Upper-limb kinematics and coordination of short grip and classic drives in field hockey

The aim of this study was to compare the upper-limb kinematics and coordination of the short grip and classic drives in field hockey. Ten elite female players participated in the experiment. The VICON system was used to record the displacement of markers placed on the stick and the players' joints during five short grip and five classic drives. Kinematic and coordination parameters were analyzed. The ball's velocity was recorded by a radar device that also served as the drive target. Kinematic differences were noted between the two drive conditions, with shorter duration and smaller overall amplitude in the short grip drive, explained by the shorter lever arm and the specific context in which it is used. No differences were noted for upper-limb coordination. In both types of stick holding, an interlimb dissociation was noted on the left side, whereas the right interlimb coordination was in phase. Moreover, the time lag increased in the disto-proximal direction, suggesting wrist uncocking before impact and the initiation of descent motion by the left shoulder. Mediolateral analysis confirmed these results: coordination of left-right limbs converged at the wrist but dissociated with more proximal joints (elbows and shoulders).     

p53-Independent Apoptosis and p53-Dependent Block of DNA Rereplication Following Mitotic Spindle Inhibition in Human Cells

We have studied the response of human transformed cells to mitotic spindle inhibition. Two paired cell lines, K562 and its parvovirus-resistant KS derivative clone, respectively nonexpressing and expressing p53, were continuously exposed to nocodazole. Apoptotic cells were observed in both lines, indicating that mitotic spindle impairment induced p53-independent apoptosis. After a transient mitotic delay, both cell lines exited mitosis, as revealed by flow-cytometric determination of MPM2 antigen and cyclin B1 expression, coupled to cytogenetic analysis of sister centromere separation. Both cell lines exited mitosis without chromatid segregation. K562 p53-deficient cells further resumed DNA synthesis, giving rise to cells with a DNA content above 4C, and reentered a polyploid cycle. In contrast, KS cells underwent a subsequent G1 arrest in the tetraploid state. Thus, G1 arrest in tetraploid cells requires p53 function in the rereplication checkpoint which prevents the G1/S transition following aberrant mitosis; in contrast, p53 expression is dispensable for triggering the apoptotic response in the absence of mitotic spindle.     

Phylogenetic and Functional Diversity of Microbial Communities Associated with Subsurface Sediments of the Sonora Margin,Guaymas Basin

Subsurface sediments of the Sonora Margin (Guaymas Basin), located in proximity of active cold seep sites were explored. The taxonomic and functional diversity of bacterial and archaeal communities were investigated from 1 to 10 meters below the seafloor. Microbial community structure and abundance and distribution of dominant populations were assessed using complementary molecular approaches (Ribosomal Intergenic Spacer Analysis, 16S rRNA libraries and quantitative PCR with an extensive primers set) and correlated to comprehensive geochemical data. Moreover the metabolic potentials and functional traits of the microbial community were also identified using the GeoChip functional gene microarray and metabolic rates. The active microbial community structure in the Sonora Margin sediments was related to deep subsurface ecosystems (Marine Benthic Groups B and D, Miscellaneous Crenarchaeotal Group, Chloroflexi and Candidate divisions) and remained relatively similar throughout the sediment section, despite defined biogeochemical gradients. However, relative abundances of bacterial and archaeal dominant lineages were significantly correlated with organic carbon quantity and origin. Consistently, metabolic pathways for the degradation and assimilation of this organic carbon as well as genetic potentials for the transformation of detrital organic matters, hydrocarbons and recalcitrant substrates were detected, suggesting that chemoorganotrophic microorganisms may dominate the microbial community of the Sonora Margin subsurface sediments.     

Label‐free characterization of carbonic anhydrase—novel inhibitor interactions using surface plasmon resonance,isothermal titration calorimetry and fluorescence‐based thermal shift assays

This work describes the development of biophysical unbiased methods to study the interactions between new designed compounds and carbonic anhydrase II (CAII) enzyme. These methods have to permit both a screening of a series of sulfonamide derivatives and the identification of a lead compound after a thorough study of the most promising molecules. Interactions data were collected using surface plasmon resonance (SPR) and thermal shift assay (TSA). In the first step, experiments were performed with bovine CAII isoform and were extended to human CAII. Isothermal titration calorimetry (ITC) experiments were also conducted to obtain thermodynamics parameters necessary for the processing of the TSA data. Results obtained with this reference methodology demonstrate the effectiveness of SPR and TSA. K_D values obtained from SPR data were in perfect accordance with ITC. For TSA, despite the fact that the absolute values of K_D were quite different, the same affinity scale was obtained for all compounds. The binding affinities of the analytes studied vary by more than 50 orders of magnitude; for example, the K_D value determined by SPR were 6 ± 4 and 299 ± 25 nM for compounds 1 and 3, respectively. This paper discusses some of the theoretical and experimental aspects of the affinity‐based methods and evaluates the protein consumption to develop methods for the screening of further new compounds. The double interest of SPR, that is, for screening and for the quick thorough study of the interactions parameters (k_a, k_d, and K_D), leads us to choose this methodology for the study of new potential inhibitors. Copyright © 2013 John Wiley & Sons, Ltd.     

