A C-type lectin from Bothrops jararacussu venom reprograms endothelial cell biology.

Snake venoms are intricate mixtures of enzymes and bioactive factors that induce a range of detrimental effects in afflicted hosts. Certain Viperids, including Bothrops jararacussu, harbor C-type lectins (CTLs) known for their modulation of a variety of host cellular responses. In this study, we isolated and purified BjcuL, a CTL from B. jararacussu venom and investigated its impact on endothelial cell behavior, contrasting it with human galectin-1 (Gal-1), a prototype member of the galectin family with shared ß-galactoside-binding activity. We found that BjcuL binds to human dermal microvascular endothelial cells (HMECs) in a concentration- and carbohydrate-dependent fashion and reprograms the function of these cells, favoring a pro-inflammatory and pro-coagulant endothelial phenotype. In light of the quest for universal antagonists capable of mitigating the harmful consequences of snake venoms, BjcuL emerges as a promising target to be blocked in order to regulate pathological endothelial cell responses.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.

Generation of heterozygous (MCRIi030-A-1) and homozygous (MCRIi030-A-2) NR2F2/COUP-TFII knockout human iPSC lines.

The NR2F2 gene encodes the transcription factor COUP-TFII, which is upregulated in embryonic mesoderm. Heterozygous variants in NR2F2 cause a spectrum of congenital anomalies including cardiac and gonadal phenotypes. We generated heterozygous (MCRIi030-A-1) and homozygous (MCRIi030-A-2) NR2F2-knockout induced pluripotent stem cell (iPSC) lines from human fibroblasts using a one-step protocol for CRISPR/Cas9 gene-editing and episomal-based reprogramming. Both iPSC lines exhibited a normal karyotype, typical pluripotent cell morphology, pluripotency marker expression, and the capacity to differentiate into the three embryonic germ layers. These lines will allow us to explore the role of NR2F2 during development and disease.

New records of soft ticks (Acari: Argasidae) from caves in Brazil, with a morphological study of Ornithodoros fonsecai and an analysis of the taxonomic status of Antricola inexpectata.

In this study, we report soft ticks from bat-inhabiting caves in different areas of Brazil. From 2010 to 2019, we collected 807 tick specimens from nine caves located in four Brazilian states among two biomes. Ticks were morphologically identified as Antricola guglielmonei (282 specimens), Ornithodoros cavernicolous (260 specimens), and Ornithodoros fonsecai (265 specimens). Whereas A. guglielmonei was collected on bat guano in hot caves, O. cavernicolous and O. fonsecai were collected in cracks and crevices on the walls of cold caves, sometimes in the same chamber. Morphological identifications were corroborated by molecular and phylogenetic analyses inferred from tick mitochondrial 16S rRNA gene partial sequences. The sequences of A. guglielmonei, O. cavernicolous and O. fonsecai collected in this study clustered with conspecific GenBank sequences from different localities of Brazil. Remarkably, a clade containing 12 sequences of O. fonsecai was clearly bifurcated, denoting a degree of genetic divergence (up to 5 %) of specimens from Cerrado/Atlantic Forest biomes with the specimens from the Caatinga biome. To further evaluate this divergence, we performed morphometric analysis of the larval stage of different O. fonsencai populations by principal component analysis, which indicated that the larvae from Caatinga populations were generally smaller than the larvae from other biomes. Some of the present A. guglielmonei specimens were collected from the type locality of Antricola inexpectata. Comparisons of these specimens with the type specimens of A. inexpectata and A. guglielmonei indicated that they could not be separated by their external morphology. Hence, we are relegating A. inexpectata to a synonym of A. guglielmonei. This proposal is corroborated by our phylogenetic analysis.

Characterization of Escherichia coli Isolated from Sows Presenting Purulent Vulvar Discharge.

