Computational Study of Evolutionary Selection Pressure on Rainbow Trout Estrogen Receptors

Molecular dynamics simulations were used to determine the binding affinities between the hormone 17-estradiol (E2) and different estrogen receptor (ER) isoforms in the rainbow trout, Oncorhynchus mykiss. Previous phylogenetic analysis indicates that a whole genome duplication prior to the divergence of ray-finned fish led to two distinct ER isoforms, ER and ER, and the recent whole genome duplication in the ancestral salmonid created two ER isoforms, ER and ER. The objective of our computational studies is to provide insight into the underlying evolutionary pressures on these isoforms. For the ER subtype our results show that E2 binds preferentially to ER over ER. Tests of lineage specific N/S ratios indicate that the ligand binding domain of the ER gene is evolving under relaxed selection relative to all other ER genes. Comparison with the highly conserved DNA binding domain suggests that ER may be undergoing neofunctionalization possibly by binding to another ligand. By contrast, both ER and ER bind similarly to E2 and the best fitting model of selection indicates that the ligand binding domain of all ER genes are evolving under the same level of purifying selection, comparable to ER

Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk.

Background: The late endosomal LAMTOR complex serves as a convergence point for both the RAF/MEK/ERK and the PI3K/AKT/mTOR pathways. Interestingly, both of these signalling cascades play a significant role in the aetiology of breast cancer. Our aim was to address the possible role of genetic polymorphisms in LAMTOR2 and LAMTOR3 as genetic risk factors for breast cancer. Methodology/Results: We sequenced the exons and exon-intron boundaries of LAMTOR2 (p14) and LAMTOR3 (MP1) in 50 prospectively collected pairs of cancerous tissue and blood samples from breast cancer patients and compared their genetic variability. We found one single nucleotide polymorphism (SNP) in LAMTOR2 (rs7541) and two SNPs in LAMTOR3 (rs2298735 and rs148972953) in both tumour and blood samples, but no somatic mutations in cancerous tissues. In addition, we genotyped all three SNPs in 296 samples from the Risk Prediction of Breast Cancer Metastasis Study and found evidence of a genetic association between rs148972953 and oestrogen (ER) and progesterone receptor negative status (PR) (ER: OR = 3.60 (1.15-11.28); PR: OR = 4.27 (1.43-12.72)). However, when we additionally genotyped rs148972953 in the MARIE study including 2,715 breast cancer cases and 5,216 controls, we observed neither a difference in genotype frequencies between patients and controls nor was the SNP associated with ER or PR. Finally, all three SNPs were equally frequent in breast cancer samples and female participants (n = 640) of the population-based SAPHIR Study. Conclusions: The identified polymorphisms in LAMTOR2 and LAMTOR3 do not seem to play a relevant role in breast cancer. Our work does not exclude a role of other not yet identified SNPs or that the here annotated polymorphism may in fact play a relevant role in other diseases. Our results underscore the importance of replication in association studies

Friends and Foes from an Ant Brain's Point of View – Neuronal Correlates of Colony Odors in a Social Insect

Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ‘‘friend’’ and ‘‘foe’’ are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors

Drone aggregation behavior in the social wasp Vespula germanica (Hymenoptera: Vespidae): Effect of kinship and density

Inbreeding can have negative consequences on population viability because of the reduced fitness of the progeny. In general, most species have developed mechanisms to minimize inbreeding such as dispersal and kin avoidance behavior. In the eusocial Hymenoptera, related individuals typically share a common nest and have relatively short mating periods, this could lead to inbreeding, and because of their single?locus complementary sex determination system, it may generate diploid males that could result in infertile triploid progeny representing a cost for the colony. Vespula germanica, is an eusocial wasp that has invaded many parts of the world, despite likely facing a reduced genetic pool during the arrival phases. We ask whether male wasp display specific aggregation behavior that favors genetic diversity, key to reduce inbreeding. Through a set of laboratory experiments, we investigated the effects of drone nestmateship and density on the aggregation behavior of V. germanica drones. We show that drones avoid aggregating with their nestmates at all densities while non-nestmates are avoided only at high densities. This suggests that lek genetic diversity and density could be regulated through drone behavior and in the long run minimize inbreeding favoring invasion success.Fil: Masciocchi, Maité. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Angeletti, Bárbara. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Corley, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Martinez Von Ellrichshausen, Andres Santiago. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; Argentin

The null hypothesis significance test in health sciences research (1995-2006): statistical analysis and interpretation

<p>Abstract</p> <p>Background</p> <p>The null hypothesis significance test (NHST) is the most frequently used statistical method, although its inferential validity has been widely criticized since its introduction. In 1988, the <it>International Committee of Medical Journal Editors </it>(ICMJE) warned against sole reliance on NHST to substantiate study conclusions and suggested supplementary use of confidence intervals (CI). Our objective was to evaluate the extent and quality in the use of NHST and CI, both in English and Spanish language biomedical publications between 1995 and 2006, taking into account the <it>International Committee of Medical Journal Editors </it>recommendations, with particular focus on the accuracy of the interpretation of statistical significance and the validity of conclusions.</p> <p>Methods</p> <p>Original articles published in three English and three Spanish biomedical journals in three fields (General Medicine, Clinical Specialties and Epidemiology - Public Health) were considered for this study. Papers published in 1995-1996, 2000-2001, and 2005-2006 were selected through a systematic sampling method. After excluding the purely descriptive and theoretical articles, analytic studies were evaluated for their use of NHST with P-values and/or CI for interpretation of statistical "significance" and "relevance" in study conclusions.</p> <p>Results</p> <p>Among 1,043 original papers, 874 were selected for detailed review. The exclusive use of P-values was less frequent in English language publications as well as in Public Health journals; overall such use decreased from 41% in 1995-1996 to 21% in 2005-2006. While the use of CI increased over time, the "significance fallacy" (to equate statistical and substantive significance) appeared very often, mainly in journals devoted to clinical specialties (81%). In papers originally written in English and Spanish, 15% and 10%, respectively, mentioned statistical significance in their conclusions.</p> <p>Conclusions</p> <p>Overall, results of our review show some improvements in statistical management of statistical results, but further efforts by scholars and journal editors are clearly required to move the communication toward ICMJE advices, especially in the clinical setting, which seems to be imperative among publications in Spanish.</p