Organoids as a novel tool in modelling infectious diseases.

Infectious diseases worldwide affect human health and have important societal impacts. A better understanding of infectious diseases is urgently needed. In vitro and in vivo infection models have brought notable contributions to the current knowledge of these diseases. Organoids are multicellular culture systems resembling tissue architecture and function, recapitulating many characteristics of human disease and elucidating mechanisms of host-infectious agent interactions in the respiratory and gastrointestinal systems, the central nervous system and the skin. Here, we discuss the applicability of the organoid technology for modeling pathogenesis, host response and features, which can be explored for the development of preventive and therapeutic treatments.

Up-regulation of TNF-alpha/NFkB/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma.

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

CRISPR/Cas9-mediated genome editing of Frankliniella occidentalis, the western flower thrips, via embryonic microinjection.

The western flower thrips, Frankliniella occidentalis, poses a significant challenge in global agriculture as a notorious pest and a vector of economically significant orthotospoviruses. However, the limited availability of genetic tools for F. occidentalis hampers the advancement of functional genomics and the development of innovative pest control strategies. In this study, we present a robust methodology for generating heritable mutations in F. occidentalis using the CRISPR/Cas9 genome editing system. Two eye-colour genes, white (Fo-w) and cinnabar (Fo-cn), frequently used to assess Cas9 function in insects were identified in the F. occidentalis genome and targeted for knockout through embryonic microinjection of Cas9 complexed with Fo-w or Fo-cn specific guide RNAs. Homozygous Fo-w and Fo-cn knockout lines were established by crossing mutant females and males. The Fo-w knockout line revealed an age-dependent modification of eye-colour phenotype. Specifically, while young larvae exhibit orange-coloured eyes, the colour transitions to bright red as they age. Unexpectedly, loss of Fo-w function also altered body colour, with Fo-w mutants having a lighter coloured body than wild type, suggesting a dual role for Fo-w in thrips. In contrast, individuals from the Fo-cn knockout line consistently displayed bright red eyes throughout all life stages. Molecular analyses validated precise editing of both target genes. This study offers a powerful tool to investigate thrips gene function and paves the way for the development of genetic technologies for population suppression and/or population replacement as a means of mitigating virus transmission by this vector.

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

An integrative review of parent education approaches in sport: Considerations for program planning and evaluation.

In recent years, there has been an increase in the delivery and evaluation of parent education programs within youth sport. Subsequently, some recent reviews of these programs have been conducted. However, one consistent issue across many of the programs and associated review papers is the lack of an appropriate evaluation framework to guide the planning or associated reporting of the outcomes of the interventions. This has limited understanding of the overall impact of sport parenting interventions. Thus, the purposes of the current study were as follows: (a) to identify commonalities in the reporting and evaluation of parent education programs; (b) to identify gaps in the reporting and evaluation of parent education programs; (c) to draw these insights together to provide suggestions regarding how the RE-AIM could be used to enhance planning and evaluation of evidence-based programs for parent education in sport. Specifically, utilizing the RE-AIM framework to provide insights into pertinent evaluation metrics, this integrative review aimed to identify commonalities and gaps in the reporting of parent education programs. The RE-AIM framework considers the essential elements to assess the external and internal validity of interventions through five dimensions: Reach, Effectiveness, Adoption, Implementation, and Maintenance (Am J Public Health. 1999;89(9):1322-1327). Subsequently, the review aimed to provide suggestions regarding strategies to enhance the planning and evaluation of evidence-based programs for parent education in sport. Overall, the analysis demonstrated that most studies presented some pertinent evaluation information related to the RE-AIM framework, such as the number of participants and contacts made, the measures used, and the program level. However, the studies also lacked information on participant exclusion criteria, the method used to select the delivery agent (e.g., parents engaged in the program), and cost measures. Overall, the current study identified various areas where programs could be enhanced, specifically related to reporting procedural elements (e.g., program design, target population, and costs) pertaining to the implementation of parent education programs.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Anti-Protozoan Activities of Polar Fish-Derived Polyalanine Synthetic Peptides.

Chagas disease, sleeping sickness and malaria are infectious diseases caused by protozoan parasites that kill millions of people worldwide. Here, we performed in vitro assays of Pa-MAP, Pa-MAP1.9, and Pa-MAP2 synthetic polyalanine peptides derived from the polar fish Pleuronectes americanus toward Trypanosoma cruzi, T. brucei gambiense and Plasmodium falciparum activities. We demonstrated that the peptides Pa-MAP1.9 and Pa-MAP2 were effective to inhibit T. brucei growth. In addition, structural analyses using molecular dynamics (MD) studies showed that Pa-MAP2 penetrates deeper into the membrane and interacts more with phospholipids than Pa-MAP1.9, corroborating the previous in vitro results showing that Pa-MAP1.9 acts within the cell, while Pa-MAP2 acts via membrane lysis. In conclusion, polyalanine Pa-MAP1.9 and Pa-MAP2 presented activity against bloodstream forms of T. b. gambiense, thus encouraging further studies on the application of these peptides as a treatment for sleeping sickness.

Improving accuracy of early dental carious lesions detection using deep learning-based automated method.

OBJECTIVE: To investigate the effectiveness of a convolutional neural network (CNN) in detecting healthy teeth and early carious lesions on occlusal surfaces and to assess the applicability of this deep learning algorithm as an auxiliary aid. MATERIALS AND METHODS: A total of 2,481 posterior teeth (2,459 permanent and 22 deciduous teeth) with varying stages of carious lesions were classified according to the International Caries Detection and Assessment System (ICDAS). After clinical evaluation, ICDAS 0 and 2 occlusal surfaces were photographed with a professional digital camera. VGG-19 was chosen as the CNN and the findings were compared with those of a reference examiner to evaluate its detection efficiency. To verify the effectiveness of the CNN as an auxiliary detection aid, three examiners (an undergraduate student (US), a newly graduated dental surgeon (ND), and a specialist in pediatric dentistry (SP) assessed the acquired images (Phase I). In Phase II, the examiners reassessed the same images using the CNN-generated algorithms. RESULTS: The training dataset consisted of 8,749 images, whereas the test dataset included 140 images. VGG-19 achieved an accuracy of 0.879, positive agreement of 0.827, precision of 0.949, negative agreement 0.800, and an F1-score of 0.887. In Phase I, the accuracy rates for examiners US, ND, and SP were 0.543, 0.771, and 0.807, respectively. In Phase II, the accuracy rates improved to 0.679, 0.886, and 0.857 for the respective examiners. The number of correct answers was significantly higher in Phase II than in Phase I for all examiners (McNemar test;P<0.05). CONCLUSIONS: VGG-19 demonstrated satisfactory performance in the detection of early carious lesions, as well as an auxiliary detection aid. CLINICAL RELEVANCE: Automated detection using deep learning algorithms is an important aid in detecting early caries lesions and improves the accuracy of the disease detection, enabling quicker and more reliable clinical decision-making.

A conceptual model to establish preventive and corrective actions to guarantee water safety following scenarios of tailing dam failure.

One of the impacts related to mining dam failures is the change in water quality downstream of the rupture and a knowledge gap is observed in terms of methodologies aimed at the prognosis of impact in water abstractions, a vulnerability that can be identified before a rupture event. Thus, the present work aims to describe a novel methodological proposal, not currently considered by control agencies, of a standard protocol that enables a comprehensive prognosis of the impacts on water quality impact in scenarios of dam failure. Initially, extensive bibliographic research was carried out on the main disruptions events since 1965 intended to better comprehend the impacts on water quality and to identify mitigatory actions proposed by the time. The information provided a framework to propose a conceptual model for the prognosis of water abstractions, with the suggestion of software and studies to comprehend the different scenarios in the event of dam failure. A protocol was prepared to obtain information on potentially affected inhabitants and a multicriteria analysis was developed using the Geographic Information System (GIS) to suggest the employment of preventive and corrective actions. The methodology was demonstrated in the Velhas River basin considering a hypothetical scenario of tailing dam failure. Changes in water quality would be observed in 274 km of its extension, mainly related to alterations in solids, metals, and metalloids' concentration, in addition to the impact on important water treatment plants. The map algebra and the results suggest the need for structuring actions in cases where the water abstraction is intended for human supply and in populations greater than 100,000 inhabitants. Populations smaller than these, or usages other than human supply, could be supplied by water tank trucks or mixed alternatives. The methodology pointed out the necessity for structuring supply actions with due notice, with the potential to prevent water shortages in scenarios of tailing dam failure and to complement the enterprise resource planning of mining companies.

