Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold

Heterodimeric proteins with homologous subunits of same fold are involved in various biological processes. The objective of this study is to understand the evolution of structural and functional features of such heterodimers. Using a non-redundant dataset of 70 such heterodimers of known 3D structure and an independent dataset of 173 heterodimers from yeast, we note that the mean sequence identity between interacting homologous subunits is only 23-24% suggesting that, generally, highly diverged paralogues assemble to form such a heterodimer. We also note that the functional roles of interacting subunits/domains are generally quite different. This suggests that, though the interacting subunits/domains are homologous, the high evolutionary divergence characterize their high functional divergence which contributes to a gross function for the heterodimer considered as a whole. The inverse relationship between sequence identity and RMSD of interacting homologues in heterodimers is not followed. We also addressed the question of formation of homodimers of the subunits of heterodimers by generating models of fictitious homodimers on the basis of the 3D structures of the heterodimers. Interaction energies associated with these homodimers suggests that, in overwhelming majority of the cases, such homodimers are unlikely to be stable. Majority of the homologues of heterodimers of known structures form heterodimers (51.8%) and a small proportion (14.6%) form homodimers. Comparison of 3D structures of heterodimers with homologous homodimers suggests that interfacial nature of residues is not well conserved. In over 90% of the cases we note that the interacting subunits of heterodimers are co-localized in the cell. Proteins 2015; 83:1766-1786. (c) 2015 Wiley Periodicals, Inc.

Cyclic Cationic Peptides Containing Sugar Amino Acids Selectively Distinguishes and Inhibits Maturation of Pre-miRNAs of the Same Family

The discovery of microRNAs (miRNAs) has added a new dimension to the gene regulatory networks, making aberrantly expressed miRNAs as therapeutically important targets. Small molecules that can selectively target and modulate miRNA levels can thus serve as lead structures. Cationic cyclic peptides containing sugar amino acids represent a new class of small molecules that can target miRNA selectively. Upon treatment of these small molecules in breast cancer cell line, we profiled 96 therapeutically important miRNAs associated with cancer and observed that these peptides can selectively target paralogous miRNAs of the same seed family. This selective inhibition is of prime significance in cases when miRNAs of the same family have tissue-specific expression and perform different functions. During these conditions, targeting an entire miRNA family could lead to undesired adverse effects. The selective targeting is attributable to the difference in the three-dimensional structures of precursor miRNAs. Hence, the core structure of these peptides can be used as a scaffold for designing more potent inhibitors of miRNA maturation and hence function.

Comparison between weight loss of bends in a pneumatic conveyor and erosion rate obtained in a centrifugal erosion tester for the same materials

In order to find a link between results obtained from a laboratory erosion tester and tests carried out on a pneumatic conveyor, a comparison has been made between weight loss from bends on an industrial-scale pneumatic conveyor and erosion rates obtained in a small centrifugal erosion tester, for the same materials. Identical test conditions have been applied to both experiments so that comparable test results have been obtained. The erosion rate of mild steel commonly used as the wall material of conveyor pipes and pipe bends was determined individually on both test rigs. A relationship between weight loss from the bends and erosion rate determined from the tester has been developed. A discussion based on the results and their applicability to the prediction of wear in pneumatic conveyors concludes the paper. © 2004 Elsevier B.V. All rights reserved.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration. © 2011 Blackwell Publishing Ltd.

Dos asambleas sinodales y una misma meta : estudiar los desafíos pastorales sobre la familia en el contexto de la evangelización

Resumen: Para toda la Iglesia, el presente año se caracteriza por la preparación de un Sínodo de los obispos de tipo extraordinario que preparará uno ordinario para el año próximo. Esta novedad metodológica ayuda a repasar el mencionado instituto teológico que, gracias al último Concilio Ecuménico, hace cincuenta años reviste el carácter de permanente. Los temas a tratar persiguen un mismo fin: estudiar los desafíos pastorales sobre la familia en el contexto de la evangelización. Propuesto como tema, también es continuidad de un método pontificio que solicita caminar en conjunto con el colegio de los obispos y por ende con todo el Pueblo de Dios. Finalmente se hace una propuesta que ayude a mejorar la terminología para hablar de matrimonio y familia en orden a un mejor acompañamiento canónico y pastoral de todas las realidades.

Career Planning in Spain: Do temporary contracts delay marriage and motherhood?

The aim of this paper is to find an empirical connection between the impressive increase in the use of temporary contracts in Spain and the observed increase in age at marriage and maternity. Using a pool of the six available waves of individual information from the European Household Panel for Spain, we find that holding temporary contracts rather than permanent ones delays marriage for males, but not for females. Concerning maternity, the labor market situation of both members of the household affects entry into motherhood. In particular, if woman has a temporary contract rather than a permanent one, motherhoods is delayed independently of the husband's contract. As expected, postponement of maternity is not found for non-working women. These results give strong support to the career planning, motive to delay maternity in Spain, given that an unstable labor market situation of female workers is found to be the main deterrent to entry into motherhood.

El modelo de sexualidad de la sociedad cristiana medieval: norma y transgresión

[ES]En estas páginas se analiza el modelo de sexualidad conyugal establecido por la Iglesia medieval para poder responder a la pregunta de qué era lícito y qué no en las relaciones sexuales. Así, entre otras cuestiones, se pasa revista a las posturas, a los momentos, las frecuencias, etc. Igualmente se exponen diversas estrategias arbitradas por la sociedad medieval para vivir en pareja y disfrutar del sexo al margen del matrimonio canónico, como la barraganía,el amancebamiento o el estupro.

Purgatorio - two rather different views of the same event

Detailed description of plankton entrainment in power plant cooling systems.

