Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelets Endocytose Viral Particles and Are Activated via TLR (Toll-Like Receptor) Signaling

Supplemental Digital Content is available in the text. Objective: Thrombocytopenia is associated with many viral infections suggesting virions interact with and affect platelets. Consistently, viral particles are seen inside platelets, and platelet activation markers are detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, and are activated by a model virion. Approach and Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy, and transgenic mouse models, we probed the interactions between platelets and virions. Mouse platelets used known endocytic machinery, that is, dynamin, VAMP (vesicle-associated membrane protein)-3, and Arf6 (ADP-ribosylation factor 6), to take up and traffic HIV-1 pseudovirions. Endocytosed HIV-1 pseudovirions trafficked through early (Rab4+) and late endosomes (Rab7+), and then to an LC3+ (microtubule-associated protein 1A/1B-light chain 3) compartment. Incubation with virions induced IRAK4 (interleukin 1 receptor–associated kinase 4), Akt (protein kinase B), and IKK (IκB kinase) activation, granule secretion, and platelet-leukocyte aggregate formation. This activation required TLRs (Toll-like receptors) and MyD88 (myeloid differentiation primary response protein 88) but was less extensive and slower than activation with thrombin. In vivo, HIV-1 pseudovirions injection led to virion uptake and platelet activation, as measured by IKK activation, platelet-leukocyte aggregate formation, and mild thrombocytopenia. All were decreased in VAMP-3−/− and, megakaryocyte/platelet-specific, Arf6−/− mice. Similar platelet activation profiles (increased platelet-leukocyte aggregates, plasma platelet factor 4, and phospho-IκBα) were detected in newly diagnosed and antiretroviral therapy–controlled HIV-1+ patients. Conclusions: Collectively, our data provide mechanistic insights into the cell biology of how platelets endocytose and process virions. We propose a mechanism by which platelets sample the circulation and respond to potential pathogens that they take up.
MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection

Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNFα when compared to SIV-naïve MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease.
Seletividade de herbicidas pós-emergentes na cultura da mandioca

The cassava response to herbicide application varies from complete selectivity to full production loss due to the poisoning caused. Thus, the objective of this work was to evaluate the selectivity of herbicides applied at post-emergence in cassava. An experiment was arranged in a randomized block design, under greenhouse conditions, including 23 treatments (22 herbicides + control) and four replications. The herbicides were applied 60 days after cassava shooting, when the plants displayed 15 completely-expanded leaves. Intoxication of cassava plants was evaluated weekly and 35 days after the plants were harvested for dry matter determination. The best visible symptoms of cassava intoxication occurred 21 days after planting for most tested products. At the end of the evaluation period, the cassava plants presented visual signals of recovery from the damage caused by the herbicides. Ametryn, ametryn + trifloxysulfuron-sodium, atrazine, diuron + hexazinone andsulfentrazone caused the greatest reductions of dry matter and the worst visible damage. Contrarily, bentazon,fluazifop-p-butil, mesotrione, and tembotrione were the least toxic to the culture. Cassava presents different levels of selectivity to the herbicides, and bentazon,fluazifop-p-butyl, mesotrione, and tembotrione present a potential active principle for use in weed control management programs.
High rates of daytime respiration in three streams: Use of δ18OO2 and O2 to model diel ecosystem metabolism

