Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers and X-Y Recombination.

Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/or occasional X-Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (∼5 Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X-Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleterious mutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosome.

Interleukin-22 is increased in multiple sclerosis patients and targets astrocytes.

BACKGROUND: Increasing evidences link T helper 17 (Th17) cells with multiple sclerosis (MS). In this context, interleukin-22 (IL-22), a Th17-linked cytokine, has been implicated in blood brain barrier breakdown and lymphocyte infiltration. Furthermore, polymorphism between MS patients and controls has been recently described in the gene coding for IL-22 binding protein (IL-22BP). Here, we aimed to better characterize IL-22 in the context of MS. METHODS: IL-22 and IL-22BP expressions were assessed by ELISA and qPCR in the following compartments of MS patients and control subjects: (1) the serum, (2) the cerebrospinal fluid, and (3) immune cells of peripheral blood. Identification of the IL-22 receptor subunit, IL-22R1, was performed by immunohistochemistry and immunofluorescence in human brain tissues and human primary astrocytes. The role of IL-22 on human primary astrocytes was evaluated using 7-AAD and annexin V, markers of cell viability and apoptosis, respectively. RESULTS: In a cohort of 141 MS patients and healthy control (HC) subjects, we found that serum levels of IL-22 were significantly higher in relapsing MS patients than in HC but also remitting and progressive MS patients. Monocytes and monocyte-derived dendritic cells contained an enhanced expression of mRNA coding for IL-22BP as compared to HC. Using immunohistochemistry and confocal microscopy, we found that IL-22 and its receptor were detected on astrocytes of brain tissues from both control subjects and MS patients, although in the latter, the expression was higher around blood vessels and in MS plaques. Cytometry-based functional assays revealed that addition of IL-22 improved the survival of human primary astrocytes. Furthermore, tumor necrosis factor α-treated astrocytes had a better long-term survival capacity upon IL-22 co-treatment. This protective effect of IL-22 seemed to be conferred, at least partially, by a decreased apoptosis. CONCLUSIONS: We show that (1) there is a dysregulation in the expression of IL-22 and its antagonist, IL-22BP, in MS patients, (2) IL-22 targets specifically astrocytes in the human brain, and (3) this cytokine confers an increased survival of the latter cells.

Lidar measurement of surface melt for a temperate Alpine glacier at the seasonal and hourly scales

This study shows how a new generation of terrestrial laser scanners can be used to investigate glacier surface ablation and other elements of glacial hydrodynamics at exceptionally high spatial and temporal resolution. The study area is an Alpine valley glacier, Haut Glacier d'Arolla, Switzerland. Here we use an ultra-long-range lidar RIEGL VZ-6000 scanner, having a laser specifically designed for measurement of snow- and ice-cover surfaces. We focus on two timescales: seasonal and daily. Our results show that a near-infrared scanning laser system can provide high-precision elevation change and ablation data from long ranges, and over relatively large sections of the glacier surface. We use it to quantify spatial variations in the patterns of surface melt at the seasonal scale, as controlled by both aspect and differential debris cover. At the daily scale, we quantify the effects of ogive-related differences in ice surface debris content on spatial patterns of ablation. Daily scale measurements point to possible hydraulic jacking of the glacier associated with short-term water pressure rises. This latter demonstration shows that this type of lidar may be used to address subglacial hydrologic questions, in addition to motion and ablation measurements.

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect methylated loci rather than a quantitative analysis. MethylCap-seq and HM450 data were dichotomized and performances were compared using a gold standard free Bayesian modelling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. In addition, genome-wide characteristics were compared, revealing that HM450 probes identified substantially fewer regions compared to MethylCap-seq. Although results indicated that the latter method can detect more potentially relevant DNA-methylation, this did not translate into the discovery of more differentially methylated loci between tumours and controls compared to HM450. Our results therefore indicate that both methodologies are complementary, with a higher sensitivity for HM450 and a far larger genome-wide coverage for MethylCap-seq, but also that a more comprehensive character does not automatically imply more significant results in biomarker studies.

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

OBJECTIVE: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. METHODS: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. RESULTS: 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. CONCLUSIONS: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.

