourism. Challenges for Chilean Patagonia. Economía Agraria y Recursos Naturales - Agricultural and Resource Economics. 19(1):175-194. https://doi.org/10.7201/earn.2019.01.0917519419

Omega-6 Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of Individual-Level Data for 39 740 Adults from 20 Prospective Cohort Studies

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m(2), who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72,

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention