Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice

Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system

Role of the gp85/Trans-Sialidases in Trypanosoma cruzi Tissue Tropism: Preferential Binding of a Conserved Peptide Motif to the Vasculature in Vivo

Background: Transmitted by blood-sucking insects, the unicellular parasite Trypanosoma cruzi is the causative agent of Chagas' disease, a malady manifested in a variety of symptoms from heart disease to digestive and urinary tract dysfunctions. the reasons for such organ preference have been a matter of great interest in the field, particularly because the parasite can invade nearly every cell line and it can be found in most tissues following an infection. Among the molecular factors that contribute to virulence is a large multigene family of proteins known as gp85/trans-sialidase, which participates in cell attachment and invasion. But whether these proteins also contribute to tissue homing had not yet been investigated. Here, a combination of endothelial cell immortalization and phage display techniques has been used to investigate the role of gp85/trans-sialidase in binding to the vasculature.Methods: Bacteriophage expressing an important peptide motif (denominated FLY) common to all gp85/trans-sialidase proteins was used as a surrogate to investigate the interaction of this motif with the endothelium compartment. for that purpose phage particles were incubated with endothelial cells obtained from different organs or injected into mice intravenously and the number of phage particles bound to cells or tissues was determined. Binding of phages to intermediate filament proteins has also been studied.Findings and Conclusions: Our data indicate that FLY interacts with the endothelium in an organ-dependent manner with significantly higher avidity for the heart vasculature. Phage display results also show that FLY interaction with intermediate filament proteins is not limited to cytokeratin 18 (CK18), which may explain the wide variety of cells infected by the parasite. This is the first time that members of the intermediate filaments in general, constituted by a large group of ubiquitously expressed proteins, have been implicated in T. cruzi cell invasion and tissue homing.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv São Paulo, Inst Quim, Dept Bioquim, BR-01498 São Paulo, BrazilUniv Texas MD Anderson Canc Ctr, David H Koch Ctr, Houston, TX 77030 USAUniv Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USAUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFAPESP: 2004/03303-5FAPESP: 2008/54.806-8Web of Scienc

Global summer schools: developing multicultural competencies staying at home

International summer schools are a well know approach to improve technical skills as well as to develop multicultural competencies (Lerke, 2020). University students benefit particularly from these as they can also learn specialist knowledge which might inspire them to pursue a specific research topic or to consider options abroad for further education or employment after graduation. The global disruption of COVID-19 prevented international summer schools in 2020 and 2021, and continues to restrict international travel, with some higher education institutions holding a stricter policy to protect students and staff, limiting travel until further notice. A virtual alternative global summer school was coordinated by an international team of universities: Unidad Profesional Interdisciplinaria de Biotecnologia (UPIBI-IPN, Mexico), Escuela Nacional de Educacion Superior-Juriquilla (ENES-Juriquilla, Mexico), Universita de Piemonte Orientale-Novara (UPO-Novara, Italy) and Manchester Metropolitan University (MMU, UK) to enable students in biomed/biotech/bioeng areas, to experience a virtual summer school, supporting their employability while fostering international academic collaborations between departments. The aim was to deliver an online summer school that would provide an insight into the latest research projects, as much as, allow students to learn about other cultures. The programme was planned for 66% for scientific talks, and 33% cultural talks, the latter including virtual tours of cities, live food sessions, recorded videos of participants performing folkloric dances and introduction to languages. The programme ran over four days, each hosted by a different institution. Prior institutional experience on blended teaching and virtual collaborations allowed the team to run the online school with appropriate technologies to coordinate questions and polls to monitor students’ experience and assess their learning. The official language of the programme was English; speakers, chairs and coordinators connected via zoom, with sessions being watched by 200long-term viewers in Facebook live and Youtube live. Sessions were interactive with quizzes and polls using Kahoot and Vevox, the latter, allowed real time data analysis to compare the perception of students about their multicultural and scientific experience. Finally, students were assessed on the scientific content with a final VLE MCQ, which also allowed one institution (UPO) to award credits for a module, and another institution (MMU) to provide extracurricular points for their RISE Award. Student engagement was constant and feedback showed their satisfaction for attending a summer school that not only exposed them to high-quality international research, but also to other cultures; with data showing 66% of students enjoyed cultural sessions as much as scientific talks (n=35±10). In addition, 95% of students confirmed that they were more likely to travel to one of the hosting countries, and 93% more likely to learn one of the hosting languages after the global summer school, indicating a strong correlation between a virtual international activity, and an inclusive attitude and new-found multicultural proficiency. Despite the success, our current structure should evolve to include virtual spaces to facilitate group work and students’ interactions (de Hei, 2020) to assist intercultural learning and complement the high-quality scientific engagement and the rich cultural exchange

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Theory of Mind and its elusive structural substrate

Is brain structure related to function? Can one predict the other? These are questions that are still waiting to be answered definitively. In this paper we seek to investigate these questions, in particular, we are interested in the relation between brain structure and theory of mind (ToM). ToM is defined as the ability to attribute mental states to others. Previous studies have observed correlations between performance on ToM tasks, and grey-matter size/volume in dorsomedial prefrontal cortex (dmPFC), temporoparietal junction (TPJ) and precuneus (PCu). Despite these findings, there are concerns about false positive results and replicability issues. In this study we used two different tasks to evaluate ToM, Reading the Mind in the Eyes Test (RMET), and the Short Story Task (SST). Performance in these tasks was correlated to brain anatomy measures including voxel-based morphometry (VBM) and cortical thickness (CT) analysis, from ninety-one neurotypical participants. High-resolution structural brain images were acquired, and whole-brain and region of interest (ROI) analyses were implemented. The analyses did not show statistically significant associations between ToM performance and brain structural measures after correction. Significant associations between performance on ToM tests and a widespread array of regions loosely associated with ToM were observed only for whole brain uncorrected analysis analysis (p < 0.001). These results do not replicate a previous study with neurotypical participants (Sato et al., 2016). We tested two different ToM tests, two different softwares for VBM and CT, and we used two samples, one with 91 and a sub-sample with 69 participants. Neither of these conditions made a difference in the results obtained. Consequently, these results suggest that if the population is neurotypical and homogenous, it is unlikely that a reliable association between brain anatomy measures and ToM performance, as measured with these tasks, may be found

Contribution and functional connectivity between cerebrum and cerebellum on sub-lexical and lexical-semantic processing of verbs.

Language comprehension involves both sub-lexical (e.g., phonological) and lexical-semantic processing. We conducted a task using functional magnetic resonance imaging (fMRI) to compare the processing of verbs in these two domains. Additionally, we examined the representation of concrete-motor and abstract-non-motor concepts by including two semantic categories of verbs: motor and mental. The findings indicate that sub-lexical processing during the reading of pseudo-verbs primarily involves the left dorsal stream of the perisylvian network, while lexical-semantic representation during the reading of verbs predominantly engages the ventral stream. According to the embodied or grounded cognition approach, modality-specific mechanisms (such as sensory-motor systems) and the well-established multimodal left perisylvian network contribute to the semantic representation of both concrete and abstract verbs. Our study identified the visual system as a preferential modality-specific system for abstract-mental verbs, which exhibited functional connectivity with the right crus I/lobule VI of the cerebellum. Taken together, these results confirm the dissociation between sub-lexical and lexical-semantic processing and provide neurobiological evidence of functional coupling between specific visual modality regions and the right cerebellum, forming a network that supports the semantic representation of abstract concepts. Further, the results shed light on the underlying mechanisms of semantic processing and contribute to our understanding of how the brain processes abstract concepts