Three Essays on International Trade and the Labor Market

The thesis is made of three independent chapters interested in the impact of globalization on workers in industrialized countries. The dissertation is especially focused on identifying the causal impact of international trade on workers' mobility, wages, and employment with both a short- and medium-term perspective. The first paper explores the relation between intra-industry trade (IIT) expansion and associated worker flows, taking the latter as an indicator of labor-market adjustment costs. Being the first study to combine theoretical simulations and a novel identification strategy, we find that both theoretical and empirical analyses are consistent with the "smooth adjustment hypothesis", according to which IIT expansion is less disruptive than inter-industry trade expansion. The study therefore lends support to the use of IIT indices as first-pass proxies for the adjustment effects of trade expansion. The second chapter contrasts the impact of increased import competition coming from China and the European Union (EU) on workers in the United Kingdom over a 15-year period. The most salient findings show that increased imports from China had significantly negative effects on workers' earnings, wages and employment. In contrast, larger imports from the EU are associated with positive worker-level outcomes, which is largely explained by the fact that increased imports from the EU were mostly offset by increased same-industry exports to the EU. Besides, we find that increased imports from China exert additional pressure on workers through spillovers to employment and wages in downstream industries. Finally, the last chapter is focused on the impact of exposure to trade and real exchange rate shocks on wages for Swiss manufacturing workers. A particular attention is made to consistently estimate the causal effect in using a two-step gravity-type identification strategy. The study shows that the impact of trade and exchange rate movements is concentrated among high-skilled workers almost exclusively.

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

BACKGROUND: Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. METHODS: The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. RESULTS: Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. LIMITATIONS: The use of cross-sectional data does not allow causal conclusions. CONCLUSIONS: This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care.

Conflict over multiple-partner mating between males and females of the polygynandrous common lizards.

The optimal number of mate partners for females rarely coincides with that for males, leading to a potential sexual conflict over multiple-partner mating. This suggests that the population sex ratio may affect multiple-partner mating and thus multiple paternity. We investigate the relationship between multiple paternity and the population sex ratio in the polygynandrous common lizard (Lacerta vivipara). In six populations the adult sex ratio was biased toward males, and in another six populations the adult sex ratio was biased toward females, the latter corresponding to the average adult sex ratio encountered in natural populations. In males the frequency and the degree of polygyny were lower in male-biased populations, as expected if competition among males determines polygyny. In females the frequency of polyandry was not different between treatments, and polyandrous females produced larger clutches, suggesting that polyandry might be adaptive. However, in male-biased populations females suffered from reduced reproductive success compared to female-biased populations, and the number of mate partners increased with female body size in polyandrous females. Polyandrous females of male-biased populations showed disproportionately more mating scars, indicating that polyandrous females of male-biased populations had more interactions with males and suggesting that the degree of multiple paternity is controlled by male sexual harassment. Our results thus imply that polyandry may be hierarchically controlled, with females controlling when to mate with multiple partners and male sexual harassment being a proximate determinant of the degree of multiple paternity. The results are also consistent with a sexual conflict in which male behaviors are harmful to females.

Elaborated Literary Violence: Genre and Ideology of the Two Stories I Sam 22,6-23 and II Sam 21,1-14

The present article focuses on two stories dealing with acts of big blood shed. I Sam 22,6-23 relates the massacre of the priests of Nob; II Sam 21,1-14 is about the execution of seven descendents of Saul, as atonement for Saul's attempt to exterminate the Gibeonites. Most researchers consider both stories or at least certain parts of them old.1 For both stories few verses are regarded as secondary. In this paper I try to reassess the analysis of these stories and will point to indices favoring a late date of origin for both of them. They concern the language in use, intertextual connections and particular motifs. A further indication consists in the fact that the reported events of the stories lack significant resonance in the corpus of the Hebrew Bible. There are only two texts, I Sam 2,33 and Ps 52,2, which allude or refer to I Sam 22,6-23.With regard to the importance of the related events and acts this silence in the Biblical context is astonishing. Interestingly, also in the Book of Chronicles one does not find any allusions to these stories. This raises the question whether the latter were composed after the formation of the book of Chronicles.