Molecular characterization of a series of 990 index patients with albinism

Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype–genotype correlations. To obtain a precise diagnosis, we screened the 19 known albinism genes in 990 index patients using targeted next‐generation sequencing (NGS) and high‐resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total of 243 new pathogenic variants were identified. Intragenic rearrangements represented 10.8% of all pathogenic alleles. NGS panel analysis allowed establishing a diagnosis for the rarest forms of the disease, which could not be diagnosed otherwise. Because of the clinical overlap between the different forms of the disease, diagnosis nowadays clearly relies on molecular grounds.     

BAC end sequences corresponding to the B4 resistance gene cluster in common bean: a resource for markers and synteny analyses

In common bean, a complex disease resistance (R) gene cluster, harboring many specific R genes against various pathogens, is located at the end of the linkage group B4. A BAC library of the Meso-american bean genotype BAT93 was screened with PRLJ1, a probe previously shown to be specific to the B4 R gene cluster, leading to the identification of 73 positive BAC clones. BAC-end sequencing (BES) of the 73 positive BACs generated 75 kb of sequence. These BACs were organized into 6 contigs, all mapped at the B4 R gene cluster. To evaluate the potential of BES for marker development, BES-derived specific primers were used to check for linkage with two allelic anthracnose R specificities Co-3 and Co-3 ( 2 ), through the analysis of pairs of Near Isogenic Lines (NILs). Out of 32 primer pairs tested, two revealed polymorphisms between the NILs, confirming the suspected location of Co-3 and Co-3 ( 2 ) at the B4 cluster. In order to identify the orthologous region of the B4 R gene cluster in the two model legume genomes, bean BESs were used as queries in TBLASTX searches of Medicago truncatula and Lotus japonicus BAC clones. Putative orthologous regions were identified on chromosome Mt6 and Lj2, in agreement with the colinearity observed between Mt and Lj for these regions.     

Evaluation of species distribution models by resampling of sites surveyed a century ago by Joseph Grinnell

Species distribution models (SDMs) are commonly applied to predict species’ responses to anticipated global change, but lack of data from future time periods precludes assessment of their reliability. Instead, performance against test data in the same era is assumed to correlate with accuracy in the future. Moreover, high‐confidence absence data is required for testing model accuracy but is often unavailable since a species may be present when undetected. Here we evaluate the performance of eight SDMs trained with historic (1900–1939) or modern (1970–2009) climate data and occurrence records for 18 mammalian species. Models were projected to the same or the opposing time period and evaluated with data obtained from surveys conducted by Joseph Grinnell and his colleagues in the Sierra Nevada of California from 1900 to 1939 and modern resurveys from 2003 to 2011. Occupancy modeling was used to confidently assign absences at test sites where species were undetected. SDMs were evaluated using species’ presences combined with this high‐confidence absence (HCA) set, a low‐confidence set in which non‐detections were assumed to indicate absence (LCA), and randomly located ‘pseudoabsences’ (PSA). Model performance increased significantly with the quality of absences (mean AUC ± SE: 0.76 ± 0.01 for PSA, 0.79 ± 0.01 for LCA, and 0.81 ± 0.01 for HCA), and apparent differences between SDMs declined as the quality of test absences increased. Models projecting across time performed as well as when projecting within the same time period when assessed with threshold‐independent metrics. However, accuracy of presence and absence predictions sometimes declined in cross‐era projections. Although most variation in performance occurred among species, autecological traits were only weakly correlated with model accuracy. Our study indicates that a) the quality of evaluation data affects assessments of model performance; b) within‐era performance correlates positively but unreliably with cross‐era performance; and c) SDMs can be reliably but cautiously projected across time.     

Novel variants in the BLOC1S3 gene in patients presenting a mild form of Hermansky–Pudlak syndrome

Hermansky–Pudlak syndrome (HPS) associates oculocutaneous albinism and systemic affections including platelet dense granules anomalies leading to bleeding diathesis and, depending on the form, pulmonary fibrosis, immunodeficiency, and/or granulomatous colitis. So far, 11 forms of autosomal recessive HPS caused by pathogenic variants in 11 different genes have been reported. We describe three HPS‐8 consanguineous families with different homozygous pathogenic variants in BLOC1S3 (NM_212550.3), one of which is novel. These comprise two deletions leading to a reading frameshift (c.385_403del, c.338_341del) and one in frame deletion (c.444_467del). All patients have moderate oculocutaneous albinism and bleeding diathesis, but other HPS symptoms are not described. One patient diagnosed with HPS‐8 suffered from lymphocyte‐predominant Hodgkin lymphoma. The mild severity of HPS‐8 is consistent with other HPS forms caused by variants in BLOC‐1 complex coding genes (HPS‐7, DTNBP1; HPS‐9, BLOC1S6, HPS‐11, BLOC1S5).     

Comparative in vitro activity of chlorine and bromine on the cysts of free-living amoebae

A continuous flow type apparatus is used for investigation of the chlorine and bromide activity in vitro on the cysts of two free-living amoeba strains : Naegleria gruberi and Acanthamoeba polyphaga. The Naegleria cysts are sensitive more to chlorine than to bromine ; those of Acanthamoeba are perfectly resistant to these disinfectants in the limit of the available concentrations in swimming-pools. The sensibility to these disinfectants stays the same at 25 degrees C and 35 degrees C.