Effects of Visual Feedback-Induced Variability on Motor Learning of Handrim Wheelchair Propulsion

BackgroundIt has been suggested that a higher intra-individual variability benefits the motor learning of wheelchair propulsion. The present study evaluated whether feedback-induced variability on wheelchair propulsion technique variables would also enhance the motor learning process. Learning was operationalized as an improvement in mechanical efficiency and propulsion technique, which are thought to be closely related during the learning process.Methods17 Participants received visual feedback-based practice (feedback group) and 15 participants received regular practice (natural learning group). Both groups received equal practice dose of 80 min, over 3 weeks, at 0.24 W/kg at a treadmill speed of 1.11 m/s. To compare both groups the pre- and post-test were performed without feedback. The feedback group received real-time visual feedback on seven propulsion variables with instruction to manipulate the presented variable to achieve the highest possible variability (1^st 4-min block) and optimize it in the prescribed direction (2^nd 4-min block). To increase motor exploration the participants were unaware of the exact variable they received feedback on. Energy consumption and the propulsion technique variables with their respective coefficient of variation were calculated to evaluate the amount of intra-individual variability.ResultsThe feedback group, which practiced with higher intra-individual variability, improved the propulsion technique between pre- and post-test to the same extent as the natural learning group. Mechanical efficiency improved between pre- and post-test in the natural learning group but remained unchanged in the feedback group.ConclusionThese results suggest that feedback-induced variability inhibited the improvement in mechanical efficiency. Moreover, since both groups improved propulsion technique but only the natural learning group improved mechanical efficiency, it can be concluded that the improvement in mechanical efficiency and propulsion technique do not always appear simultaneously during the motor learning process. Their relationship is most likely modified by other factors such as the amount of the intra-individual variability.     

Analysis of the community structure of abyssal kinetoplastids revealed similar communities at larger spatial scales

Knowledge of the spatial scales of diversity is necessary to evaluate the mechanisms driving biodiversity and biogeography in the vast but poorly understood deep sea. The community structure of kinetoplastids, an important group of microbial eukaryotes belonging to the Euglenozoa, from all abyssal plains of the South Atlantic and two areas of the eastern Mediterranean was studied using partial small subunit ribosomal DNA gene clone libraries. A total of 1364 clones from 10 different regions were retrieved. The analysis revealed statistically not distinguishable communities from both the South-East Atlantic (Angola and Guinea Basin) and the South-West Atlantic (Angola and Brazil Basin) at spatial scales of 1000–3000 km, whereas all other communities were significantly differentiated from one another. It seems likely that multiple processes operate at the same time to shape communities of deep-sea kinetoplastids. Nevertheless, constant and homogenous environmental conditions over large spatial scales at abyssal depths, together with high dispersal capabilities of microbial eukaryotes, maintain best the results of statistically indistinguishable communities at larger spatial scales.     

Evidence That Calls-Based and Mobility Networks Are Isomorphic

Social relations involve both face-to-face interaction as well as telecommunications. We can observe the geography of phone calls and of the mobility of cell phones in space. These two phenomena can be described as networks of connections between different points in space. We use a dataset that includes billions of phone calls made in Colombia during a six-month period. We draw the two networks and find that the call-based network resembles a higher order aggregation of the mobility network and that both are isomorphic except for a higher spatial decay coefficient of the mobility network relative to the call-based network: when we discount distance effects on the call connections with the same decay observed for mobility connections, the two networks are virtually indistinguishable.     

The KNS1 gene of Saccharomyces cerevisiae encodes a nonessential protein kinase homologue that is distantly related to members of the CDC28/cdc2 gene family

Summary A novel protein kinase homologue (KNS1) has been identified in Saccharomyces cerevisiae. KNS1 contains an open reading frame of 720 codons. The carboxy-terminal portion of the predicted protein sequence is similar to that of many other protein kinases, exhibiting 36% identity to the cdc2 gene product of Schizosaccharomyces pombe and 34% identity to the CDC28 gene product of S. cerevisiae. Deletion mutations were constructed in the KNS1 gene. kns1 mutants grow at the same rate as wild-type cells using several different carbon sources. They mate at normal efficiencies, and they sporulate successfully. No defects were found in entry into or exit from stationary phase. Thus, the KNS1 gene is not essential for cell growth and a variety of other cellular processes in yeast.     

Discriminatory Role of Detergent-Resistant Membranes in the Dimerization and Endocytosis of Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer.     

Interaction with Tsg101 Is Necessary for the Efficient Transport and Release of Nucleocapsids in Marburg Virus-Infected Cells

Endosomal sorting complex required for transport (ESCRT) machinery supports the efficient budding of Marburg virus (MARV) and many other enveloped viruses. Interaction between components of the ESCRT machinery and viral proteins is predominantly mediated by short tetrapeptide motifs, known as late domains. MARV contains late domain motifs in the matrix protein VP40 and in the genome-encapsidating nucleoprotein (NP). The PSAP late domain motif of NP recruits the ESCRT-I protein tumor susceptibility gene 101 (Tsg101). Here, we generated a recombinant MARV encoding NP with a mutated PSAP late domain (rMARV_PSAPmut). rMARV_PSAPmut was attenuated by up to one log compared with recombinant wild-type MARV (rMARV_wt), formed smaller plaques and exhibited delayed virus release. Nucleocapsids in rMARV_PSAPmut-infected cells were more densely packed inside viral inclusions and more abundant in the cytoplasm than in rMARV_wt-infected cells. A similar phenotype was detected when MARV-infected cells were depleted of Tsg101. Live-cell imaging analyses revealed that Tsg101 accumulated in inclusions of rMARV_wt-infected cells and was co-transported together with nucleocapsids. In contrast, rMARV_PSAPmut nucleocapsids did not display co-localization with Tsg101, had significantly shorter transport trajectories, and migration close to the plasma membrane was severely impaired, resulting in reduced recruitment into filopodia, the major budding sites of MARV. We further show that the Tsg101 interacting protein IQGAP1, an actin cytoskeleton regulator, was recruited into inclusions and to individual nucleocapsids together with Tsg101. Moreover, IQGAP1 was detected in a contrail-like structure at the rear end of migrating nucleocapsids. Down regulation of IQGAP1 impaired release of MARV. These results indicate that the PSAP motif in NP, which enables binding to Tsg101, is important for the efficient actin-dependent transport of nucleocapsids to the sites of budding. Thus, the interaction between NP and Tsg101 supports several steps of MARV assembly before virus fission.     

Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy

Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.