Object Affordances Tune Observers' Prior Expectations about Tool-Use Behaviors

Learning about the function and use of tools through observation requires the ability to exploit one's own knowledge derived from past experience. It also depends on the detection of low-level local cues that are rooted in the tool's perceptual properties. Best known as ‘affordances’, these cues generate biomechanical priors that constrain the number of possible motor acts that are likely to be performed on tools. The contribution of these biomechanical priors to the learning of tool-use behaviors is well supported. However, it is not yet clear if, and how, affordances interact with higher-order expectations that are generated from past experience – i.e. probabilistic exposure – to enable observational learning of tool use. To address this question we designed an action observation task in which participants were required to infer, under various conditions of visual uncertainty, the intentions of a demonstrator performing tool-use behaviors. Both the probability of observing the demonstrator achieving a particular tool function and the biomechanical optimality of the observed movement were varied. We demonstrate that biomechanical priors modulate the extent to which participants' predictions are influenced by probabilistically-induced prior expectations. Biomechanical and probabilistic priors have a cumulative effect when they ‘converge’ (in the case of a probabilistic bias assigned to optimal behaviors), or a mutually inhibitory effect when they actively ‘diverge’ (in the case of probabilistic bias assigned to suboptimal behaviors)

Transformation-induced changes in the DNA-nuclear matrix interface, revealed by high-throughput analysis of DNA halos

In higher eukaryotic nuclei, DNA is periodically anchored to an extraction-resistant protein structure, via matrix attachment regions. We describe a refined and accessible method to non-subjectively, rapidly and reproducibly measure both size and stability of the intervening chromatin loops, and use it to demonstrate that malignant transformation compromises the DNA-nuclear matrix interface

Collision activity during training increases total energy expenditure measured via doubly labelled water

Purpose: Collision sports are characterised by frequent high intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. Methods: Using a randomised crossover design, six professional young male rugby league players completed two different five-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly seven days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. Results: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ±0.07; p=0.0021) total energy expenditure across the five-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ±0.74; p=0.007) session rating of perceived exertion and a very likely greater (-14.6 ± 3.3%; ES = -1.60 ±0.51; p=0.002) decrease in wellbeing 24h later. Conclusions: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused” alongside the kinematic “work required”. Key words: Nutrition, Recovery, Contact, Rugb

Immunocytochemical characterisation of cultures of human bladder mucosal cells

<p>Abstract</p> <p>Background</p> <p>The functional role of the bladder urothelium has been the focus of much recent research. The bladder mucosa contains two significant cell types: urothelial cells that line the bladder lumen and suburothelial interstitial cells or myofibroblasts. The aims of this study were to culture these cell populations from human bladder biopsies and to perform immunocytochemical characterisation.</p> <p>Methods</p> <p>Primary cell cultures were established from human bladder biopsies (n = 10). Individual populations of urothelial and myofibroblast-like cells were isolated using magnetic activated cell separation (MACS). Cells were slow growing, needing 3 to 5 weeks to attain confluence.</p> <p>Results</p> <p>Cytokeratin 20 positive cells (umbrella cells) were isolated at primary culture and also from patients' bladder washings but these did not proliferate. In primary culture, proliferating cells demonstrated positive immunocytochemical staining to cytokeratin markers (AE1/AE3 and A0575) as well fibroblasts (5B5) and smooth muscle (αSMA) markers. An unexpected finding was that populations of presumptive urothelial and myofibroblast-like cells, isolated using the MACS beads, stained for similar markers. In contrast, staining for cytokeratins and fibroblast or smooth muscle markers was not co-localised in full thickness bladder sections.</p> <p>Conclusions</p> <p>Our results suggest that, in culture, bladder mucosal cells may undergo differentiation into a myoepithelial cell phenotype indicating that urothelial cells have the capacity to respond to environmental changes. This may be important pathologically but also suggests that studies of the physiological function of these cells in culture may not give a reliable indicator of human physiology.</p

Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

SummaryGlobal dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.</jats:p

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

Male Mating Competitiveness of a Wolbachia-Introgressed Aedes polynesiensis Strain under Semi-Field Conditions

Aedes polynesiensis is the primary mosquito vector of lymphatic filariasis (LF) in the island nations of the South Pacific. Control of LF in this region of the world is difficult due to the unique biology of the mosquito vector. A proposed method to control LF in the Pacific is through the release of male mosquitoes that are effectively sterile. In order for this approach to be successful, it is critical that the modified male mosquitoes be able to compete with wild type male mosquitoes for female mates. In this study the authors examined the mating competitiveness of modified males under semi-field conditions. Modified males were released into field cages holding field-collected, virgin females and field collected wild type males. The resulting proportion of eggs that hatched was inversely related to the number of modified males released into the cage, which is consistent with the hypothesized competitiveness of modified males against indigenous males. The outcome indicates that mass release of modified A. polynesiensis mosquitoes could result in the suppression of A. polynesiensis populations and supports the continued development of applied strategies for suppression of this important disease vector

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Genome-Wide Association Study Identified a Narrow Chromosome 1 Region Associated with Chicken Growth Traits

Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS), we identified a narrow 1.5 Mb region (173.5–175 Mb) of chicken (Gallus gallus) chromosome (GGA) 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW) at 0–90 d of age measured weekly, biweekly average daily gains (ADG) derived from weekly body weight, and breast muscle weight (BMW), leg muscle weight (LMW) and wing weight (WW) at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22–48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29–42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA) of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22–42 d