AmpClass: an Antimicrobial Peptide Predictor Based on Supervised Machine Learning.

In the last decades, antibiotic resistance has been considered a severe problem worldwide. Antimicrobial peptides (AMPs) are molecules that have shown potential for the development of new drugs against antibiotic-resistant bacteria. Nowadays, medicinal drug researchers use supervised learning methods to screen new peptides with antimicrobial potency to save time and resources. In this work, we consolidate a database with 15945 AMPs and 12535 non-AMPs taken as the base to train a pool of supervised learning models to recognize peptides with antimicrobial activity. Results show that the proposed tool (AmpClass) outperforms classical state-of-the-art prediction models and achieves similar results compared with deep learning models.

Ratio changes in blood-feeding and voltinism in black flies (Diptera: Simuliidae) over a latitudinal gradient in North America north of Mexico.

We explored how the ratio of blood-feeding behaviour-nonfeeding, bird feeding (ornithophily) and mammal feeding (mammalophily)-and voltinism (univoltine and multivoltine) vary over a latitudinal gradient from Alaska to Florida. These two fixed species traits were divided into five mutually exclusive combinations of trait states-nonfeeding/univoltine, ornithophilic/univoltine, mammalophilic/univoltine, ornithophilic/multivoltine and mammalophilic/multivoltine-within each of three datasets (north, east and west). We found a significant association between location (north, east and west) and trait state, which was driven by the large percentage of nonfeeding females in the north. When this trait state was removed, no significant differences were found for the remaining trait states and locations. Although the distribution of trait states did not differ between east and west datasets, the distribution with relation to 1° changes in latitude within each of these datasets showed distinct differences. In the east, both ornithophilic/univoltine and mammalophilic/univoltine species significantly increased with latitude, in proportion to the total species present. In contrast, the proportion of mammalophilic/multivoltine species decreased as latitude increased. Ornithophilic/multivoltine species in the east and the trait states in the west did not show any significant relationship to latitude.

Case Report: Disseminated Histoplasmosis of the Tongue Presenting Decades after Exposure in Latin America.

Histoplasma capsulatum is a thermally dimorphic fungal pathogen endemic to the Mississippi and Ohio River Valley regions of North America and much of Central and South America. As an opportunistic pathogen, H. capsulatum can assume a latent infection that can be reactivated by immunocompromised states or immunosuppressive therapy. We report a case of a 72-year-old man who lived in rural regions of Panama, Honduras, and Nicaragua while serving in the U.S. military from 1987 to 1991. Three decades after his initial exposure, the patient presented for evaluation of a painful tongue ulcer that originated when he began taking adalimumab to manage his psoriatic arthritis 2 years earlier. Tissue scraping of the tongue ulcer grew a whitish to cream-colored, fluffy-textured mold that was morphologically identified as Histoplasma. Molecular analysis of the fungus confirmed H. capsulatum var. Latin American group A, known as Histoplasma suramericanum. Further testing showed a positive H. capsulatum antibody mycelial complement fixation, and a 1-cm calcified nodule in the lower lobe of the left lung on computed tomography. Here, we highlight the importance of recognizing disseminated histoplasmosis in patients with exposure to endemic regions before initiating immunosuppressive therapy.

OnionFoliageSET: Labeled dataset for small onion and foliage flower crop detection.

Digital image datasets for Precision Agriculture (PA) still need to be available. Many problems in this field of science have been studied to find solutions, such as detecting weeds, counting fruits and trees, and detecting diseases and pests, among others. One of the main fields of research in PA is detecting different crop types with aerial images. Crop detection is vital in PA to establish crop inventories, planting areas, and crop yields and to have information available for food markets and public entities that provide technical help to small farmers. This work proposes public access to a digital image dataset for detecting green onion and foliage flower crops located in the rural area of Medellín City - Colombia. This dataset consists of 245 images with their respective labels: green onion (Allium fistulosum), foliage flowers (Solidago Canadensis and Aster divaricatus), and non-crop areas prepared for planting. A total of 4315 instances were obtained, which were divided into subsets for training, validation, and testing. The classes in the images were labeled with the polygon method, which allows training machine learning algorithms for detection using bounding boxes or segmentation in the COCO format.

TRIM32 inhibits Venezuelan Equine Encephalitis Virus Infection by targeting a late step in viral entry.

Alphaviruses are mosquito borne RNA viruses that are a reemerging public health threat. Alphaviruses have a broad host range, and can cause diverse disease outcomes like arthritis, and encephalitis. The host ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but the molecular mechanisms remain poorly characterized. In addition, whether certain E3 ubiquitin ligases or deubiquitinases act as alphavirus restriction factors remains poorly understood. Here, we employed a cDNA expression screen to identify E3 ubiquitin ligase TRIM32 as a novel intrinsic restriction factor against alphavirus infection, including VEEV-TC83, SINV, and ONNV. Ectopic expression of TRIM32 reduces alphavirus infection, whereas depletion of TRIM32 with CRISPR-Cas9 increases infection. We demonstrate that TRIM32 inhibits alphaviruses through a mechanism that is independent of the TRIM32-STING-IFN axis. Combining reverse genetics and biochemical assays, we found that TRIM32 interferes with genome translation after membrane fusion, prior to replication of the incoming viral genome. Furthermore, our data indicate that the monoubiquitination of TRIM32 is important for its antiviral activity. Notably, we also show two TRIM32 pathogenic mutants R394H and D487N, related to Limb-girdle muscular dystrophy (LGMD), have a loss of antiviral activity against VEEV-TC83. Collectively, these results reveal that TRIM32 acts as a novel intrinsic restriction factor suppressing alphavirus infection and provides insights into the interaction between alphaviruses and the host UPS.

CYCLOPS: A cyclists' orientation data acquisition system using RGB camera and inertial measurement units (IMU).

This paper introduces CYCLOPS, an acquisition system developed to capture images and inertial measurement data of moving cyclists from a vehicle. The development of CYCLOPS addresses the need to acquire useful data for training machine learning models capable of predicting the motion intentions of cyclists on urban roads. Considering its application, it is a completely original development. The system consists of two devices. The first device is installed on the bicycle and is based on an electronic acquisition board comprising an inertial measurement unit (IMU), a microcontroller, and a transceiver for sending the cyclist's acceleration and orientation data to a vehicle. The second device is installed on the vehicle and uses the same board architecture to acquire the vehicle's accelerations and orientations, along with an RGB monocular camera. The data is stored in real-time in a laptop's drive for subsequent analysis and manipulation. The hardware architecture is presented in detail, including the designs to install the devices, for IMUs configuration, and software installation on the laptop. All design and software files required to develop the proposed system are available for download at: doi.org/10.17632/3yx5y8b7tm.1, licensed under the Open-source license CC BY 4.0.

Transition between peritoneal dialysis modalities: Impact on blood pressure levels and drug prescription in a national multicentric cohort.

BACKGROUND: Hypertension is a leading cause of kidney failure, affects most dialysis patients and associates with adverse outcomes. Hypertension can be difficult to control with dialysis modalities having differential effects on sodium and water removal. There are two main types of peritoneal dialysis (PD), automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). It is unknown whether one is superior to the other in controlling blood pressure (BP). Therefore, the aim of our study was to analyse the impact of switching between these two PD modalities on BP levels in a nationally representative cohort. METHODS: This was a cohort study of patients on PD from 122 dialysis centres in Brazil (BRAZPD II study). Clinical and laboratory data were collected monthly throughout the study duration. We selected all patients who remained on PD at least 6 months and 3 months on each modality at minimum. We compared the changes in mean systolic/diastolic blood pressures (SBP/DBP) before and after modality transition using a multilevel mixed-model where patients were at first level and their clinics at the second level. RESULTS: We analysed data of 848 patients (814 starting on CAPD and 34 starting on APD). The SBP decreased by 4 (SD 22) mmHg when transitioning from CAPD to APD (p < 0.001) and increased by 4 (SD 21) mmHg when transitioning from APD to CAPD (p = 0.38); consistent findings were seen for DBP. There was no significant change in the number of antihypertensive drugs prescribed before and after transition. CONCLUSIONS: Transition between PD modalities seems to directly impact on BP levels. Further studies are needed to confirm if switching to APD could be an effective treatment for uncontrolled hypertension among CAPD patients.

Antimicrobial peptides designed by computational analysis of proteomes.

