Visual Performance Fields: Frames of Reference

Performance in most visual discrimination tasks is better along the horizontal than the vertical meridian (Horizontal-Vertical Anisotropy, HVA), and along the lower than the upper vertical meridian (Vertical Meridian Asymmetry, VMA), with intermediate performance at intercardinal locations. As these inhomogeneities are prevalent throughout visual tasks, it is important to understand the perceptual consequences of dissociating spatial reference frames. In all studies of performance fields so far, allocentric environmental references and egocentric observer reference frames were aligned. Here we quantified the effects of manipulating head-centric and retinotopic coordinates on the shape of visual performance fields. When observers viewed briefly presented radial arrays of Gabors and discriminated the tilt of a target relative to homogeneously oriented distractors, performance fields shifted with head tilt (Experiment 1), and fixation (Experiment 2). These results show that performance fields shift in-line with egocentric referents, corresponding to the retinal location of the stimulus

Modeling of B cell Synapse Formation by Monte Carlo Simulation Shows That Directed Transport of Receptor Molecules Is a Potential Formation Mechanism

The formation of the protein segregation structure known as the “immunological synapse” in the contact region between B cells and antigen presenting cells appears to precede antigen (Ag) uptake by B cells. The mature B cell synapse consists of a central cluster of B cell receptor/Antigen (BCR/Ag) complexes surrounded by a ring of LFA-1/ICAM-1 complexes. In this study, we used an in silico model to investigate whether cytoskeletally driven transport of molecules toward the center of the contact zone is a potential mechanism of immunological synapse formation in B cells. We modeled directed transport by the cytoskeleton in an effective manner, by biasing the diffusion of molecules toward the center of the contact zone. Our results clearly show that biased diffusion of BCR/Ag complexes on the B cell surface is sufficient to produce patterns similar to experimentally observed immunological synapses. This is true even in the presence of significant membrane deformation as a result of receptor–ligand binding, which in previous work we showed had a detrimental effect on synapse formation at high antigen affinity values. Comparison of our model’s results to those of experiments shows that our model produces synapses for realistic length, time, and affinity scales. Our results also show that strong biased diffusion of free molecules has a negative effect on synapse formation by excluding BCR/Ag complexes from the center of the contact zone. However, synapses may still form provided the bias in diffusion of free molecules is an order-of-magnitude weaker than that of BCR/Ag complexes. We also show how diffusion trajectories obtained from single-molecule tracking experiments can generate insight into the mechanism of synapse formation

Impact of the Covid-19 pandemic on perinatal mental health (Riseup-PPD-COVID-19): protocol for an international prospective cohort study

Background: Corona Virus Disease 19 (COVID-19) is a new pandemic, declared a public health emergency by the World Health Organization, which could have negative consequences for pregnant and postpartum women. The scarce evidence published to date suggests that perinatal mental health has deteriorated since the COVID-19 outbreak. However, the few studies published so far have some limitations, such as a cross-sectional design and the omission of important factors for the understanding of perinatal mental health, including governmental restriction measures and healthcare practices implemented at the maternity hospitals. Within the Riseup-PPD COST Action, a study is underway to assess the impact of COVID-19 in perinatal mental health. The primary objectives are to (1) evaluate changes in perinatal mental health outcomes; and (2) determine the risk and protective factors for perinatal mental health during the COVID-19 pandemic. Additionally, we will compare the results between the countries participating in the study. Methods: This is an international prospective cohort study, with a baseline and three follow-up assessments over a six-month period. It is being carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom), Argentina, Brazil and Chile. The sample consists of adult pregnant and postpartum women (with infants up to 6 months of age). The assessment includes measures on COVID-19 epidemiology and public health measures (Oxford COVID-19 Government Response Tracker dataset), Coronavirus Perinatal Experiences (COPE questionnaires), psychological distress (BSI-18), depression (EPDS), anxiety (GAD-7) and post-traumatic stress symptoms (PTSD checklist for DSM-V). Discussion: This study will provide important information for understanding the impact of the COVID-19 pandemic on perinatal mental health and well-being, including the identification of potential risk and protective factors by implementing predictive models using machine learning techniques. The findings will help policymakers develop suitable guidelines and prevention strategies for perinatal mental health and contribute to designing tailored mental health interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04595123.The project is part of the COST Action Riseup-PPD CA 18138 and was supported by COST under COST Action Riseup-PPD CA18138; also, by the Spanish Ministry of Health, the Institute of Health Carlos III, and the European Regional Development Fund «Una manera de hacer Europa» by the Prevention and Health Promotion Research Network ‘redIAPP’ (RD16/0007). Raquel Costa is supported by the FSE and FCT under an individual Post-Doctoral Grant SFRH/BPD/117597/2016. Rena Bina and Drorit Levy received funding from the Bar-Ilan Dangoor Centre for Personalized Medicine, Israel. Ana Mesquita is supported from the Portuguese Foundation for Science and Technology (FCT) and from EU through the European Social Fund and from the Human Potential Operational Program - IF/00750/2015. Ana Osório received financial support from CAPES/Proex no. 0653/2018 and CAPES/PrInt grant no. 88887.310343/2018-00.The funders of the study had no role in the study design or the writing the protocol. The corresponding author had final responsibility for the decision to submit for publication