Assessment of Atlantic Red Drum for 1999: Northern and southern regions

An assessment of the status of the Atlantic stock of red drum is conducted using recreational and commercial data from 1986 through 1998. This assessment updates data and analyses from the 1989, 1991, 1992 and 1995 stock assessments on Atlantic coast red drum (Vaughan and Helser, 1990; Vaughan 1992; 1993; 1996). Since 1981, coastwide recreational catches ranged between 762,300 pounds in 1980 and 2,623,900 pounds in 1984, while commercial landings ranged between 60,900 pounds in 1997 and 422,500 pounds in 1984. In weight of fish caught, Atlantic red drum constitute predominantly a recreational fishery (ranging between 85 and 95% during the 1990s). Commercially, red drum continue to be harvested as part of mixed species fisheries. Using available length-frequency distributions and age-length keys, recreational and commercial catches are converted to catch in numbers at age. Separable and tuned virtual population analyses are conducted on the catch in numbers at age to obtain estimates of fishing mortality rates and population size (including recruitment to age 1). In tum, these estimates of fishing mortality rates combined with estimates of growth (length and weight), sex ratios, sexual maturity and fecundity are used to estimate yield per recruit, escapement to age 4, and static (or equilibrium) spawning potential ratio (static SPR, based on both female biomass and egg production). Three virtual analysis approaches (separable, spreadsheet, and FADAPT) were applied to catch matrices for two time periods (early: 1986-1991, and late: 1992-1998) and two regions (Northern: North Carolina and north, and Southern: South Carolina through east coast of Florida). Additional catch matrices were developed based on different treatments for the catch-and-release recreationally-caught red drum (B2-type). These approaches included assuming 0% mortality (BASEO) versus 10% mortality for B2 fish. For the 10% mortality on B2 fish, sizes were assumed the same as caught fish (BASEl), or positive difference in size distribution between the early period and the later period (DELTA), or intermediate (PROP). Hence, a total of 8 catch matrices were developed (2 regions, and 4 B2 assumptions for 1986-1998) to which the three VPA approaches were applied. The question of when offshore emigration or reduced availability begins (during or after age 3) continues to be a source of bias that tends to result in overestimates of fishing mortality. Additionally, the continued assumption (Vaughan and Helser, 1990; Vaughan 1992; 1993; 1996) of no fishing mortality on adults (ages 6 and older), causes a bias that results in underestimates of fishing mortality for adult ages (0 versus some positive value). Because of emigration and the effect of the slot limit for the later period, a range in relative exploitations of age 3 to age 2 red drum was considered. Tuning indices were developed from the MRFSS, and state indices for use in the spreadsheet and FADAPT VPAs. The SAFMC Red Drum Assessment Group (Appendix A) favored the FADAPT approach with catch matrix based on DELTA and a selectivity for age 3 relative to age 2 of 0.70 for the northern region and 0.87 for the southern region. In the northern region, estimates of static SPR increased from about 1.3% for the period 1987-1991 to approximately 18% (15% and 20%) for the period 1992-1998. For the southern region, estimates of static SPR increased from about 0.5% for the period 1988-1991 to approximately 15% for the period 1992-1998. Population models used in this assessment (specifically yield per recruit and static spawning potential ratio) are based on equilibrium assumptions: because no direct estimates are available as to the current status of the adult stock, model results imply potential longer term, equilibrium effects. Because current status of the adult stock is unknown, a specific rebuilding schedule cannot be determined. However, the duration of a rebuilding schedule should reflect, in part, a measure of the generation time of the fish species under consideration. For a long-lived, but relatively early spawning, species as red drum, mean generation time would be on the order of 15 to 20 years based on age-specific egg production. Maximum age is 50 to 60 years for the northern region, and about 40 years for the southern region. The ASMFC Red Drum Board's first phase recovery goal of increasing %SPR to at least 10% appears to have been met. (PDF contains 79 pages)

Second-to-Fourth Digit Ratio Has a Non-Monotonic Impact on Altruism

Gene-culture co-evolution emphasizes the joint role of culture and genes for the emergence of altruistic and cooperative behaviors and behavioral genetics provides estimates of their relative importance. However, these approaches cannot assess which biological traits determine altruism or how. We analyze the association between altruism in adults and the exposure to prenatal sex hormones, using the second-to-fourth digit ratio. We find an inverted U-shaped relation for left and right hands, which is very consistent for men and less systematic for women. Subjects with both high and low digit ratios give less than individuals with intermediate digit ratios. We repeat the exercise with the same subjects seven months later and find a similar association, even though subjects' behavior differs the second time they play the game. We then construct proxies of the median digit ratio in the population (using more than 1000 different subjects), show that subjects' altruism decreases with the distance of their ratio to these proxies. These results provide direct evidence that prenatal events contribute to the variation of altruistic behavior and that the exposure to fetal hormones is one of the relevant biological factors. In addition, the findings suggest that there might be an optimal level of exposure to these hormones from social perspective.

A preliminary investigation into the effects of a sex-reversal androgen, methyltestosterone, on food utilization and growth of Sarotherodon niloticus (L) fry

Three groups of Sarotherodon niloticus fry were fed for 8 weeks on diets either treated with 17- & methyltestosterone (MT), alcohol (CA), or untreated (CO). Growth rate and food utilization in the different groups were compared. Results indicate that the best growth, Feed Conversion Ratio (FCR), Protein Efficiency Ratio (PER) and Mean Growth Rate (MGR) were obtained with the MT diet. There was no significant difference (P 0.05) in growth and food utilization of the CA and CO fry, nor in the mortality rate of the 3 treatments. The androgen, methyltestosterone promotes growth and protein anabolism without producing toxic effects in S. niloticus