Social chromosome variants differentially affect queen determination and the survival of workers in the fire ant Solenopsis invicta.

Intraspecific variation in social organization is common, yet the underlying causes are rarely known. An exception is the fire ant Solenopsis invicta in which the existence of two distinct forms of social colony organization is under the control of the two variants of a pair of social chromosomes, SB and Sb. Colonies containing exclusively SB/SB workers accept only one single queen and she must be SB/SB. By contrast, when colonies contain more than 10% of SB/Sb workers, they accept several queens but only SB/Sb queens. The variants of the social chromosome are associated with several additional important phenotypic differences, including the size, fecundity and dispersal strategies of queens, aggressiveness of workers, and sperm count in males. However, little is known about whether social chromosome variants affect fitness in other life stages. Here, we perform experiments to determine whether differential selection occurs during development and in adult workers. We find evidence that the Sb variant of the social chromosome increases the likelihood of female brood to develop into queens and that adult SB/Sb workers, the workers that cull SB/SB queens, are overrepresented in comparison to SB/SB workers. This demonstrates that supergenes such as the social chromosome can have complex effects on phenotypes at various stages of development.

Physiotherapy practice in the private sector: organizational characteristics and models.

BACKGROUND: Even if a large proportion of physiotherapists work in the private sector worldwide, very little is known of the organizations within which they practice. Such knowledge is important to help understand contexts of practice and how they influence the quality of services and patient outcomes. The purpose of this study was to: 1) describe characteristics of organizations where physiotherapists practice in the private sector, and 2) explore the existence of a taxonomy of organizational models. METHODS: This was a cross-sectional quantitative survey of 236 randomly-selected physiotherapists. Participants completed a purpose-designed questionnaire online or by telephone, covering organizational vision, resources, structures and practices. Organizational characteristics were analyzed descriptively, while organizational models were identified by multiple correspondence analyses. RESULTS: Most organizations were for-profit (93.2%), located in urban areas (91.5%), and within buildings containing multiple businesses/organizations (76.7%). The majority included multiple providers (89.8%) from diverse professions, mainly physiotherapy assistants (68.7%), massage therapists (67.3%) and osteopaths (50.2%). Four organizational models were identified: 1) solo practice, 2) middle-scale multiprovider, 3) large-scale multiprovider and 4) mixed. CONCLUSIONS: The results of this study provide a detailed description of the organizations where physiotherapists practice, and highlight the importance of human resources in differentiating organizational models. Further research examining the influences of these organizational characteristics and models on outcomes such as physiotherapists' professional practices and patient outcomes are needed.

Population demography and the evolution of helping behaviors.

Limited dispersal may favor the evolution of helping behaviors between relatives as it increases their relatedness, and it may inhibit such evolution as it increases local competition between these relatives. Here, we explore one way out of this dilemma: if the helping behavior allows groups to expand in size, then the kin-competition pressure opposing its evolution can be greatly reduced. We explore the effects of two kinds of stochasticity allowing for such deme expansion. First, we study the evolution of helping under environmental stochasticity that may induce complete patch extinction. Helping evolves if it results in a decrease in the probability of extinction or if it enhances the rate of patch recolonization through propagules formed by fission of nonextinct groups. This mode of dispersal is indeed commonly found in social species. Second, we consider the evolution of helping in the presence of demographic stochasticity. When fecundity is below its value maximizing deme size (undersaturation), helping evolves, but under stringent conditions unless positive density dependence (Allee effect) interferes with demographic stochasticity. When fecundity is above its value maximizing deme size (oversaturation), helping may also evolve, but only if it reduces negative density-dependent competition.

Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine.

Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.

Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1.

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

Behind the Scenes of an Ant Genome Project

Dramatic improvements in DNA sequencing technologies have led to amore than 1,000-fold reduction in sequencing costs over the past five years.Genome-wide research approaches can thus now be applied beyond medicallyrelevant questions to examine the molecular-genetic basis of behavior,development and unique life histories in almost any organism. A first step foran emerging model organism is usually establishing a reference genomesequence. I offer insight gained from the fire ant genome project. First, I detailhow the project came to be and how sequencing, assembly and annotationstrategies were chosen. Subsequently, I describe some of the issues linked toworking with data from recently sequenced genomes. Finally, I discuss anapproach undertaken in a follow-up project based on the fire ant genomesequence.

