Inhibiting Ca2+ channels in Alzheimer's disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia.

Early in Alzheimer's disease (AD), pericytes constrict capillaries, increasing their hydraulic resistance and trapping of immune cells and, thus, decreasing cerebral blood flow (CBF). Therapeutic approaches to attenuate pericyte-mediated constriction in AD are lacking. Here, using in vivo two-photon imaging with laser Doppler and speckle flowmetry and magnetic resonance imaging, we show that Ca2+ entry via L-type voltage-gated calcium channels (CaVs) controls the contractile tone of pericytes. In AD model mice, we identifed pericytes throughout the capillary bed as key drivers of an immune reactive oxygen species (ROS)-evoked and pericyte intracellular calcium concentration ([Ca2+]i)-mediated decrease in microvascular flow. Blocking CaVs with nimodipine early in disease progression improved CBF, reduced leukocyte stalling at pericyte somata and attenuated brain hypoxia. Amyloid ß (Aß)-evoked pericyte contraction in human cortical tissue was also greatly reduced by CaV block. Lowering pericyte [Ca2+]i early in AD may, thus, offer a therapeutic strategy to enhance brain energy supply and possibly cognitive function in AD.

Molecular and Phylogenetic Evidence of Interfamilial Transmission of HTLV-1 in the Afro-Descendant Community of São José de Icatú in the Brazilian Amazon.

This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence.

Immunogenetic Profile Associated with Patients Living with HIV-1 and Epstein-Barr Virus (EBV) in the Brazilian Amazon Region.

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-É£, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

Sociobehavioral Risk Factors and Clinical Implications of Late Presentation Among People Living with HIV in the Brazilian Amazon Region.

This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region.

Background: Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients. Methods: We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO. Results: The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection. Conclusion: Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

Identification of eQTLs using different sets of single nucleotide polymorphisms associated with carcass and body composition traits in pigs.

BACKGROUND: Mapping expression quantitative trait loci (eQTLs) in skeletal muscle tissue in pigs is crucial for understanding the relationship between genetic variation and phenotypic expression of carcass traits in meat animals. Therefore, the primary objective of this study was to evaluate the impact of different sets of single nucleotide polymorphisms (SNP), including scenarios removing SNPs pruned for linkage disequilibrium (LD) and SNPs derived from SNP chip arrays and RNA-seq data from liver, brain, and skeletal muscle tissues, on the identification of eQTLs in the Longissimus lumborum tissue, associated with carcass and body composition traits in Large White pigs. The SNPs identified from muscle mRNA were combined with SNPs identified in the brain and liver tissue transcriptomes, as well as SNPs from the GGP Porcine 50 K SNP chip array. Cis- and trans-eQTLs were identified based on the skeletal muscle gene expression level, followed by functional genomic analyses and statistical associations with carcass and body composition traits in Large White pigs. RESULTS: The number of cis- and trans-eQTLs identified across different sets of SNPs (scenarios) ranged from 261 to 2,539 and from 29 to 13,721, respectively. Furthermore, 6,180 genes were modulated by eQTLs in at least one of the scenarios evaluated. The eQTLs identified were not significantly associated with carcass and body composition traits but were significantly enriched for many traits in the "Meat and Carcass" type QTL. The scenarios with the highest number of cis- (n = 304) and trans- (n = 5,993) modulated genes were the unpruned and LD-pruned SNP set scenarios identified from the muscle transcriptome. These genes include 84 transcription factor coding genes. CONCLUSIONS: After LD pruning, the set of SNPs identified based on the transcriptome of the skeletal muscle tissue of pigs resulted in the highest number of genes modulated by eQTLs. Most eQTLs are of the trans type and are associated with genes influencing complex traits in pigs, such as transcription factors and enhancers. Furthermore, the incorporation of SNPs from other genomic regions to the set of SNPs identified in the porcine skeletal muscle transcriptome contributed to the identification of eQTLs that had not been identified based on the porcine skeletal muscle transcriptome alone.