Antimicrobial peptides (AMPs) are promising cationic and amphipathic molecules to fight antibiotic resistance. To search for novel AMPs, we applied a computational strategy to identify peptide sequences within the organisms' proteome, including in-house developed software and artificial intelligence tools. After analyzing 150.450 proteins from eight proteomes of bacteria, plants, a protist, and a nematode, nine peptides were selected and modified to increase their antimicrobial potential. The 18 resulting peptides were validated by bioassays with four pathogenic bacterial species, one yeast species, and two cancer cell-lines. Fourteen of the 18 tested peptides were antimicrobial, with minimum inhibitory concentrations (MICs) values under 10 µM against at least three bacterial species; seven were active against Candida albicans with MICs values under 10 µM; six had a therapeutic index above 20; two peptides were active against A549 cells, and eight were active against MCF-7 cells under 30 µM. This study's most active antimicrobial peptides damage the bacterial cell membrane, including grooves, dents, membrane wrinkling, cell destruction, and leakage of cytoplasmic material. The results confirm that the proposed approach, which uses bioinformatic tools and rational modifications, is highly efficient and allows the discovery, with high accuracy, of potent AMPs encrypted in proteins.

Molecular characterization and demographic insights into soybean bud borer (Lepidoptera: Tortricidae) in Brazil.

The soybean bud borer, a soybean pest in Brazil, was initially identified as Crocidosema aporema (Walsingham 1914) (Lepidoptera: Tortricidae). Outbreaks of this species have recently increased, but identification of this pest remains uncertain, and the historical factors associated with its geographic distribution in Brazil are little known. Here, we conducted a species characterization and phylogeographic analysis based on molecular and morphological evidence. Ninety individuals of bud-borers Lepidoptera were collected in different regions of Brazil. We sequenced COI and COII mitochondrial genes and examined wing patterns and male genital morphology. DNA barcoding approach revealed that 10 individuals were Argyrotaenia sphaleropa (Meyrick 1909) (Lepidoptera: Tortricidae) and 80 were a species of the genus Crocidosema Zeller. The morphology of the adult genitalia and wings proved to be insufficient to confirm the identification of Brazilian individuals as C. aporema, a species originally described from a high-elevation site in Costa Rica. Furthermore, the genetic distance between putative C. aporema specimens from Brazil and Costa Rica (ranging from 5.2% to 6.4%) supports the hypothesis that the Brazilian specimens are not referable to C. aporema. Our analysis revealed a single genetic strain (i.e., species) with low genetic diversity on soybean crops. We found no indication that the genetic structure was related to geographic distance among populations or edaphoclimatic regions. The population expansion of the soybean bud borer coincides with the increase in the area of soybean production in Brazil, suggesting that expanded soybean farming has allowed a significant increase in the effective population size of this pest.

Two new species of the hyperdiverse geometrid moth genus Eois (Lepidoptera, Geometridae, Larentiinae) from Ecuador, with descriptions of early stages.

The hyperdiverse geometrid genus Eois Hübner, estimated to encompass more than 1,000 species, is among the most species-rich genera in all of Lepidoptera. While the genus has attracted considerable attention from ecologists and evolutionary biologists in recent decades, limited progress has been made on its alpha taxonomy. This contribution focuses on the Olivacea clade, whose monophyly has been recognized previously through molecular analyses. We attempt to define the clade from a morphological perspective and recognize the following species based on morphology and genomic data: E.olivacea (Felder & Rogenhofer); E.pseudolivacea Doan, sp. nov.; E.auruda (Dognin), stat. rev.; E.beebei (Fletcher, 1952), stat. rev.; E.boliviensis (Dognin), stat. rev.; and E.parumsimii Doan, sp. nov. Descriptions and illustrations of the immature stages of E.pseudolivacea reared from Piper (Piperaceae) in Ecuador are provided.

Racial Inequities in the Control of Hypertension and the Explanatory Role of Residential Segregation: a Decomposition Analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The mechanisms underlying racial inequities in uncontrolled hypertension have been limited to individual factors. We investigated racial inequities in uncontrolled hypertension and the explanatory role of economic segregation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). All 3897 baseline participants with hypertension (2008-2010) were included. Uncontrolled hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg), self-reported race (White/Brown/Black people), and neighborhood economic segregation (low/medium/high) were analyzed cross-sectionally. We used decomposition analysis, which describes how much a disparity would change (disparity reduction; explained portion) and remain (disparity residual; unexplained portion) upon removing racial differences in economic segregation (i.e., if Black people had the distribution of segregation of White people, how much we would expect uncontrolled hypertension to decrease among Black people). Age- and gender-adjusted prevalence of uncontrolled hypertension (39.0%, 52.6%, and 54.2% for White, Brown, and Black participants, respectively) remained higher for Black and Brown vs White participants, regardless of economic segregation. Uncontrolled hypertension showed a dose-response pattern with increasing segregation levels for White but not for Black and Brown participants. After adjusting for age, gender, education, and study center, unexplained portion (disparity residual) of race on uncontrolled hypertension was 18.2% (95% CI 13.4%; 22.9%) for Black vs White participants and 12.6% (8.2%; 17.1%) for Brown vs White participants. However, explained portion (disparity reduction) through economic segregation was - 2.1% (- 5.1%; 1.3%) for Black vs White and 0.5% (- 1.7%; 2.8%) for Brown vs White participants. Although uncontrolled hypertension was greater for Black and Brown vs White people, racial inequities in uncontrolled hypertension were not explained by economic segregation.