Dihydroeugenol derivatives associated with blue LED light: A different form to face multidrug resistant (MDR) bacteria.

Eugenol has already had its pharmacological properties elucidated in previous studies, including antibacterial and antifungal properties. Based on such information, this study aimed to evaluate the antibacterial and modulatory activity of coumarin compounds prepared from dihydroeugenol and to associate them with blue LED light for the same activity. For this study, five of the substances available: compound 1 (C1), 8-methoxy-2-oxo-6-propyl-2H-chromen-3-carboxylic acid, compound (C2), 3-(hydroxy(4-nitrophenyl)methyl)-8- methoxy-6-propyl-2H-chromen-2-one, compound 7 (C3), 8-hydroxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one, compound 8 (C4), 3-(4-aminobenzoyl)-8-methoxy-6-propyl-2H-chromen-2-one and Compound 9 (C5), 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one 2-one. To determine the MIC, the broth microdilution technique was used. The products were evaluated for their potential to modulate the activity of antibiotics. Afterward, the plates were submitted to blue LED light for 20 min. When exposed to LED, C3 exhibited a decrease in MIC for SA ATCC and C5 for EC ATCC, with an average of 645.08 µg/mL for both cases. C2 and C4 exhibited synergism in a greater number of situations. However, C3 showed promising activity against S. aureus. C1 and C2 already acted better against E. coli, with the difference that C1 acted better against these bacteria when associated with LED. In general, the compounds studied here exhibited good antibacterial activity when associated with LED.

An overview of the molecular and physiological antidepressant mechanisms of physical exercise in animal models of depression.

BACKGROUND: Depression is a global disease that affects the physical and mental health of people of all ages. Non-pharmacological and unconventional methods of treatment, such as regular physical exercise, have been recommended to treat depression. METHODS: Here, we briefly review the literature about the physiological and molecular mechanisms of exercise antidepressants in depressive-like behavior in animal models of depression. RESULTS: The main hysiological and molecular mechanisms of physical exercise in depression include blood flow changes in several areas of the brain, increase in brain serotonin synthesis, increase in antioxidant enzymes, increase in serum and brain brain-derived neuro factor (BDNF) levels, decrease in cortisol levels and reduced inflammation in peripheral and brain tissues. Physical exercise also leads to increased activation of the phosphatidylinositol-3-kinase (PI3K), PGC-1α/FNDC5/Irisin pathway, BDNF concentrations (serum and cerebral), extracellular signal-regulated kinase and cAMP-response element binding protein (mainly in neurons of the hippocampus and prefrontal cortex), which together contribute to fight or inhibit the development of depression symptoms. These molecular and physiological mechanisms work in synchrony, further enhancing their effects. CONCLUSION: Physical exercise can be used as a safe and effective non-pharmacological treatment in depression.

Doppler Shift Tolerance of Typical Pseudorandom Binary Sequences in PMCW Radar.

In the context of all-digital radar systems, phase-modulated continuous wave (PMCW) based on pseudorandom binary sequences (PRBSs) appears to be a prominent candidate modulation scheme for applications such as autonomous driving. Among the reasons for its candidacy are its simplified transmitter architecture and lower linearity requirements (e.g., compared to orthogonal-frequency division multiplexing radars), as well as its high velocity unambiguity and multiple-input multiple-output operation capability, all of which are characteristic of digital radars. For appropriate operation of a PMCW radar, choosing a PRBS whose periodic autocorrelation function (PACF) has low sidelobes and high robustness to Doppler shifts is paramount. In this sense, this article performs an analysis of Doppler shift tolerance of the PACFs of typically adopted PRBSs in PMCW radar systems supported by simulation and measurement results. To accurately measure the Doppler-shift-induced degradation of PACFs, peak power loss ratio (PPLR), peak sidelobe level ratio (PSLR), and integrated-sidelobe level ratio (ISLR) were used as metrics. Furthermore, to account for effects on targets whose ranges are not multiples of the range resolution, oversampled PACFs are analyzed.

Growth performance and rumen morphometrics of Nellore and ½ Angus/Nellore feedlot cattle adapted over 9 and 14 days to high-concentrate diets.