Reciprocal preening and food sharing in colour-polymorphic nestling barn owls.

Barn owl (Tyto alba) siblings preen and offer food items to one another, behaviours that can be considered prosocial because they benefit a conspecific by relieving distress or need. In experimental broods, we analysed whether such behaviours were reciprocated, preferentially exchanged between specific phenotypes, performed to avoid harassment and food theft or signals of hierarchy status. Three of the results are consistent with the hypothesis of direct reciprocity. First, food sharing was reciprocated in three-chick broods but not in pairs of siblings, that is when nestlings could choose a partner with whom to develop a reciprocating interaction. Second, a nestling was more likely to give a prey item to its sibling if the latter individual had preened the former. Third, siblings matched their investment in preening each other. Manipulation of age hierarchy showed that food stealing was directed towards older siblings but was not performed to compensate for a low level of cooperation received. Social behaviours were related to melanin-based coloration, suggesting that animals may signal their propensity to interact socially. The most prosocial phenotype (darker reddish) was also the phenotype that stole more food, and the effect of coloration on prosocial behaviour depended upon rank and sex, suggesting that colour-related prosociality is state dependent.

Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients.

Maladie des griffes du chat et autres bartonelloses [Cat scratch disease and other human infections caused by Bartonella species].

The different Bartonella species can cause various human infections such as cat scratch disease, chronic bacteremia (homeless patient with nonspecific symptom), endocarditis, bacillary angiomatosis, peliosis, and Carrion's disease. Diagnostic approaches include serology, culture and molecular approaches. PCR is especially useful on lymph nodes biopsies from patients with cat-scratch disease and on valvular samples taken from culture-negative endocarditis. Serology exhibits a very high sensitivity in the latter situation. The treatment should be chosen according to the clinical presentation.

A comparison of injuries among children and adult football (soccer) players

Football is a universal and an affordable game but we need to minimize the incidence of accidents among the increasing number of young football players. Our 11 year retrospective epidemiological study (1990-2000) of football injuries in children (N= 1000) was compared with those of adult players in the 2006 European Championship. This comparative study confirmed that the anatomical, biomechanical and biological conditions differ between adults and children and that they warrant particular attention to protect the latter vulnerable group against bone avulsions, overuse pathologies and fatigue-fractures. Injuries were shown to increase significantly with age up to 16 years (P=0.005). Children suffer mainly from contusions, fractures and sprain injuries. Head injuries were more common in boys (P=0.070), while girls were more prone to sprains. The types of injuries differ between adults and children (sprain versus fractures), the anatomical location of injuries is different (lower limbs in adults, lower and upper limbs in children), the circumstances of the injuries are different (contact in adults versus non-contact in children), and teenage girls have different types of injuries than teenage boys. An increased incidence of injuries is due to changes in the position of the center of gravity and in the morphotype during rapid growth. For these reasons it is mandatory to adapt the training to the age and sex of the players. It is unsafe to train children the same way as adults. The height, the weight and the speed of growth must be taken into account by the multidisciplinary team when organising the training programmes. -- Le football fait partie des sports les plus pratiqués au monde en raison de sa popularité et de son accessibilité économ ique. L'incidence des blessures liées à cette pratique doit être diminuée surtout chez les jeunes joueurs en raison de la croissance exponentielle du nombre de joueurs féminins et masculins. Une étude épidémiologique rétrospective sur 11 ans (1990-2000) a été réalisée chez les enfants victimes de blessures liées au football (N==1000), puis a été comparée aux données recueillies de l'UEFA lors d'un Championnat Européen en 2006 sur les lésions des joueurs adultes. Cette étude comparative confirme que les structures anatomiques, biologiques et les tensions biomécaniques chez l'enfant diffèrent de celles de l'adulte. Les enfants ont un risque plus élevé de souffrir d'avulsion osseuse et de fractures de fatigue que les adultes. Les blessures augmentent significativement avec l'âge jusqu'à 16 ans (P==0,005). Les traumatismes crâniens sont plus fréquents chez les garçons tandis que les entorses sont plus à risque chez les filles. Les adultes font plus souvent des entorses tandis que les enfants font plus de fractures. La localisation anatomique diffère également entre ces deux groupes (les membres inférieurs chez l'adulte et les membres inférieurs et supérieurs chez l'enfant). La circonstance des blessures diffère également (choc avec un autre joueur chez l'adulte et des blessures sans contact chez l'enfant). Chez les adolescents, les blessures des filles diffèrent de celles des garçons. L'augmentation chez les enfants de cette incidence est liée au déplacement lors de la croissance du centre de gravité, avec une maladresse accrue lors des phases de croissance. Pour toutes ces raisons, il est justifié d'adapter les entraînements de football en fonction de l'âge, du sexe et du morphotype. L'entrainement des enfants doit être différent de celui des adultes. Le poids, la taille et la vitesse de croissance doit être prise en compte dans des structures multidisciplinaires afin de permettre une meilleure longévité sportive des jeunes joueurs de football.