Megakaryocyte-induced contraction of plasma clots: cellular mechanisms and structural mechanobiology.

ABSTRACT: Nonmuscle cell contractility is an essential feature underlying diverse cellular processes such as motility, morphogenesis, division and genome replication, intracellular transport, and secretion. Blood clot contraction is a well-studied process driven by contracting platelets. Megakaryocytes (MKs), which are the precursors to platelets, can be found in bone marrow and lungs. Although they express many of the same proteins and structures found in platelets, little is known about their ability to engage with extracellular proteins such as fibrin and contract. Here, we have measured the ability of MKs to compress plasma clots. Megakaryocytes derived from human induced pluripotent stem cells (iPSCs) were suspended in human platelet-free blood plasma and stimulated with thrombin. Using real-time macroscale optical tracking, confocal microscopy, and biomechanical measurements, we found that activated iPSC-derived MKs (iMKs) caused macroscopic volumetric clot shrinkage, as well as densification and stiffening of the fibrin network via fibrin-attached plasma membrane protrusions undergoing extension-retraction cycles that cause shortening and bending of fibrin fibers. Contraction induced by iMKs involved 2 kinetic phases with distinct rates and durations. It was suppressed by inhibitors of nonmuscle myosin IIA, actin polymerization, and integrin αIIbß3-fibrin interactions, indicating that the molecular mechanisms of iMK contractility were similar or identical to those in activated platelets. Our findings provide new insights into MK biomechanics and suggest that iMKs can be used as a model system to study platelet contractility. Physiologically, the ability of MKs to contract plasma clots may play a role in the mechanical remodeling of intravascular blood clots and thrombi.

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.

Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. In particular, the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineered human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DDR, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, we find neither evidence that HR causes extension of telomeres beyond their initial lengths, nor an apparent role for ZSCAN4 in this process. Rather, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage.

Characterization of the flanking region of the Shiga toxin operon in Stx2a bacteriophages reveals a diversity of the NanS-p sialate O-acetylesterase gene.

Shiga toxin-producing E. coli (STEC) are diarrheagenic strains that can cause bloody diarrhea and hemolytic-uremic syndrome. Their main virulence factor, the Shiga toxin (Stx), is encoded by phages integrated into the bacterial chromosome. Stx phages are widely diverse and carry many genes with limited or unknown function. As the toxin subtype Stx2a is associated with highly pathogenic strains, this study was mainly focused on the characterization of the stx flanking region of Stx2a phages. Of particular interest was a sialate O-acetylesterase (NanS-p), which has been described previously to be encoded downstream stx in some phage genomes and may confer a growth advantage for STEC. Complete DNA sequences of Stx2a phages and prophages were retrieved from the GenBank database, and the genomic regions from anti-terminator Q to holin S genes were bioinformatically analyzed. Predicted NanSp sequences from phages encoding other Stx subtypes were also studied. Additionally, expression of nanS-p was quantified by qPCR in strains selected from our laboratory collection. The analysis of Stx2a phage genomes showed that all carried the Q, stx2a, nanS-p and S genes, but with allele diversity and other sequence differences. In particular, sequence differences were detected in each of the three domains of NanS-p esterases encoded by Stx2a phages and other Stx phages; however, nanS-p was not identified in the Stx2e, Stx2f and Stx2g phages analyzed. The expression of nanS-p increased in most stx2a-positive strains under phage inducing conditions, as was previously shown for stx2a. As the present work showed diversity at the Q-S region among Stx phages, and particularly in the encoded NanS-p enzyme, future studies will be necessary to evaluate if NanS-p variants differ in their activity and to assess the impact of the absence of nanS-p in certain Stx phages.

Short-term effects of a high-severity summer wildfire on conifer forest moth (Lepidoptera) communities in New Mexico, USA.