Evaluation of Severe Acute Respiratory Syndrome surveillance caused by respiratory viruses in a pediatric unit, 2013 to 2019 / Avaliação da vigilância da Síndrome Respiratória Aguda Grave causada por vírus respiratórios em uma unidade pediátrica, 2013 a 2019

ABSTRACT Objective: To evaluate severe acute respiratory syndrome surveillance in a pediatric unit. Methods: Descriptive study of reported severe acute respiratory syndrome cases with the detection of respiratory viruses in the nasopharyngeal sample of patients hospitalized between 2013 and 2019, in a reference hospital in the Federal District, Brazil. Results: A total of 269 children had one or more viruses detected, resulting in 280 viruses, of which 152 (54%) were respiratory syncytial virus. The detection of respiratory syncytial virus was higher during the autumn-winter period. Children´s median age was 6.9 months, 156 (58%) were male, 104 (39%) had comorbidity, 197 (73%) required mechanical ventilation, 241 (90%) received antibiotics, and 146 (54%) oseltamivir. There were 19 (7%) deaths. The median time from symptom onset to sample collection was 5 days and the median time from sample collection to final results was 6 days. Conclusions: The system needs to reduce the time to deliver results so that inappropriate use of antibiotics and antivirals can be avoided. Moreover, the burden of viral pneumonia was relevant and the system must be flexible enough to include emerging viruses in order to be useful in responding to public health emergencies caused by respiratory viruses.

RESUMO Objetivo: Avaliar a vigilância da síndrome respiratória aguda grave em uma unidade pediátrica. Métodos: Estudo descritivo dos casos de síndrome respiratória aguda grave, notificados e com a detecção de vírus respiratório em amostra de nasofaringe de pacientes internados entre 2013 e 2019, em um hospital de referência do Distrito Federal. Resultados: Um total de 269 crianças tiveram algum vírus detectado, resultando em 280 vírus, sendo 152 (54%) vírus sincicial respiratório. A detecção do vírus sincicial respiratório foi maior durante o período de outono-inverno. A mediana da idade das crianças foi de 6,9 meses, 156 (58%) eram do sexo masculino, 104 (39%) tinham comorbidade, 197 (73%) necessitaram de ventilação mecânica, 241 (90%) receberam antibióticos e 146 (54%) oseltamivir. Ocorreram 19 (7%) óbitos. A mediana do tempo desde o início dos sintomas até a coleta da amostra foi de 5 dias, e do tempo da coleta até o resultado foi de 6 dias. Conclusões: O sistema necessita reduzir o tempo do resultado final para que seja possível evitar o uso inadequado de antibióticos e antivirais. Ademais, o impacto das pneumonias virais foi relevante e o sistema deve ser flexível suficiente para incluir vírus emergentes, para ser útil na resposta às emergências de saúde pública causada por vírus respiratórios.

Antimicrobial resistance and epidemic clustering of late-onset neonatal infections in a Brazilian intensive care unit.

Nosocomial infections in the neonatal intensive care unit (NICU) tend to cluster and multidrug-resistant (MDR) pathogens are rising in developing countries. We did a retrospective cohort study of neonates admitted to a NICU in Brazil with late-onset neonatal sepsis (LOS) confirmed by blood culture from October 2012 to December 2016 and from July 2018 to December 2021. We defined a cluster of infection when at least two cases of LOS occurred within two different time intervals: 15 and 30 days with the same pathogen in different patients. A random amplified polymorphic DNA (RAPD) was performed from samples from one of these clusters. A logistic regression model was applied having death as the outcome and the infection with an MDR pathogen as the exposure of interest. There were 987 blood cultures from 754 neonates, 621 (63%) were gram-positive cocci, 264 (30%) were gram-negative rods and 72 (7%) fungi. A third of Enterobacterales were resistant to cefepime and a third of non-fermenting glucose rods were resistant to carbapenems. There were 100 or 104 clusters of infection in the 15- or 30-day interval, respectively. A RAPD analysis from an outbreak of MDR Acinetobacter baumannii showed that all five samples belonged to a single clone. An infection with an MDR pathogen was associated with death (OR 1.82, 95% CI 1.03-3.21). In conclusion, clusters of infections in a Brazilian NICU are a frequent phenomenon as seen elsewhere. They suggest cross-transmission of pathogens with increasing antimicrobial resistance and should prompt intensified surveillance and infection control measures.

Equine conjunctival haemangiosarcoma: Clinical presentation, management, and outcome of seven cases in the United Kingdom.

Background: Only 27 cases of equine conjunctival haemangiosarcoma have been reported in the literature over the past 37 years. Out of these, 22% of cases were lost to follow-up, 52% were euthanized, and 26% survived. A scarcity of cases and information is available for this rarely seen conjunctival tumour. Aim: To describe the clinical features, management, and outcome of conjunctival hemangiosarcoma in seven horses in the UK. Methods: Optivet medical records were reviewed for equine cases seen or advised on with a histopathological diagnosis of conjunctival haemangiosarcoma between January 2013 and March 2023. Medical records were accessed for details of signalment, history, management, and follow-up. Histopathology was used to confirm the diagnosis of haemangiosarcoma and assess the surgical margins. Immunohistochemistry was performed in a minority of cases with poorly differentiated solid tumours to support vascular lineage. Results: Seven eyes from seven horses (five geldings and two mares) with a mean age of 16 years and median of 18 years (range 10-21 years) met the criteria. Serosanguinous discharge was seen in six eyes. All eyes were managed surgically; 4 by exenteration and 3 by conjunctivectomy/keratectomy. Adjunctive cryotherapy was performed in two eyes. Metastatic disease in the ipsilateral parotid salivary gland, confirmed with histopathology, was seen in one horse. Surgical margins were clear in all but one eye. Solar elastosis was noted in five eyes. All horses were healthy at the last follow-up (0.2-5 years, mean 2.9 years, and median 2 years). Conclusion: Equine conjunctival haemangiosarcoma is rare. Serosanguinous ocular discharge is a common clinical sign. Early surgical excision is highly effective. Solar elastosis is a common histopathological feature, suggesting a role for UV-light in the pathogenesis.

Evaluation of Severe Acute Respiratory Syndrome surveillance caused by respiratory viruses in a pediatric unit, 2013 to 2019.

OBJECTIVE: To evaluate severe acute respiratory syndrome surveillance in a pediatric unit. METHODS: Descriptive study of reported severe acute respiratory syndrome cases with the detection of respiratory viruses in the nasopharyngeal sample of patients hospitalized between 2013 and 2019, in a reference hospital in the Federal District, Brazil. RESULTS: A total of 269 children had one or more viruses detected, resulting in 280 viruses, of which 152 (54%) were respiratory syncytial virus. The detection of respiratory syncytial virus was higher during the autumn-winter period. Children´s median age was 6.9 months, 156 (58%) were male, 104 (39%) had comorbidity, 197 (73%) required mechanical ventilation, 241 (90%) received antibiotics, and 146 (54%) oseltamivir. There were 19 (7%) deaths. The median time from symptom onset to sample collection was 5 days and the median time from sample collection to final results was 6 days. CONCLUSIONS: The system needs to reduce the time to deliver results so that inappropriate use of antibiotics and antivirals can be avoided. Moreover, the burden of viral pneumonia was relevant and the system must be flexible enough to include emerging viruses in order to be useful in responding to public health emergencies caused by respiratory viruses.

The evolutionary history of bees in time and space.

Bees are the most significant pollinators of flowering plants. This partnership began ca. 120 million years ago, but the uncertainty of how and when bees spread across the planet has greatly obscured investigations of this key mutualism. We present a novel analysis of bee biogeography using extensive new genomic and fossil data to demonstrate that bees originated in Western Gondwana (Africa and South America). Bees likely originated in the Early Cretaceous, shortly before the breakup of Western Gondwana, and the early evolution of any major bee lineage is associated with either the South American or African land masses. Subsequently, bees colonized northern continents via a complex history of vicariance and dispersal. The notable early absences from large landmasses, particularly in Australia and India, have important implications for understanding the assembly of local floras and diverse modes of pollination. How bees spread around the world from their hypothesized Southern Hemisphere origin parallels the histories of numerous flowering plant clades, providing an essential step to studying the evolution of angiosperm pollination syndromes in space and time.

Transcriptome profile of skeletal muscle using different sources of dietary fatty acids in male pigs.

Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 32 DEG for CO vs FO, and 531 DEG for SOY vs FO comparison. Several genes, including AZGP1, PDE3B, APOE, PLIN1, and LIPS, were found to be down-regulated in the diet of the SOY group compared to the FO group. The enrichment analysis revealed DEG involved in lipid metabolism, metabolic diseases, and inflammation between the oil groups, with specific gene functions in each group and altered blood parameters. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil.

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

RNA-seq transcriptome profiling of pigs' liver in response to diet with different sources of fatty acids.

Pigs (Sus scrofa) are an animal model for metabolic diseases in humans. Pork is an important source of fatty acids (FAs) in the human diet, as it is one of the most consumed meats worldwide. The effects of dietary inclusion of oils such as canola, fish, and soybean oils on pig gene expression are mostly unknown. Our objective was to evaluate FA composition, identify changes in gene expression in the liver of male pigs fed diets enriched with different FA profiles, and identify impacted metabolic pathways and gene networks to enlighten the biological mechanisms' variation. Large White male pigs were randomly allocated to one of three diets with 18 pigs in each; all diets comprised a base of corn and soybean meal to which either 3% of soybean oil (SOY), 3% canola oil (CO), or 3% fish oil (FO) was added for a 98-day trial during the growing and finishing phases. RNA sequencing was performed on the liver samples of each animal by Illumina technology for differential gene expression analyses, using the R package DESeq2. The diets modified the FA profile, mainly in relation to polyunsaturated and saturated FAs. Comparing SOY vs. FO, 143 differentially expressed genes (DEGs) were identified as being associated with metabolism, metabolic and neurodegenerative disease pathways, inflammatory processes, and immune response networks. Comparing CO vs. SOY, 148 DEGs were identified, with pathways related to FA oxidation, regulation of lipid metabolism, and metabolic and neurodegenerative diseases. Our results help explain the behavior of genes with differential expression in metabolic pathways resulting from feeding different types of oils in pig diets.

Assessment of the Accuracy, Usability and Acceptability of a Rapid Test for the Simultaneous Diagnosis of Syphilis and HIV Infection in a Real-Life Scenario in the Amazon Region, Brazil.

We field-assessed the accuracy, acceptability, and feasibility of the SD BIOLINE HIV/Syphilis Duo rapid diagnostic test in three groups: pregnant women, female sex workers (FSW), and men who have sex with men (MSM). Venous blood samples collected in the field were compared with the respective gold standard methods: SD BIOLINE HIV/Syphilis Duo Treponemal Test versus FTA-abs (Wama brand) treponemal laboratory test for syphilis, and SD BIOLINE HIV/Syphilis Duo Test versus the fourth generation Genscreen Ultra HIV Ag-Ag (Bio-Rad brand) laboratory test for HIV. From a total of 529 participants, 397 (75.1%) were pregnant women, 76 (14.3%) FSW and 56 (10.6%) MSM. Sensitivity and specificity parameters of HIV were 100.0% (95% CI: 82.35-100.0%) and 100.0% (95% CI: 99.28-100.0%), respectively. Sensitivity and specificity parameters found for TP antibody detection were 95.00% (95% CI: 87.69-98.62%) and 100.0% (95% CI: 98.18-100.0%), respectively. The SD BIOLINE HIV/Syphilis Duo Test showed high acceptability among participants (85.87%) and health professionals (85.51%), as well as easy usability by professionals (91.06%). The usability of the SD BIOLINE HIV/Syphilis Duo Test kit would not be a barrier to accessing rapid testing, if the product were incorporated into the list of health service supplies.

Evaluating the Impact of Anatomical Partitioning on Summary Topologies Obtained with Bayesian Phylogenetic Analyses of Morphological Data.

Morphological data are a fundamental source of evidence to reconstruct the Tree of Life, and Bayesian phylogenetic methods are increasingly being used for this task. Bayesian phylogenetic analyses require the use of evolutionary models, which have been intensively studied in the past few years, with significant improvements to our knowledge. Notwithstanding, a systematic evaluation of the performance of partitioned models for morphological data has never been performed. Here we evaluate the influence of partitioned models, defined by anatomical criteria, on the precision and accuracy of summary tree topologies considering the effects of model misspecification. We simulated datasets using partitioning schemes, trees, and other properties obtained from two empirical datasets, and conducted Bayesian phylogenetic analyses. Additionally, we reanalyzed 32 empirical datasets for different groups of vertebrates, applying unpartitioned and partitioned models, and, as a focused study case, we reanalyzed a dataset including living and fossil armadillos, testing alternative partitioning hypotheses based on functional and ontogenetic modules. We found that, in general, partitioning by anatomy has little influence on summary topologies analyzed under alternative partitioning schemes with a varying number of partitions. Nevertheless, models with unlinked branch lengths, which account for heterotachy across partitions, improve topological precision at the cost of reducing accuracy. In some instances, more complex partitioning schemes led to topological changes, as tested for armadillos, mostly associated with models with unlinked branch lengths. We compare our results with other empirical evaluations of morphological data and those from empirical and simulation studies of the partitioning of molecular data, considering the adequacy of anatomical partitioning relative to alternative methods of partitioning morphological datasets. [Evolutionary rates; heterogeneity; morphology; Mk model; partition; topology.].

SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction.

The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II evoked a small pericyte-mediated capillary constriction via AT1 receptors, but evoked a large constriction when the SARS-CoV-2 receptor binding domain (RBD, original Wuhan variant) was present. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices, and was evoked in hamster brain slices by pseudotyped virions expressing SARS-CoV-2 spike protein. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7) mediated by removal of ACE2 from the cell surface membrane and was mimicked by blocking ACE2. The clinically used drug losartan inhibited the RBD-potentiated constriction. Thus, AT1 receptor blockers could be protective in COVID-19 by preventing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.