The cutting of cocaine and heroin: a critical review

The illicit drug cutting represents a complex problem that requires the sharing of knowledge from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not well known by the forensic community. Thus, this review aims at deciphering the different aspects of cutting, by gathering information mainly from criminology and criminalistics. It tackles essentially specificities of cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and diluents), their evolution in time and space and the analytical methodology implemented by forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting may take place. Moreover, researches studying how much cutting occurs in the country of destination are analysed. Lastly, the reasons for cutting are addressed. According to the literature, adulterants are added during production of the illicit drug or at a relatively high level of its distribution chain (e.g. before the product arrives in the country of destination or just after its importation in the latter). Their addition seems hardly justified by the only desire to increase profits or to harm consumers' health. Instead, adulteration would be performed to enhance or to mimic the illicit drug effects or to facilitate administration of the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin are frequently detected in cocaine specimens, while paracetamol and caffeine are almost exclusively identified in heroin specimens. This may reveal differences in the respective structures of production and/or distribution of cocaine and heroin. As the relevant information about cutting is spread across different scientific fields, a close collaboration should be set up to collect essential and unified data to improve knowledge and provide information for monitoring, control and harm reduction purposes. More research, on several areas of investigation, should be carried out to gather relevant information.

Psychosocial Quality-of-Life, Lifestyle and Adiposity: A Longitudinal Study in Pre-schoolers (Ballabeina Study).

PURPOSE: In obesity prevention, understanding psychosocial influences in early life is pivotal. Reviews reported contradictory results and a lack of longitudinal studies focusing on underlying lifestyle factors. This study tested whether psychosocial Quality-Of-Life (QOL) was associated with pre-schoolers' lifestyle and adiposity changes over one school year and whether lifestyle moderated the latter. It was hypothesised that QOL might not impact adiposity in everybody but that this might depend on preceding lifestyle. METHOD: Longitudinal data from 291 Swiss pre-schoolers (initially 3.9-6.3 years) was available. The following measures were used in longitudinal regressions: psychosocial QOL by PedsQL, adiposity (BMI z-score, waist, fat%), diet (food frequency), sedentary time and accelerometer-based activity. RESULTS: Concerning lifestyle, low psychosocial QOL was only related to unfavourable changes in diet (less fruit β = 0.21 and more fat intake β = -0.28) and lower physical activity (β = 0.21). Longitudinal QOL-adiposity relations appeared only after moderation by lifestyle factors (beta-range 0.13-0.67). Low psychosocial QOL was associated with increased adiposity in children with an unhealthy diet intake or high sedentary time. By contrast, low psychosocial QOL was associated with decreasing adiposity in high fruit consumers or more physically active pre-schoolers. CONCLUSION: Results emphasise the need for testing moderation in the QOL-adiposity relation. An unhealthy diet can be a vulnerability factor and high physical activity a protective factor in QOL-related adiposity. Consequently, QOL and lifestyle should be targeted concurrently in multi-factorial obesity prevention. The environment should be an 'activity encouraging, healthy food zone' that minimises opportunities for stress-induced eating. In addition, appropriate stress coping skills should be acquired.