Interrogating eleven fast-evolving genes for signatures of recent positive selection in worldwide human populations

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs inchimpanzee, mouse, rat and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes were then further explored for signatures of recent positive selection using SNP data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP Diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintainance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal ofrecent selection in this region may come from a different, neighbouring gene (CD5) ratherthan from the candidate gene itself (VPS37C). For this set of positively-selected genes in thehuman lineage, we find no indication that these genes maintained their rapid evolutionarypace among human populations. Based on these data, it therefore appears that adaptation forhuman-specific and for population-specific traits may have involved different genes.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

Positive time-frequency distributions based on joint marginal constraints

This correspondence studies the formulation of members ofthe Cohen-Posch class of positive time-frequency energy distributions.Minimization of cross-entropy measures with respect to different priorsand the case of no prior or maximum entropy were considered. It isconcluded that, in general, the information provided by the classicalmarginal constraints is very limited, and thus, the final distributionheavily depends on the prior distribution. To overcome this limitation,joint time and frequency marginals are derived based on a "directioninvariance" criterion on the time-frequency plane that are directly relatedto the fractional Fourier transform.

Personality and job stress: a comparison of direct effects on parenting

The impact of personality and job characteristics on parental rearing styles was compared in 353 employees. Hypotheses concerning the relationships between personality and job variables were formulated in accordance with findings in past research and the Belsky’s model (1984). Structural equation nested models showed that Aggression-hostility, Sociability and job Demand were predictive of Rejection and Emotional Warmth parenting styles, providing support for some of the hypothesized relationships. The findings suggest a well-balanced association of personality variables with both parenting styles: Aggression-Hostility was positively related to Rejection and negatively to Emotional Warmth, whereas Sociability was positively related to Emotional Warmth and negatively related to Rejection. Personality dimensions explained a higher amount of variance in observed parenting styles. However, a model that considered both, personality and job dimensions as antecedent variables of parenting was the best representation of observed data, as both systems play a role in the prediction of parenting behavior.

The SUD1 Gene Encodes a Putative E3 Ubiquitin Ligase and Is a Positive Regulator of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Arabidopsis

The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the major rate-limiting step of the mevalonic acid (MVA) pathway from which sterols and other isoprenoids are synthesized. In contrast with our extensive knowledge of the regulation of HMGR in yeast and animals, little is known about this process in plants. To identify regulatory components of the MVA pathway in plants, we performed a genetic screen for second-site suppressor mutations of the Arabidopsis thaliana highly drought-sensitive drought hypersensitive2 (dry2) mutant that shows decreased squalene epoxidase activity. We show that mutations in SUPPRESSOR OF DRY2 DEFECTS1 (SUD1) gene recover most developmental defects in dry2 through changes in HMGR activity. SUD1 encodes a putative E3 ubiquitin ligase that shows sequence and structural similarity to yeast Degradation of a factor (Doa10) and human TEB4, components of the endoplasmic reticulum-associated degradation C (ERAD-C) pathway. While in yeast and animals, the alternative ERAD-L/ERAD-M pathway regulates HMGR activity by controlling protein stability, SUD1 regulates HMGR activity without apparent changes in protein content. These results highlight similarities, as well as important mechanistic differences, among the components involved in HMGR regulation in plants, yeast, and animals.

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.

Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs positive selection in Drosophila melanogaster.

In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events.

Assessing positive mental health in people with chronic physical health problems: correlations with socio-demographic variables and physical health status

Background: A holistic perspective on health implies giving careful consideration to the relationship between physical and mental health. In this regard the present study sought to determine the level of Positive Mental Health (PMH) among people with chronic physical health problems, and to examine the relationship between the observed levels of PMH and both physical health status and socio-demographic variables. Methods: The study was based on the Multifactor Model of Positive Mental Health (Lluch, 1999), which comprises six factors: Personal Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4), Problem-solving and Self-actualization (F5), and Interpersonal Relationship Skills (F6). The sample comprised 259 adults with chronic physical health problems who were recruited through a primary care center in the province of Barcelona (Spain). Positive mental health was assessed by means of the Positive Mental Health Questionnaire (Lluch, 1999). Results: Levels of PMH differed, either on the global scale or on specific factors, in relation to the following variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b) gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002), while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007); c) number of health conditions: the fewer the number of health problems the higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication: polymedication patients had lower PMH scores, both globally and on various factors; e) use of analgesics: occasional use of painkillers was associated with higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant differences in global PMH scores according to the type of chronic health condition. The only significant difference in the analysis by factors was that patients with hypertension obtained lower PMH scores on the factor Autonomy (t=2.165; p=0.032). Conclusions: Most people with chronic physical health problems have medium or high levels of PMH. The variables that adversely affect PMH are old age, polypharmacy and frequent consumption of analgesics. The type of health problem does not influence the levels of PMH. Much more extensive studies with samples without chronic pathology are now required in order to be able to draw more robust conclusions.