The objective of this study was to evaluate the effects of adapting Nellore and ½ Angus/Nellore (AN) feedlot cattle over periods of 9 and 14 days to high-concentrate diets on performance, feeding behaviour, carcass traits and rumen morphometrics. Seventy-two yearling bulls (313.5 kg ± 24.5), 36 Nellore and 36 AN, were randomly allocated in 24 pens (3 animals/pen; 24 m2 and 2.0 m of bunk space/animal) according to a randomized complete block design with a 2 × 2 factorial arrangement of treatments as follows: Nellore adapted for 9 days, Nellore adapted for 14 days, AN adapted for 9 days, and AN adapted for 14 days. Each treatment was composed by 6 pens (considered the experimental unit in this study). The adaptation lasted either 9 or 14 days and consisted of 3 step-up diets. Therefore, yearling bulls received the finishing diet containing 86% concentrate either on day 10 or 15 of the study, which lasted 89 days taking into account adaptation and finishing periods. Cattle were slaughtered in a commercial abattoir, and two 1-cm2 -rumen fragments, one from cranial and another from ventral sac, were collected. The AN cattle outperformed Nellore in terms of average daily gain (1.71 kg/day vs. 1.27 kg/day, p < 0.01), gain:feed ratio (0.137 kg/kg vs. 0.127 kg/kg, p = 0.02) and hot carcass weight (243.64 kg vs. 228.98 kg, p < 0.01). No main effect of the adaptation period was observed for any of the feedlot performance and carcass traits variables evaluated. Compared to feedlot cattle adapted for 9 days, feedlot cattle adapted for 14 days sorted against long (0.68 vs. 0.91, p < 0.01) and for fine particles (1.04 vs. 1.00, p = 0.01). An interaction (p < 0.01) of genotype and adaptation period was observed for rumenitis, where Nellore bulls adapted for 14 days presented the highest scores. In conclusion, there was no evidence that either Nellore or AN cattle benefit from an adaptation period shorter than 14 days.

Reenacting the Birth of a Function: Functional Divergence of HIUases and Transthyretins as Inferred by Evolutionary and Biophysical Studies.

Transthyretin was discovered in the 1940s, named after its ability to bind thyroid hormones and retinol. In the genomic era, transthyretins were found to be part of a larger family with homologs of no obvious function, then called transthyretin-related proteins. Thus, it was proposed that the transthyretin gene could be the result of gene duplication of an ancestral of this newly identified homolog, later found out to be an enzyme involved in uric acid degradation, then named HIUase (5-hydroxy-isourate hydrolase). Here, we sought to re-enact the evolutionary history of this protein family by reconstructing, from a phylogeny inferred from 123 vertebrate sequences, three ancestors corresponding to key moments in their evolution-before duplication; the common transthyretin ancestor after gene duplication and the common ancestor of Eutheria transthyretins. Experimental and computational characterization showed the reconstructed ancestor before duplication was unable to bind thyroxine and likely presented the modern HIUase reaction mechanism, while the substitutions after duplication prevented that activity and were enough to provide stable thyroxine binding, as confirmed by calorimetry and x-ray diffraction. The Eutheria transthyretin ancestor was less prone to characterization, but limited data suggested thyroxine binding as expected. Sequence/structure analysis suggests an early ability to bind the Retinol Binding Protein. We solved the X-ray structures from the two first ancestors, the first at 1.46 resolution, the second at 1.55 resolution with well-defined electron density for thyroxine, providing a useful tool for the understanding of structural adaptation from enzyme to hormone distributor.

A new natural detector for irradiations with blue LED light source in photodynamic therapy measurements via UV-Vis spectroscopy.

Photodynamic therapy has been recently studied, bringing innovations regarding the reduction of exposure time to light by the patient. This work aimed to investigate the feasibility of using Coutarea hexandra (Jacq.) K. Schum (CHS) as a detector in photodynamic therapy measurements. For this, an irradiator containing a blue LED bulb lamp was utilized. The CHS samples were irradiated with ten doses from 0.60 up to 6.0 kJ/cm2, and six concentrations were prepared (1, 2, 3, 4, 5, and 6 mg/ml) for the CHS detector samples. After irradiation, the detector samples were evaluated using UV-Vis spectrophotometry. The results showed the behavior of the CHS detector with doses and concentrations, its sensitivity, and its linearity was also evaluated both by Wavelength Method (WM) and the Kernel Principal Component Regression (KPCR) Statistical Method. The values obtained indicate that this method can be applied to the CHS sample detector. In conclusion, the CHS is a promising detector in the field of photodynamic therapy.

Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.

Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60 min per session, 3 times per week, for 24 weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.

Characterization of a novel alphabaculovirus isolated from the Southern armyworm, Spodoptera eridania (Cramer, 1782) (Lepidoptera: Noctuidae) and the evolution of odv-e66, a bacterium-acquired baculoviral chondroitinase gene.

The Southern armyworm Spodoptera eridania (Lepidoptera: Noctuidae) is native to the American tropics and a polyphagous pest of several crops. Here we characterized a novel alphabaculovirus isolated from S. eridania, isolate Spodoptera eridania nucleopolyhedrivurus CNPSo-165 (SperNPV-CNPSo-165). SperNPV-CNPSo-165 occlusion bodies were found to be polyhedral and to contain virions with multiple nucleocapsids. The virus was lethal to S. eridania and S. albula but not to S. frugiperda. The SperNPV-CNPSo-165 genome was 137.373 bp in size with a G + C content of 42.8%. We annotated 151 ORFs with 16 ORFs unique among baculoviruses. Phylogenetic inference indicated that this virus was closely related to the most recent common ancestor of other Spodoptera-isolated viruses.

Limb ischemia in patients with COVID-19.

This narrative review covers the life-threatening thromboembolic events associated with SARS-CoV-2 infection/COVID-19. It addresses the physical changes that cause vascular and arterial damage to limbs, laboratory management of coagulation, and management of anticoagulation. COVID-19's relationship with deep venous thrombosis and arterial thrombosis is also emphasized. The main thromboembolic events described in the literature are illustrated with examples from our experience with COVID-19 patients.

Esta revisão narrativa abrange os eventos tromboembólicos com risco de vida associados a infecção por SARS-CoV-2/COVID-19. Aborda as mudanças físicas que causam danos vasculares e arteriais aos membros, o manejo laboratorial da coagulação e o manejo da anticoagulação. A relação de COVID-19 com trombose venosa profunda e trombose arterial também é enfatizada. Os principais eventos tromboembólicos descritos na literatura são ilustrados a partir de nossa experiência com pacientes COVID-19.

A new method bridging graph theory and residue co-evolutionary networks for specificity determinant positions detection.

MOTIVATION: Computational studies of molecular evolution are usually performed from a multiple alignment of homologous sequences, on which sequences resulting from a common ancestor are aligned so that equivalent residues are placed in the same position. Residues frequency patterns of a full alignment or from a subset of its sequences can be highly useful for suggesting positions under selection. Most methods mapping co-evolving or specificity determinant sites are focused on positions, however, they do not consider the case for residues that are specificity determinants in one subclass, but variable in others. In addition, many methods are impractical for very large alignments, such as those obtained from Pfam, or require a priori information of the subclasses to be analyzed. RESULTS: In this paper we apply the complex networks theory, widely used to analyze co-affiliation systems in the social and ecological contexts, to map groups of functional related residues. This methodology was initially evaluated in simulated environments and then applied to four different protein families datasets, in which several specificity determinant sets and functional motifs were successfully detected. AVAILABILITY AND IMPLEMENTATION: The algorithms and datasets used in the development of this project are available on http://www.biocomp.icb.ufmg.br/biocomp/software-and-databases/networkstats/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Coevolved Positions Represent Key Functional Properties in the Trypsin-Like Serine Proteases Protein Family.

Trypsin-like serine proteases are a group of homologous enzymes which exert multiple roles in both vertebrate and invertebrate organisms. Key properties of these enzymes include their activation from an inactive zymogen form to their active form by cleavage of residues in their N-terminus, the presence of a conserved catalytic triad of residues, and the existence of different patterns of substrate selectivity for residue cleavage between the various members of this protein family. In this article, we apply the decomposition of residue coevolution networks computational method to find sets of residues related to some of these key properties, especially to zymogen activation. Positive selection detection, normal modes analysis, and the calculation of thermal couplings between the bovine trypsinogen and bovine trypsin structures residues yielded further information for understanding the zymogen activation process and highlighted the importance of some of the coevolved set residues during these transitions.