A pandemia do novo coronavírus: psicopolítica e biovigilância / La nueva pandemia de coronavirus: psicopolítica y biovigilancia / The new coronavirus pandemic: psychopolitics and biovigilance

RESUMO Este artigo teve o objetivo de criar um ensaio teórico a respeito da biopolítica diante da expansão do contágio pelo novo coronavírus. Por meio de trabalhos analíticos sobre o aumento das tecnologias de biovigilância face à pandemia por Covid-19, buscou-se neste texto alcançar uma perspectiva dos processos acontecimentais em curso na sociedade contemporânea em nome da defesa social e da gestão da vida. Estudos de Michel Foucault, de Han e Bauman auxiliaram nesta proposta de problematização das práticas de controle e segurança implantadas em nome do fazer viver e do deixar morrer em andamento, no neoliberalismo atual. Portanto, abordou-se um plano psicopolítico e filosófico social da pandemia e de seus efeitos na medida em que se configurou um processo minucioso da expansão da doença, do contágio e dos modos de lidar com estes acontecimentos complexos. Assim, o artigo apresentou um ensaio teórico sobre os usos autoritários de biovigilância durante a pandemia e a descrição de alguns dos seus efeitos e modos de materialidade.

RESUMEN Este artículo tuvo como objetivo crear un ensayo teórico sobre biopolítica en vista de la propagación del contagio por el nuevo coronavirus. A través del trabajo analítico sobre el aumento de las tecnologías de biovigilancia ante la pandemia de Covid-19, este texto buscó alcanzar una perspectiva de los procesos que suceden en la sociedad contemporánea en nombre de la defensa social y la gestión de la vida. Los estudios de Michel Foucault, Han y Bauman ayudaron en esta propuesta a problematizar las prácticas de control y seguridad implementadas en nombre de hacer la vida y dejar morir en progreso, en el neoliberalismo actual. Por lo tanto, un plan social psicopolítico y filosófico de la pandemia y sus efectos se abordaron como un proceso detallado de propagación de la enfermedad, el contagio y las formas de lidiar con estos eventos complejos. Así, el artículo presentó un ensayo teórico sobre los usos autoritarios de la biovigilancia durante la pandemia y la descripción de algunos de sus efectos y modos de materialidad.

ABSTRACT This article aimed to create a theoretical essay about biopolitics in view of the spread of contagion by the new coronavirus. Through analytical work on the increase in biovigilance technologies in the face of the pandemic by Covid-19, this text sought to achieve a perspective of the happening processes in contemporary society in the name of social defense and life management. Studies by Michel Foucault, Han and Bauman helped in this proposal to problematize the control and security practices implemented in the name of making life and letting die in progress, in the current neoliberalism. Therefore, a social psychopolitical and philosophical plan for the pandemic and its effects was approached, as a detailed process of spreading the disease, contagion and ways of dealing with these complex events took shape. Thus, the article presented a theoretical essay on the authoritarian uses of biovigilance during the pandemic and the description of some of its effects and modes of materiality.

Benthic Dissolved Silicon and Iron Cycling at Glaciated Patagonian Fjord Heads.

Glacier meltwater supplies silicon (Si) and iron (Fe) sourced from weathered bedrock to downstream ecosystems. However, the extent to which these nutrients reach the ocean is regulated by the nature of the benthic cycling of dissolved Si and Fe within fjord systems, given the rapid deposition of reactive particulate fractions at fjord heads. Here, we examine the benthic cycling of the two nutrients at four Patagonian fjord heads through geochemical analyses of sediment pore waters, including Si and Fe isotopes (δ30Si and δ56Fe), and reaction-transport modeling for Si. A high diffusive flux of dissolved Fe from the fjord sediments (up to 0.02 mmol m-2 day-1) compared to open ocean sediments (typically <0.001 mmol m-2 day-1) is supported by both reductive and non-reductive dissolution of glacially-sourced reactive Fe phases, as reflected by the range of pore water δ56Fe (-2.7 to +0.8‰). In contrast, the diffusive flux of dissolved Si from the fjord sediments (0.02-0.05 mmol m-2 day-1) is relatively low (typical ocean values are >0.1 mmol m-2 day-1). High pore water δ30Si (up to +3.3‰) observed near the Fe(II)-Fe(III) redox boundary is likely associated with the removal of dissolved Si by Fe(III) mineral phases, which, together with high sedimentation rates, contribute to the low diffusive flux of Si at the sampled sites. Our results suggest that early diagenesis promotes the release of dissolved Fe, yet suppresses the release of dissolved Si at glaciated fjord heads, which has significant implications for understanding the downstream transport of these nutrients along fjord systems.