Purulent vulvar discharge is a clinical sign of genitourinary tract infections, which are a significant concern in swine facilities, leading to sow culling and mortality. Escherichia coli is one of the main agents involved in these diseases. This study aimed to characterize the virulence and antimicrobial resistance profiles as well as the phylotype of Escherichia coli strains isolated from sows with purulent vulvar discharge. The results showed that at least 2 of the 29 tested virulence genes related to extraintestinal pathogenic E. coli were present in all strains tested. The most frequent gene was iutA, present in all strains, followed by the genes iucD, csgA, iss2, and irp2. Associations between iron uptake genes, genes related to adhesion, attachment, and serum resistance, as well as genes related to toxin release and bacteriocin, were frequent. The most prevalent phylotype was B1 (40.0%), followed by A (18.5%), D (11.9%), C (9.6%), B2 (7.4%), E (4.4%), F (1.5%), and Clade I (0.7%), with B2 being related to highly virulent traits. The strains presented elevated resistance to antimicrobials such as ciprofloxacin, streptomycin, cephalexin, florfenicol, and ampicillin. More than 90% of the strains were identified as multidrug-resistant, indicating the selection that is induced by the high use of antimicrobials in swine farming.

Ecological modeling, biogeography, and phenotypic analyses setting the tiger cats' hyperdimensional niches reveal a new species.

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.

A Reevaluation of Phylogenomic Data Reveals that Current Understanding in Wheat Blast Population Biology and Epidemiology Is Obfuscated by Oversights in Population Sampling.

Wheat blast, caused by the Pyricularia oryzae Triticum lineage (PoT), first emerged in Brazil and quickly spread to neighboring countries. Its recent appearance in Bangladesh and Zambia highlights a need to understand the disease's population biology and epidemiology so as to mitigate pandemic outbreaks. Current knowledge is mostly based on characterizations of Brazilian wheat blast isolates and comparison with isolates from non-wheat, endemic grasses. These foregoing studies concluded that the wheat blast population lacks host specificity and, as a result, undergoes extensive gene flow with populations infecting non-wheat hosts. Additionally, based on genetic similarity between wheat blast and isolates infecting Urochloa species, it was proposed that the disease originally emerged via a host jump from this grass and that Urochloa likely plays a central role in wheat blast epidemiology owing to its widespread use as a pasture grass. However, due to inconsistencies with broader phylogenetic studies, we suspected that these seminal studies had not actually sampled the populations normally found on endemic grasses and, instead, had repeatedly isolated members of PoT and the related Lolium pathogen lineage (PoL1). Re-analysis of the Brazilian data as part of a comprehensive, global, phylogenomic dataset that included a small number of South American isolates sampled away from wheat confirmed our suspicion and identified four new P. oryzae lineages on grass hosts. As a result, the conclusions underpinning current understanding in wheat blast's evolution, population biology, and epidemiology are unsubstantiated and could be equivocal.

Deep Learning for Size-Agnostic Inverse Design of Random-Network 3D Printed Mechanical Metamaterials.

Practical applications of mechanical metamaterials often involve solving inverse problems aimed at finding microarchitectures that give rise to certain properties. The limited resolution of additive manufacturing techniques often requires solving such inverse problems for specific specimen sizes. Moreover, the candidate microarchitectures should be resistant to fatigue and fracture. Such a multi-objective inverse design problem is formidably difficult to solve but its solution is the key to real-world applications of mechanical metamaterials. Here, a modular approach titled "Deep-DRAM" that combines four decoupled models is proposed, including two deep learning (DL) models, a deep generative model based on conditional variational autoencoders, and direct finite element (FE) simulations. Deep-DRAM integrates these models into a framework capable of finding many solutions to the posed multi-objective inverse design problem based on random-network unit cells. Using an extensive set of simulations as well as experiments performed on 3D printed specimens, it is demonstrate that: 1) the predictions of the DL models are in agreement with FE simulations and experimental observations, 2) an enlarged envelope of achievable elastic properties (e.g., rare combinations of double auxeticity and high stiffness) is realized using the proposed approach, and 3) Deep-DRAM can provide many solutions to the considered multi-objective inverse design problem.

Th-1 cytotoxic cell-mediated response predominates in the tracheal mucosa following Mycoplasma synoviae infection of MS-H-vaccinated chickens.

Mycoplasma synoviae is a pathogen of poultry that causes upper respiratory tract disease. MS-H is a live attenuated temperature-sensitive vaccine that effectively control M. synoviae infection in chickens. However, the mechanisms underpinning protection have not been described previously. In this study, specific-pathogen-free chickens were vaccinated at 3 weeks of age with MS-H vaccine and challenged with field strain M. synoviae 94011/v-18d at 6 weeks of age. Tracheal mucosal inflammation was characterised by the assessment of thickness, histopathological lesions, cellular infiltrates and cytokine transcription. Tracheal lesion scores of unvaccinated-challenged (-V+C) birds were higher than that of vaccinated-challenged (+V+C) birds. +V+C birds displayed early upregulation of IL-4, consistent with a Th-2-skewed response, followed by a later increase in IFN-γ transcription, indicating transition to a Th-1-skewed response. -V+C birds displayed a concurrent early Th-2 and Th-17 response characterised by increase expression of IL-4 and IL-17A respectively, and late T regulatory response characterised by increased IL-10 transcription. +V+C chickens had more cytotoxic T cells (CD8+ T cells) at 7- and 21 days post-challenge (dpc), while -V+C chickens had higher numbers of infiltrating CD4+CD25+ at 7 and 21 dpc. Overall, these observations suggest that the immune response in +V+C chickens had an inflammation characterised by an early Th-2 skewed response followed closely by a Th-1 response and infiltration of cytotoxic T cells, while the response in -V+C chickens was an early Th-2/Th-17-skewed response closely followed by a T regulatory response.

A co-rotational formulation for quasi-steady aerodynamic nonlinear analysis of frame structures.

The design of structures submitted to aerodynamic loads usually requires the development of specific computational models considering fluid-structure interactions. Models using structural frame elements are developed in several relevant applications such as, the design of advanced aircraft wings, wind turbine blades or power transmission lines. In the case of flexible frame structures submitted to fluid flows, the computation of inertial and aerodynamic forces for large displacements and rotations is a challenging task. In this article, we present a novel formulation for the efficient computation of aerodynamic forces in frame structures, coupling the co-rotational framework with the quasi-steady theory. A numerical procedure is provided considering a tangent matrix for the aerodynamic forces. This formulation is implemented in the open-source library ONSAS, allowing users to reproduce the results or solve other frame nonlinear dynamic problems. The proposed formulation and its implementation are validated through the resolution of four numerical examples. The formulation and the numerical procedure proposed efficiently provide accurate solutions for these challenging problems with large displacements and rotations.

Erosion of four Brazilian coastal deltas: how dam construction is changing the natural pattern of coastal sedimentary systems.

Reservoir-building on rivers is still "the Brazilian energy culture", such that many other dams are being constructed and planned, with many other rivers potentially suffering the same impact in their sediment flux. In this study, we evaluated the impacts of reservoir-building on the erosion of the São Francisco, Jequitinhonha, Doce, and Paraíba do Sul river deltas. A time series of Landsat images from 1973 to 2020 was analyzed, with three key highlighted moments (1973, 1997 and 2020) that summarize the erosion processes on these deltas. In addition to the images, continuous river water discharge, sediment discharge and basin rainfall data were analyzed between 1940 and 2020, providing river parameters over a period exceeding that of the satellite data. The findings suggest that coastal erosion has progressed in the four deltas, with higher estimated losses in the São Francisco and Paraíba do Sul over the 47 years of available satellite images. However, despite minimal overall estimated gains, the Jequitinhonha and Doce experienced high erosion at their river mouths, as in the other two rivers, compensated by accretion in distal coastal areas. These results can be explained by reductions in river flux and consequent sediment transport capacity due to reservoirs.

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

High Seroprevalence of Lawsonia intracellularis in Thoroughbred Farms in Southern Brazil.