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Monte Carlo vs. Pencil Beam based optimization of stereotactic lung IMRT

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study is to compare finite size pencil beam (fsPB) and Monte Carlo (MC) based optimization of lung intensity-modulated stereotactic radiotherapy (lung IMSRT).</p> <p>Materials and methods</p> <p>A fsPB and a MC algorithm as implemented in a biological IMRT planning system were validated by film measurements in a static lung phantom. Then, they were applied for static lung IMSRT planning based on three different geometrical patient models (one phase static CT, density overwrite one phase static CT, average CT) of the same patient. Both 6 and 15 MV beam energies were used. The resulting treatment plans were compared by how well they fulfilled the prescribed optimization constraints both for the dose distributions calculated on the static patient models and for the accumulated dose, recalculated with MC on each of 8 CTs of a 4DCT set.</p> <p>Results</p> <p>In the phantom measurements, the MC dose engine showed discrepancies < 2%, while the fsPB dose engine showed discrepancies of up to 8% in the presence of lateral electron disequilibrium in the target. In the patient plan optimization, this translates into violations of organ at risk constraints and unpredictable target doses for the fsPB optimized plans. For the 4D MC recalculated dose distribution, MC optimized plans always underestimate the target doses, but the organ at risk doses were comparable. The results depend on the static patient model, and the smallest discrepancy was found for the MC optimized plan on the density overwrite one phase static CT model.</p> <p>Conclusions</p> <p>It is feasible to employ the MC dose engine for optimization of lung IMSRT and the plans are superior to fsPB. Use of static patient models introduces a bias in the MC dose distribution compared to the 4D MC recalculated dose, but this bias is predictable and therefore MC based optimization on static patient models is considered safe.</p

HPK1 Associates with SKAP-HOM to Negatively Regulate Rap1-Mediated B-Lymphocyte Adhesion

BACKGROUND: Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-related serine/threonine kinase activated by a range of environmental stimuli including genotoxic stress, growth factors, inflammatory cytokines and antigen receptor triggering. Being inducibly recruited to membrane-proximal signalling scaffolds to regulate NFAT, AP-1 and NFkappaB-mediated gene transcription in T-cells, the function of HPK1 in B-cells to date remains rather ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: By using two loss of function models, we show that HPK1 displays a novel function in regulating B-cell integrin activity. Wehi 231 lymphoma cells lacking HPK1 after shRNA mediated knockdown exhibit increased basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation and increased adhesion to intercellular adhesion molecule 1 (ICAM-1). The observed phenotype of enhanced integrin activity is caused downstream of Src, by a signalling module independent of PI3K and PLC, involving HPK1, SKAP55 homologue (SKAP-HOM) and Rap1-GTP-interacting adaptor molecule (RIAM). This alters actin dynamics and renders focal adhesion kinase (FAK) constitutively phosphorylated. Bone marrow and splenic B-cell development of HPK1(-/-) mice are largely unaffected, except age-related tendencies for increased splenic cellularity and BCR downregulation. In addition, naïve splenic knockout B-cells appear hyperresponsive to a range of stimuli applied ex vivo as recently demonstrated by others for T-cells. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that HPK1 exhibits a dual function in B-cells by negatively regulating integrin activity and controlling cellular activation, which makes it an interesting candidate to study in pathological settings like autoimmunity and cancer

