High frequency of CHD7 mutations in congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of normal pubertal development due to deficient gonadotropin-releasing hormone (GnRH) secretion or action, and is caused by genetic defects in several genes. Mutations in the CHD7 gene cause CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear abnormalities), but have also been found in patients with isolated CHH. The aim of this study was to identify CHD7 mutations in patients with CHH. Fifty Portuguese patients with CHH were screened for mutations in the CHD7 gene by DNA sequencing. Eight (16%) patients had CHD7 rare sequence variants that consisted of six missense (p.Gly388Glu, p.His903Pro, p.Thr1082Ile, p.Val1452Leu, p.Asp1854Gly, and p.Arg2065His) and two synonymous (p.Ser559Ser, and p.Ala2785Ala) mutations. Five of these mutations have never been reported before. Three CHD7 mutations occurred in patients that had mutations in additional CHH-genes. This study uncovered novel genetic variants that expand the known spectrum of mutations associated with CHH. The frequency of CHD7 mutations in this cohort was higher than that of other major CHH-genes and confirms the importance of including CHD7 in the genetic testing of CHH, even in the absence of additional CHARGE features.info:eu-repo/semantics/publishedVersio

A genome-wide association scan implicates <i>DCHS2, RUNX2, GLI3, PAX1</i> and <i>EDAR</i> in human facial variation

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar function

Differences in Spontaneously Avoiding or Approaching Mice Reflect Differences in CB1-Mediated Signaling of Dorsal Striatal Transmission

Approach or avoidance behaviors are accompanied by perceptual vigilance for, affective reactivity to and behavioral predisposition towards rewarding or punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice that responded with avoiding, balancing or approaching behaviors not induced by any experimental manipulation but spontaneously displayed in an approach/avoidance conflict task. Although the detailed neuronal mechanisms underlying the balancing between approach and avoidance are not fully clarified, there is growing evidence that endocannabinoid system (ECS) plays a critical role in the control of these balancing actions. The sensitivity of dorsal striatal synapses to the activation of cannabinoid CB1 receptors was investigated in the subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding animals displayed decreased control of CB1 receptors on GABAergic striatal transmission and in parallel increase of behavioral inhibition. Conversely, approaching animals exhibited increased control of CB1 receptors and in parallel increase of explorative behavior. Balancing animals reacted with balanced responses between approach and avoidance patterns. Treating avoiding animals with URB597 (fatty acid amide hydrolase inhibitor) or approaching animals with AM251 (CB1 receptor inverse agonist) reverted their respective behavioral and electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated control on dorsal striatal transmission represents the synaptic hallmark of the approach or avoidance behavior, respectively. Thus, the opposite spontaneous responses to conflicting stimuli are modulated by a different involvement of endocannabinoid signaling of dorsal striatal neurons in the range of temperamental traits related to individual differences

Sexual dimorphism in cranial morphology among modern South Africans

Pattern expressions of morphoscopic cranial traits vary across populations with classification accuracies being highly dependent on the reference collection to which unknown skulls are compared. Despite recent developments in populationspecific standards for South Africans, researchers have not addressed the accuracy of morphological methods. Several studies demonstrate differences in sexual dimorphism between South Africans and North Americans, warranting a need to re-evaluate sex estimation methods in South Africa. The purposes of this study were to test the reliability and accuracy of the Walker (2008) method and to examine patterns of sexual dimorphism among South Africans. A total of 245 modern Black and White South African male and female crania from the Pretoria Bone Collection, University of Pretoria, were scored using theWalker (2008) methodology. Cohen’s kappa was used to evaluate reliability of the method, and percent correct assessed validity of the method. Logistic regression was utilised to create modified population-specific formulae. Inter- and intra-observer agreement was moderate to excellent (0.60–0.90), except for the mental eminence (0.40). The percent correct results for sex were 80%or higher for combinations of glabella,mastoid andmenton and between 68 % and 73 % for menton, mastoid, orbital and nuchal margin using logistic equations of Walker (2008). White males had the highest (94–97 %) and White females had the lowest (31–62 %) percent correct. The low accuracies obtained when using Walker’s (2008) equations emphasised the need for population-specific sex estimation models. Modified formulae for South Africans were created, yielding higher classification rates (84–93 %) than when North American standards were employed.National Research Foundation (NRF)http://link.springer.com/journal/4142016-07-31hb201

The Organizational Vehicles of Islamic Political Dissent: Social Bases, Genealogies and Strategies

The organizational vehicles of Islamic political dissent vary greatly in the contemporary world. At one end of the spectrum, there could be full-fledged political parties occupying recognized positions in the official sphere of political life, and recently some of these have even come to take power in their respective countries. At the other end, however, one might find terrorist activity centred on small and isolated cells. Located somewhere in between could be a hos of mass organizations associated with religious social movements, peaceful or otherwise and in some cases, assorted militias that deal in intimidation or violence. These diverse vehicles have found different levels of success in specific contexts. It is shown here that what kinds of vehicles become predominant is largely contingent on how social alliances come to be built to represent the interests of an increasingly diverse ummah — the community of believers — in modern and profane competition over power and resources