The aim of the present study was to carry out a serological survey to identify the seroprevalence of Lawsonia intracellularis in six Thoroughbred farms in the Southern region of the state of Rio Grande do Sul, Brazil. During 2019 and 2020, blood samples from 686 Thoroughbred horses were obtained from six different breeding farms. Horses were divided into groups according to age: (1) broodmares (>5 years), (2) two-year-old foals, (3) yearlings, and (4) 0-6 months-old foals. Blood samples were collected by venipuncture of the external jugular vein. The detection of antibodies (IgG) against L. intracellularis was performed by Immunoperoxidase Monolayer Assay. The detection of specific antibodies (IgG) against L. intracellularis in the evaluated population was 51%. The highest detection (86.8%) of IgG was in the broodmares category, while the lowest (5.2%) was in foals of 0-6 months of age. Regarding the farms, the Farm 1 had the highest (67.4%) prevalence of seropositivity against L. intracellularis, while Farm 4 had the lowest (30.6%). There was no record of clinical manifestation of Equine Proliferative Enteropathy in the sampled animals. The results of this study show the high seroprevalence of L. intracellularis in Thoroughbred farms in the Southern of Rio Grande do Sul, suggesting a large and continuous exposure to the agent.

Ethical content in artificial intelligence systems: A demand explained in three critical points.

Artificial intelligence (AI) advancements are changing people's lives in ways never imagined before. We argue that ethics used to be put in perspective by seeing technology as an instrument during the first machine age. However, the second machine age is already a reality, and the changes brought by AI are reshaping how people interact and flourish. That said, ethics must also be analyzed as a requirement in the content. To expose this argument, we bring three critical points - autonomy, right of explanation, and value alignment - to guide the debate of why ethics must be part of the systems, not just in the principles to guide the users. In the end, our discussion leads to a reflection on the redefinition of AI's moral agency. Our distinguishing argument is that ethical questioning must be solved only after giving AI moral agency, even if not at the same human level. For future research, we suggest appreciating new ways of seeing ethics and finding a place for machines, using the inputs of the models we have been using for centuries but adapting to the new reality of the coexistence of artificial intelligence and humans.

A Novel Relapsing Fever Group Borrelia Isolated from Ornithodoros Ticks of the Brazilian Caatinga.

Tick-borne relapsing fever group (RFG) borreliosis remains neglected as a human disease and little is known on its maintenance in ticks and vertebrates, especially in South America. Therefore, this study investigated borrelial infection in Ornithodoros ticks collected in rodent-inhabited rock formations in the Brazilian semiarid region, within the Caatinga biome. Collected ticks (Ornithodoros rietcorreai and Ornithodoros cf. tabajara) were allowed to feed under laboratory conditions on guinea pigs, which had blood samples examined daily by dark-field microscopy. No spirochetes were visualized in the blood of any of four O. rietcorreai-infested guinea pigs. Contrastingly, spirochetes were visualized between 9 and 39 days after tick feeding in the blood of three guinea pigs, each infested with O. cf. tabajara ticks from a different locality. Guinea pig infection was confirmed by passages into experimental animals and by generating DNA sequences of Borrelia spp. from the blood of spirochetemic guinea pigs. Three O. cf. tabajara populations were infected by the same borrelial organism, which was characterized as a novel RFG agent (named as 'Candidatus Borrelia caatinga') based on 10 Borrelia loci (rrs, flaB, glpQ, gyrB, clpX, pepX, pyrG, recG, rplB and uvrA). We demonstrated that O. cf. tabajara is a competent vector of the novel Borrelia sp. isolates, although none of the infected rodents developed clinical illness.

Corneal Perforation associated with "Silent Brain Syndrome" / Perfuração corneana associada à "síndrome do cérebro silencioso"

ABSTRACT This case report describes the clinical characteristics and ophthalmic management of a patient who developed corneal perforation due to severe enophthalmos consistent with "silent brain syndrome." A 27-year-old man with a history of congenital hydrocephalus and ventriculoperitoneal shunt was referred with complaints of "sinking of the eyeballs" and progressively decreasing vision in the left eye. Examination revealed severe bilateral enophthalmos in addition to superonasal corneal perforation with iris prolapse in the left eye. The patient underwent therapeutic keratoplasty the next day. Orbital reconstruction with costochondral graft and shunt revision of the intracranial hypotension were performed the next month to prevent further progression.