A physiological time analysis of the duration of the gonotrophic cycle of Anopheles pseudopunctipennis and its implications for malaria transmission in Bolivia

<p>Abstract</p> <p>Background</p> <p>The length of the gonotrophic cycle varies the vectorial capacity of a mosquito vector and therefore its exact estimation is important in epidemiological modelling. Because the gonotrophic cycle length depends on temperature, its estimation can be satisfactorily computed by means of physiological time analysis.</p> <p>Methods</p> <p>A model of physiological time was developed and calibrated for <it>Anopheles pseudopunctipennis</it>, one of the main malaria vectors in South America, using data from laboratory temperature controlled experiments. The model was validated under varying temperatures and could predict the time elapsed from blood engorgement to oviposition according to the temperature.</p> <p>Results</p> <p>In laboratory experiments, a batch of <it>An. pseudopunctipennis </it>fed at the same time may lay eggs during several consecutive nights (2–3 at high temperature and > 10 at low temperature). The model took into account such pattern and was used to predict the range of the gonotrophic cycle duration of <it>An. pseudopunctipennis </it>in four characteristic sites of Bolivia. It showed that the predicted cycle duration for <it>An. pseudopunctipennis </it>exhibited a seasonal pattern, with higher variances where climatic conditions were less stable. Predicted mean values of the (minimum) duration ranged from 3.3 days up to > 10 days, depending on the season and the geographical location. The analysis of ovaries development stages of field collected biting mosquitoes indicated that the phase 1 of Beklemishev might be of significant duration for <it>An. pseudopunctipennis</it>. The gonotrophic cycle length of <it>An. pseudopunctipennis </it>correlates with malaria transmission patterns observed in Bolivia which depend on locations and seasons.</p> <p>Conclusion</p> <p>A new presentation of cycle length results taking into account the number of ovipositing nights and the proportion of mosquitoes laying eggs is suggested. The present approach using physiological time analysis might serve as an outline to other similar studies and allows the inclusion of temperature effects on the gonotrophic cycle in transmission models. However, to better explore the effects of temperature on malaria transmission, the others parameters of the vectorial capacity should be included in the analysis and modelled accordingly.</p

Diagnosing delirium in elderly Thai patients: Utilization of the CAM algorithm

<p>Abstract</p> <p>Background</p> <p>Delirium is a common illness among elderly hospitalized patients. However, under-recognition of the condition by non-psychiatrically trained personnel is prevalent. This study investigated the performance of family physicians when detecting delirum in elderly hospitalized Thai patients using the Thai version of the Confusion Assessment Method (CAM) algorithm.</p> <p>Methods</p> <p>A Thai version of the CAM algorithm was developed, and three experienced Thai family physicians were trained in its use. The diagnosis of delirium was also carried out by four fully qualified psychiatrists using DSM-IV TR criteria, which can be considered the gold standard. Sixty-six elderly patients were assessed with MMSE Thai 2002, in order to evaluate whether they had dementia upon admission. Within three days of admission, each patient was interviewed separately by a psychiatrist using DSM-IV TR, and a family physician using the Thai version of the CAM algorithm, with both sets of interviewers diagnosing for delirium.</p> <p>Results</p> <p>The CAM algorithm tool, as used by family physicians, demonstrated a sensitivity of 91.9% and a specificity of 100.0%, with a PPV of 100.0% and an NPV of 90.6%. Interrater agreement between the family physicians and the psychiatrists was good (Cohen's Kappa = 0.91, p < 0.0001). The mean of the time the family physicians spent using CAM algorithm was significantly briefer than that of the psychiatrists using DSM-IV TR.</p> <p>Conclusions</p> <p>Family physicians performed well when diagnosing delirium in elderly hospitalized Thai patients using the Thai version of the CAM algorithm, showing that this measurement tool is suitable for use by non-psychiatrically trained personnel, being short, quick, and easy to administer. However, proper training on use of the algorithm is required.</p