Segmentation and Clustering of Textual Sequences: a Typological Approach

The long term goal of this research is to develop a program able to produce an automatic segmentation and categorization of textual sequences into discourse types. In this preliminary contribution, we present the construction of an algorithm which takes a segmented text as input and attempts to produce a categorization of sequences, such as narrative, argumentative, descriptive and so on. Also, this work aims at investigating a possible convergence between the typological approach developed in particular in the field of text and discourse analysis in French by Adam (2008) and Bronckart (1997) and unsupervised statistical learning.

Proximity-dependent pollen performance in Silene vulgaris.

BACKGROUND AND AIMS: Pollen and seed dispersal in herbaceous insect-pollinated plants are often restricted, inducing strong population structure. To what extent this influences mating within and among patches is poorly understood. This study investigates the influence of population structure on pollen performance using controlled pollinations and genetic markers. METHODS: Population structure was investigated in a patchily distributed population of gynodioecious Silene vulgaris in Switzerland using polymorphic microsatellite markers. Experimental pollinations were performed on 21 hermaphrodite recipients using pollen donors at three spatial scales: (a) self-pollination; (b) within-patch cross-pollinations; and (c) between-patch cross-pollinations. Pollen performance was then compared with respect to crossing distance. KEY RESULTS: The population of S. vulgaris was characterized by a high degree of genetic sub-structure, with neighbouring plants more related to one another than to distant individuals. Inbreeding probably results from both selfing and biparental inbreeding. Pollen performance increased with distance between mates. Between-patch pollen performed significantly better than both self- and within-patch pollen donors. However, no significant difference was detected between self- and within-patch pollen donors. CONCLUSIONS: The results suggest that population structure in animal-pollinated plants is likely to influence mating patterns by favouring cross-pollinations between unrelated plants. However, the extent to which this mechanism could be effective as a pre-zygotic barrier preventing inbred mating depends on the patterns of pollinator foraging and their influence on pollen dispersal.

A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies.

BACKGROUND: CD19 is a B cell lineage specific surface receptor whose broad expression, from pro-B cells to early plasma cells, makes it an attractive target for the immunotherapy of B cell malignancies. In this study we present the generation of a novel humanized anti-CD19 monoclonal antibody (mAb), GBR 401, and investigate its therapeutic potential on human B cell malignancies. METHODS: GBR 401 was partially defucosylated in order to enhance its cytotoxic function. We analyzed the in vitro depleting effects of GBR 401 against B cell lines and primary malignant B cells from patients in the presence or in absence of purified NK cells isolated from healthy donors. In vivo, the antibody dependent cellular cytotoxicity (ADCC) efficacy of GBR 401 was assessed in a B cell depletion model consisting of SCID mice injected with healthy human donor PBMC, and a malignant B cell depletion model where SCID mice are xenografted with both primary human B-CLL tumors and heterologous human NK cells. Furthermore, the anti-tumor activity of GBR 401 was also evaluated in a xenochimeric mouse model of human Burkitt lymphoma using mice xenografted intravenously with Raji cells. Pharmacological inhibition tests were used to characterize the mechanism of the cell death induced by GBR 401. RESULTS: GBR 401 exerts a potent in vitro and in vivo cytotoxic activity against primary samples from patients representing various B-cell malignancies. GBR 401 elicits a markedly higher level of ADCC on primary malignant B cells when compared to fucosylated similar mAb and to Rituximab, the current anti-CD20 mAb standard immunotherapeutic treatment for B cell malignancies, showing killing at 500 times lower concentrations. Of interest, GBR 401 also exhibits a potent direct killing effect in different malignant B cell lines that involves homotypic aggregation mediated by actin relocalization. CONCLUSION: These results contribute to consolidate clinical interest in developing GBR 401 for treatment of hematopoietic B cell malignancies, particularly for patients refractory to anti-CD20 mAb therapies.

Substance use among sportive adolescents in the French-speaking part of Switzerland

[Contents] Introduction. Objectives. Methodology. Results. Characteristics of the sample. Substance use (Psychoactive substances, Performance-enhancing substances). Profile of sportive adolescents using substances. Mixed substance use. Other factors related to substance use. Inactivity. Conclusions. References. Annexes. Annex 1. Questionnaire. Annex 2. Sample weighting procedure. Annex 3. Sports type.