RESUMO Este relato de caso descreve as características clínicas e o manejo cirúrgico de um paciente que teve perfuração da córnea devido à enoftalmia grave consistente com a "síndrome do cérebro silencioso". Um homem de 27 anos com história de hidrocefalia congênita e derivação ventrículo-peritoneal foi encaminhado com queixas de "afundamento dos globos oculares" e diminuição progressiva da visão no olho esquerdo. O exame revelou enoftalmo bilateral importante, além de perfuração superonasal da córnea com prolapso iriano no olho esquerdo. A paciente foi submetida à ceratoplastia terapêutica no dia seguinte. Foi realizado no mês seguinte a reconstrução da órbita com enxerto costocondral e revisão do shunt para evitar progressão e piora do caso.

Corneal Perforation associated with "Silent Brain Syndrome".

This case report describes the clinical characteristics and ophthalmic management of a patient who developed corneal perforation due to severe enophthalmos consistent with "silent brain syndrome." A 27-year-old man with a history of congenital hydrocephalus and ventriculoperitoneal shunt was referred with complaints of "sinking of the eyeballs" and progressively decreasing vision in the left eye. Examination revealed severe bilateral enophthalmos in addition to superonasal corneal perforation with iris prolapse in the left eye. The patient underwent therapeutic keratoplasty the next day. Orbital reconstruction with costochondral graft and shunt revision of the intracranial hypotension were performed the next month to prevent further progression.

Actor-Critic Reinforcement Learning Based Algorithm for Contaminant Minimization in sEMG Movement Recognition.

This paper aims to present an approach based on Reinforcement Learning (RL) concept to detect contaminants' type and minimize their effect on surface electromyography signal (sEMG) based movement recognition. The referred method was applied in the pre-processing stage of a sEMG based motion classification system using the Ninapro database 2 artificially contaminated with electrocardiography (ECG) interference, motion artifact (MOA), powerline interference (PLI) and additive white Gaussian noise (WGN). Support Vector Machine was the method for movement classification. The results showed an improvement of 8.9%, 16.7%, 15.9%, 16.5%, and 11.9% in the movement recognition accuracy with the application of the pre-processing algorithm to restore, respectively, one, three, six, nine, and 12 contaminated channels.

Characterization of Traumatic Injuries Due to Motor Vehicle Collisions in Neotropical Wild Mammals.

Motor vehicle collisions (MVCs) are a severe threat to wildlife biodiversity worldwide and most vertebrate species are at risk. However, there is a considerable knowledge gap on the traumatic features and potential patterns of MVCs in wildlife. We investigated traumatic injuries (TIs) caused by MVCs (MVCs-TIs) in 430 neotropical wild mammals representing 44 species from Brazil. Injuries were classified topographically into four categories: abdomen/pelvis (AP), chest (TX), head/neck (HN) and extremities (EX). We also determined the prevalence of pathological changes in MVC fatalities. AP (n = 381; 89%) was the most affected body segment, followed by TX (n = 372; 87%), HN (n = 363; 84%) and EX (n = 288; 67%). The most prevalent gross pathological findings were single or multiple bone fractures (n = 397; 92%), visceral organ rupture (n = 371; 86%), haemothorax (n = 220; 51%) and pulmonary haemorrhage (n = 212; 49%). Microscopically, pulmonary oedema (n = 324; 82%) and haemorrhage (n = 272; 69%) were the most prevalent lesions. No distinct TI patterns were evident across the various taxonomic groups, although trends were found in some taxa, such as armadillos. These results may help clinicians performing emergency care on MVC wildlife patients and may be of value in pathological and forensic investigations where a MVC has been deemed a likely contributory factor to death.