The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Deep Sequencing Analyses of Low Density Microbial Communities: Working at the Boundary of Accurate Microbiota Detection

Introduction: Accurate analyses of microbiota composition of low-density communities (10 3 –10 4 bacteria/sample) can be challenging. Background DNA from chemicals and consumables, extraction biases as well as differences in PCR efficiency can significantly interfere with microbiota assessment. This study was aiming to establish protocols for accurate microbiota analysis at low microbial density. Methods: To examine possible effects of bacterial density on microbiota analyses we compared microbiota profiles of seria

The Transcriptional Response in Human Umbilical Vein Endothelial Cells Exposed to Insulin: A Dynamic Gene Expression Approach

BACKGROUND: In diabetes chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation through the activation of the MAP kinases, which in turn regulate cellular proliferation. However, it is not known whether insulin itself could increase the transcription of specific genes for cellular proliferation in the endothelium. Hence, the characterization of transcriptional modifications in endothelium is an important step for a better understanding of the mechanism of insulin action and the relationship between endothelial cell dysfunction and insulin resistance. METHODOLOGY AND PRINCIPAL FINDINGS: The transcriptional response of endothelial cells in the 440 minutes following insulin stimulation was monitored using microarrays and compared to a control condition. About 1700 genes were selected as differentially expressed based on their treated minus control profile, thus allowing the detection of even small but systematic changes in gene expression. Genes were clustered in 7 groups according to their time expression profile and classified into 15 functional categories that can support the biological effects of insulin, based on Gene Ontology enrichment analysis. In terms of endothelial function, the most prominent processes affected were NADH dehydrogenase activity, N-terminal myristoylation domain binding, nitric-oxide synthase regulator activity and growth factor binding. Pathway-based enrichment analysis revealed "Electron Transport Chain" significantly enriched. Results were validated on genes belonging to "Electron Transport Chain" pathway, using quantitative RT-PCR. CONCLUSIONS: As far as we know, this is the first systematic study in the literature monitoring transcriptional response to insulin in endothelial cells, in a time series microarray experiment. Since chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction

Nitrogen stable isotopes indicate differences in nitrogen cycling between two contrasting Jamaican montane forests

Background and aims The aim of this study is to enhance our knowledge of nitrogen (N) cycling and N acquisition in tropical montane forests through analysis of stable N isotopes (δ15N). Methods Leaves from eight common tree species, leaf litter, soils from three depths and roots were sampled from two contrasting montane forest types in Jamaica (mull ridge and mor ridge) and were analysed for δ15N. Results All foliar δ15N values were negative and varied among the tree species but were significantly more negative in the mor ridge forest (by about 2 ‰). δ15N of soils and roots were also more negative in mor ridge forests by about 3 ‰. Foliar δ15N values were closer to that of soil ammonium than soil nitrate suggesting that trees in these forests may have a preference for ammonium; this may explain the high losses of nitrate from similar tropical montane forests. There was no correlation between the rankings of foliar δ15N in the two forest types suggesting a changing uptake ratio of different N forms between forest types. Conclusions These results indicate that N is found at low concentrations in this ecosystem and that there is a tighter N cycle in the mor ridge forest, confirmed by reduced nitrogen availability and lower rates of nitrification. Overall, soil or root δ15N values are more useful in assessing ecosystem N cycling patterns as different tree species showed differences in foliar δ15N between the two forest types

The great melting pot. Common sole population connectivity assessed by otolith and water fingerprints

Quantifying the scale and importance of individual dispersion between populations and life stages is a key challenge in marine ecology. The common sole (Solea solea), an important commercial flatfish in the North Sea, Atlantic Ocean and the Mediterranean Sea, has a marine pelagic larval stage, a benthic juvenile stage in coastal nurseries (lagoons, estuaries or shallow marine areas) and a benthic adult stage in deeper marine waters on the continental shelf. To date, the ecological connectivity among these life stages has been little assessed in the Mediterranean. Here, such an assessment is provided for the first time for the Gulf of Lions, NW Mediterranean, based on a dataset on otolith microchemistry and stable isotopic composition as indicators of the water masses inhabited by individual fish. Specifically, otolith Ba/Ca and Sr/Ca profiles, and delta C-13 and delta O-18 values of adults collected in four areas of the Gulf of Lions were compared with those of young-of-the-year collected in different coastal nurseries. Results showed that a high proportion of adults (>46%) were influenced by river inputs during their larval stage. Furthermore Sr/Ca ratios and the otolith length at one year of age revealed that most adults (similar to 70%) spent their juvenile stage in nurseries with high salinity, whereas the remainder used brackish environments. In total, data were consistent with the use of six nursery types, three with high salinity (marine areas and two types of highly saline lagoons) and three brackish (coastal areas near river mouths, and two types of brackish environments), all of which contributed to the replenishment of adult populations. These finding implicated panmixia in sole population in the Gulf of Lions and claimed for a habitat integrated management of fisherie

Co-resident Parents and Young People Aged 15–34: Who Does What Housework?

Young adults are now more likely to co-reside with their parents than previous generations, but domestic work patterns among this family type are largely unexplored. This study addresses this issue using Australian Bureau of Statistics Time Use Surveys (1992, 1997, 2006) and Poisson–Gamma regression analyses. It examines patterns in and correlates of domestic labor in two-generation households in which young people aged 15–34 co-reside with their parents (n = 1,946 households comprised of 2,806 young people and 5,129 parents). It differentiates between routine indoor tasks (cooking, cleaning, laundry), non-routine tasks (outdoor work, household management and maintenance, car care) and grocery shopping. Predictors of more time in some domestic activities by young people include being in neither employment nor education/training (NEET), being older, having a single parent and being in a non-English speaking household (young women). Young people being NEET, or female, are associated with less cooking time for mothers, but in the main when young people do perform domestic activities, they do not relieve their parents of those same activities, suggesting more time is spent by the household in total

Life History of Female Preferences for Male Faces: A Comparison of Pubescent Girls, Nonpregnant and Pregnant Young Women, and Middle-aged Women

Although scientific interest in facial attractiveness has developed substantially in recent years, few studies have contributed to our understanding of the ontogeny of facial preferences. In this study, attractiveness of 30 male faces was evaluated by four female groups: girls at puberty, nonpregnant and pregnant young women, and middle-aged women. The main findings are as follows: (1) Preference for sexy-looking faces was strongest in young, nonpregnant women. (2) Biologically more mature girls displayed more adultlike preferences. (3) The intragroup consistency for postmenopausal women was relatively low. (4) In terms of the preference pattern, pregnant women were more similar to perimenopausal women than they were to their nonpregnant peers. (5) Preference for youthful appearance decreased with the age of the women. I argue that the life history of female preferences for male faces is, to a large extent, hormone-driven and underpinned by a set of evolutionary adaptations

Bayesian Computation with Intractable Likelihoods

This article surveys computational methods for posterior inference with intractable likelihoods, that is where the likelihood function is unavailable in closed form, or where evaluation of the likelihood is infeasible. We review recent developments in pseudo-marginal methods, approximate Bayesian computation (ABC), the exchange algorithm, thermodynamic integration, and composite likelihood, paying particular attention to advancements in scalability for large datasets. We also mention R and MATLAB source code for implementations of these algorithms, where they are available.Comment: arXiv admin note: text overlap with arXiv:1503.0806