Forest fires in North America are becoming larger in area and burning with higher severity as a result of climate change and land management practices. High-severity, stand-replacement fires can inflict major changes to forest insect communities, potentially extirpating many species through altered post-fire habitat resources. We assessed forest-dwelling macrolepidopteran moth communities in mixed conifer and ponderosa pine forests during the first year after the 2011 Las Conchas fire in New Mexico, USA. We deployed blacklight traps in replicated burned and unburned stands during June, July, and August in 2012. We collected 9,478 individuals, representing 211 species and 8 families. Noctuidae (124 species) and Geometridae (53) comprised the majority of the taxa, followed by Erebidae (21), Sphingidae (5), Notodontidae (3), Lasiocampidae (2), Saturniidae (2), and Drepanidae (1). Moth communities (species composition and abundances) in each forest type (mixed conifer vs. ponderosa pine) were statistically distinguishable, but shared 56.4% (119) of observed species. Overall, compared to unburned forests, post-fire moth communities in both forest types had significantly lower numbers of individuals, species richness and diversity, and lower evenness in ponderosa pine forests. As expected, categorizing moth taxa by larval host plant taxa revealed that reductions of moth populations following fire were associated with the elimination or reduction of available larval host plants (particularly conifers, oaks, and junipers). We predict that future moth community succession will likely parallel the overall transformation from a forested landscape to a montane meadow/grassland ecosystem, with continued reduction in tree-feeding species and increasing dominance by forb/grass-feeding species.

Total events and net clinical benefit of rivaroxaban and aspirin in patients with chronic coronary or peripheral artery disease: the COMPASS trial

BACKGROUND: Low dose rivaroxaban with aspirin reduced major cardiovascular events (MACE) compared to aspirin alone in patients with cardiovascular disease although effects on total events are unknown. METHODS: The COMPASS clinical trial randomized 27,395 participants with chronic coronary and/or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg daily. We analyzed total (first and recurrent) MACE outcomes of cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome of major bleeding. Exploratory analyses included on-treatment and net clinical benefit. Total MACE and safety events were modeled for each treatment. RESULTS: MACE events were lowest in rivaroxaban with aspirin (379 first MACE, 432 total MACE) compared with rivaroxaban (448 first, 508 total) or aspirin alone (496 first, 574 total). Rivaroxaban and aspirin reduced total MACE events compared with aspirin alone [HR 0.75, 95% CI 0.66-0.85, P < .0001, number needed to treat for 2 years (NNT2y) of 63]. Total major bleeding was higher for rivaroxaban with aspirin compared to aspirin, but severe bleeding was not increased. The net clinical benefit of rivaroxaban plus aspirin was 20% higher compared with aspirin alone [HR 0.80 (95% CI 16.3%-31.6%)]. Rivaroxaban alone had no benefit on MACE outcomes compared with aspirin alone. MACE outcomes were similar for those on and off randomized treatment. CONCLUSIONS: Low dose rivaroxaban with aspirin significantly reduces first and total cardiovascular events compared with aspirin alone with a NNT2y of 63 and a 20% net clinical benefit.

Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance.

Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na+ /Ca2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared with neurons. To assess the role of NCLX in mouse primary culture astrocytes, we inhibited its function both pharmacologically or genetically. This resulted in re-shaping of cytosolic Ca2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca2+ -dependent manner. Interestingly, in vivo genetic deletion of NCLX in hippocampal astrocytes improved cognitive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX impaired cognitive performance. These results unveil a role for NCLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.

Water vulnerability to pesticide contamination in a Brazilian semiarid watershed.

This study aimed to prepare an inventory of the main active ingredients of pesticides and estimate the risk of pollution of groundwater and surface water resources in a Brazilian semiarid basin. The inventory was prepared using data from government agency databases. The contamination risk estimate was obtained using the GOSS index, Groundwater Ubiquity Score (GUS), Groundwater Screening Index (GSI), Leachability Index (LIX), US Environmental Protection Agency (USEPA) criteria, Leaching Index (LEACH), and Relative Leaching Potential Index (RLPI). The inventory identified 57 active ingredients commercialized under a well-defined chemical class. Most of these (51.5%) belong to the very dangerous class, while 43.6% belong to the moderately toxic class. The GOSS model showed that 23.7% of the active ingredients have a low potential, 50.85% have a moderate potential, and 13.56% have a high potential for surface water contamination, with its transport being associated with the sediment. The GUS index indicates a low potential for groundwater contamination. However, the GSI points to a high potential for water contamination, the USEPA criteria for a possible contamination of groundwater, and, according to the LIX, most of the pollutants do so by leaching. The information provided contributes to the management of xenobiotic compounds in arid and semiarid basins, adding to the water security effort by providing tools for the assessment of potential pesticide pollution. Integr Environ Assess Manag 2023;19:804-816. © 2022 SETAC.