Recerca avaluativa sobre el programa “LÍMITS”

Des de la comunitat científica s’ha posat de manifest la necessitat d’avaluar els programes d’intervenció per a la millora de la parentalitat, especialment en el context de la infància i adolescència en risc. En aquesta recerca es presenten els resultats de l’avaluació del programa Límits aportant evidències d’eficàcia i efectivitat, que permeten identificar i descriure les seves fortaleses, així com també aquells elements que poden ser objecte de millora. El programa Límits és una proposta estructurada d’intervenció preventiva de caire selectiu amb grups de famílies de joves d’entre 14 i 18 anys que passen pel circuit de la justícia juvenil. El programa ha estat funcionant des del 2007, en diverses edicions, a tot el territori català aplegant una experiència i trajectòria remarcable que ha incidit en 351 persones i 245 famílies. El programa consta de vuit sessions en grup d’entre dotze i quinze participants, dinamitzat per dos monitors, en les que es treballen diferents estratègies a partir de l’abordatge de continguts relacionats amb les relacions i els lligams, la comunicació, els conflictes, l’establiment de normes i la disciplina. Per dur a terme l’avaluació del programa Límits s’ha partit d’un disseny quasi-experimental, pretest–postest aplicat a un grup programa (GP) i a grup col·laborador (GC) i de manera diferida (dos mesos després de la seva finalització) només al GP per constatar si s’han assolit els resultats previstos. Quan s’analitza l’evolució del GP s’observen millores en les habilitats d’autocontrol de les emocions, el reforç positiu i les relacions familiars. Tanmateix, des del punt de vista de les famílies no s’han observat canvis significatius en la millora de la percepció d’auto eficàcia del rol parental respecte el GC abans i després del programa. La percepció majoritària és que els objectius que planteja el programa són excessivament ambiciosos i en conseqüència, difícilment assolibles. Els responsables consideren que, en alguns casos, el perfil de famílies derivades al programa no és el més adequat perquè presenten problemàtiques molt més agudes a les desitjables per aquest tipus d’intervenció. Com a punts forts, es destaca que el programa és útil als ulls dels responsables i tècnics perquè genera una presa de consciència del problema i de la necessitat de canvi per part de les famílies. Els participants diuen transferir a la vida real algunes habilitats apreses especialment la comunicació i millora de les relacions familiars. Els tècnics aplicadors coincideixen amb la percepció de les famílies tot i declarar percentatges lleugerament inferiors. També és vist com un complement professional a la seva tasca que ajuda a fer un millor seguiment dels casos, i permet seguir treballant amb posterioritat amb les famílies.

Investigación evaluativa sobre el programa "LÍMITES"

Desde la comunidad científica se ha puesto de manifiesto la necesidad de evaluar los programas de intervención para la mejora de la parentalidad, especialmente en el contexto de la infancia y la adolescencia en riesgo. En esta investigación se presentan los resultados de la evaluación del programa Límites aportando evidencias de eficacia y efectividad, que permiten identificar y describir sus fortalezas, así como también aquellos elementos que pueden ser objeto de mejora. El programa Límites es una propuesta estructurada de intervención preventiva de carácter selectivo, con grupos de familias de jóvenes de entre 14 y 18 años que pasan por el circuito de la justicia juvenil. El programa ha estado funcionando desde 2007 en todo el territorio catalán, y ha incidido en un total de 351 personas y 245 familias. El programa consta de ocho sesiones en grupo en las que se trabajan contenidos relacionados con las relaciones y los vínculos, la comunicación, los conflictos, el establecimiento de normas y la disciplina. Para llevar a cabo la evaluación del programa Límites se ha partido de un diseño cuasi-experimental, pretest-postest aplicado a un grupo programa (GP) y grupo colaborador (GC) y de manera diferida (dos meses después de su finalización) sólo en el GP, para constatar si se han alcanzado los resultados previstos. Cuando se analiza la evolución del GP se observan mejoras en las habilidades de autocontrol de las emociones, el refuerzo positivo y las relaciones familiares. Sin embargo, desde el punto de vista de las familias no se han observado cambios significativos en la mejora de la percepción de auto eficacia del rol parental respecto al GC antes y después del programa. La percepción mayoritaria es que los objetivos que plantea el programa son excesivamente ambiciosos y en consecuencia, difícilmente alcanzables. Los responsables consideran que, en algunos casos, el perfil de familias derivadas al programa no es el más adecuado puesto que presenten problemáticas mucho más agudas a las deseables para este tipo de intervención. Como puntos fuertes, se destaca que el programa es útil a los ojos de los responsables y técnicos porque genera una toma de conciencia del problema y de la necesidad de cambio por parte de las familias. Los participantes dicen transferir a la vida real algunas habilidades aprendidas, especialmente la comunicación y mejora de las relaciones familiares. Los técnicos aplicadores coinciden con la percepción de las familias, a pesar de declarar porcentajes ligeramente inferiores. También es visto como un complemento profesional a su tarea que ayuda a hacer un mejor seguimiento de los casos, y permite seguir trabajando con posterioridad con las familias.