Photosynthesis and respiration determine the carbon and oxygen (O2) balance of ecosystems. Current methods used to estimate ecosystem respiration (ER) do not include diel ER fluctuations, which limit testing predictions about short‐term drivers of ecosystem metabolism. Diel changes in δ18OO22 can be used to estimate diel ER due to discrimination against δ18OO22 during respiration. We monitored diel δ18OO22, O2, light, and water temperature in three Wyoming streams and measured respiration fractionation (αR) against δ18OO22 in dark benthic flow chambers in two streams. The ranges of measured and literature αR values were used to estimate uncertainty in metabolism parameters associated with not measuring αR directly. Daytime ER was 54–340% higher than nighttime ER using δ18OO22, but diel ER parameter estimates were highly uncertain relative to traditional estimates of ecosystem metabolism. Diel variations in water temperature only accounted for 4–55% of the range of diel ER calculated using diel δ18OO22. Measured benthic flow chamber αR varied within the range of literature values: from 0.9755 to 0.9954. Metabolism parameter estimates were very sensitive to choice of αR within the measured and published range of values. The mean and uncertainty of diel ER estimates increased with decreasing αR, with daily ER more than ten times higher given an αR of 0.975 vs. 0.999. Diel changes in ER can be modeled using δ18OO22 and O2, but diel ER estimates depend on the choice of αR, suggesting the need to better understand how αR may vary within spatial and temporal scales appropriate for δ18OO22 metabolism models.
Genotype–phenotype correlation in children with hereditary spherocytosis

Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease‐causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 and SPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1‐HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1‐HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling.
Crystal and molecular structure of the amylose–DMSO complex

The crystal and molecular structure of the complex of amylose with dimethyl sulfoxide has been studied by a combination of stereochemical analysis, potential energy, and X‐ray diffraction methods. The complex crystallizes in a pseudotetragonal unit cell with a = b = 19.17 Å and c (fiber axis) = 24.39 Å, with two antiparallel chains per unit cell and space group P212121. The amylose chain is a left‐handed 61(1.355) helix with three turns per crystallographic repeat. The O(6) rotational position is approximately gt. Dimethyl sulfoxide is located inside the helix with one DMSO molecule for every three glucose residues. An additional four DMSO molecules and eight water molecules each are located in the large interstices between chains, and it is the interaction of these molecules with the helix that results in the pseudotetragonal chain packing. The interstitial DMSO is the source of the previously reported additional layer lines, which are not consistent with the 8.13‐Å amylose repeat distance. The final R factor for the layers with amylose contribution to the structure factors was 0.29, while the overall R factor was 0.35. The stereochemical packing analysis provided suitable phasing models for the subsequent X‐ray refinement.
Annual clovers (Trifolium spp.) have different reproductive strategies to achieve persistence in Mediterranean-type climates

The aim of this work was to determine whether different species of annual clover (Trifolium spp.), obtained from the same environment, have different reproductive strategies (combinations of reproductive traits) to achieve ecological success. A better understanding of the traits that improve persistence should allow agronomists to narrow the selection criteria for new clover cultivars for ley-farming systems in southern Australia. Seeds of 18 annual clover species were obtained from 3 Australian and 6 Mediterranean sites and were subsequently grown in a common garden in Western Australia. Reproductive traits, including time of flowering, weight per seed, fecundity, pollen to ovule ratio, and pattern of seed softening, were observed. Accessions of different clover species from the same site of collection had different reproductive strategies. Across a range of collection sites, accessions of the same species demonstrated the same broad reproductive strategy; however, some traits, e.g. the timing of flowering, varied within species across collection sites. Principal component analysis suggested that there are 3 broad reproductive strategies demonstrated by these clover species. At one extreme were the relatively large-seeded clovers (T. subterraneum, T. clypeatum, and T. stellatum). The associated cost of these large seeds is reduced fecundity. The large-seeded clovers do not have high long-term hardseededness (the predominant form of seed dormancy in clovers). The relatively small-seeded clovers were all characterised by high fecundity. Many of the small-seeded clovers have high levels of long-term hardseededness, which allow the risk of failure to be spread across seasons (T. spumosum, T. hirtum, T. lappaceum, T. angustifolium, and T. tomentosum). Some of the small-seeded clovers (T. glomeratum, T. nigrescens, T. campestre, T. cernuum, and T. suffocatum) are generalists, producing as many seeds as possible in each season, with very little hardseededness. There are several possible explanations for the apparent success of such different reproductive strategies among clover accessions of different species at the same site. A plant may achieve the same goal by trading one reproductive trait for another. For example, it may either produce many small seeds to spread the risk of failure or produce fewer large seeds with an inherent competitive advantage. Alternatively, temporal and spatial variation may favour clovers with a number of different reproductive strategies. It is likely that a mixture of species with different reproductive strategies will maximise production and persistence of legume-based pastures in ley-farming systems.
Fixed‐ratio combination of basal insulin and glucagon‐like peptide‐1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge

Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation because of the progressive nature of T2D, this appears to be suboptimal in Japanese real‐world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean glycated haemoglobin >9%). Although basal insulin therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose often remains uncontrolled. Basal‐bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed‐ratio combinations (FRCs) of BI and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have shown efficacy in reducing both FPG and postprandial plasma glucose with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide, is currently available in Japan and the United States/European Union at a ratio of 1 U (unit):0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 1:1 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D.
Diagnostic accuracy and reproducibility of optical flow ratio for functional evaluation of coronary stenosis in a prospective series.

BACKGROUND Evaluating prospectively the feasibility, accuracy and reproducibility of optical flow ratio (OFR), a novel method of computational physiology based on optical coherence tomography (OCT). METHODS AND RESULTS Sixty consecutive patients (76 vessels) underwent prospectively OCT, angiography-based quantitative flow ratio (QFR) and fractional flow ratio (FFR). OFR was computed offline in a central core-lab by analysts blinded to FFR. OFR was feasible in 98.7% of the lesions and showed excellent agreement with FFR (ICCa = 0.83, r = 0.83, slope = 0.80, intercept = 0.17, kappa = 0.84). The area under curve to predict an FFR ≤ 0.80 was 0.95, higher than for QFR (0.91, p = 0.115) and for minimal lumen area (0.64, p < 0.001). Diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 93%, 92%, 93%, 88%, 96%, 13.8, 0.1, respectively. Median time to obtain OFR was 1.07 (IQR: 0.98-1.16) min, with excellent intraobserver and interobserver reproducibility (0.97 and 0.95, respectively). Pullback speed had negligible impact on OFR, provided the same coronary segment were imaged (ICCa = 0.90, kappa = 0.697). CONCLUSIONS The prospective computation of OFR is feasible and reproducible in a real-world series, resulting in excellent agreement with FFR, superior to other image-based methods.
American Indian Reservations and COVID-19: Correlates of Early Infection Rates in the Pandemic

Objective: To determine the household and community characteristics most closely associated with variation in COVID-19 incidence on American Indian reservations in the lower 48 states. Design: Multivariate analysis with population weights. Setting: Two hundred eighty-seven American Indian Reservations and tribal homelands (in Oklahoma) and, as of April 10, 2020, 861 COVID-19 cases on these reservation lands. Main Outcome Measures: The relationship between rate per 1000 individuals of publicly reported COVID-19 cases at the tribal reservation and/or community level and average household characteristics from the 2018 5-Year American Community Survey records. Results: By April 10, 2020, in regression analysis, COVID-19 cases were more likely by the proportion of homes lacking indoor plumbing (10.83, P = .001) and were less likely according to the percentage of reservation households that were English-only (−2.43, P = .03). Household overcrowding measures were not statistically significant in this analysis (−6.40, P = .326). Conclusions: Failure to account for the lack of complete indoor plumbing and access to potable water in a pandemic may be an important determinant of the increased incidence of COVID-19 cases. Access to relevant information that is communicated in the language spoken by many reservation residents may play a key role in the spread of COVID-19 in some tribal communities. Household overcrowding does not appear to be associated with COVID-19 infections in our data at the current time. Previous studies have identified household plumbing and overcrowding, and language, as potential pandemic and disease infection risk factors. These risk factors persist. Funding investments in tribal public health and household infrastructure, as delineated in treaties and other agreements, are necessary to protect American Indian communities.
UNCERTAINTY AND VARIABILITY IN DEMOGRAPHY AND POPULATION GROWTH: A HIERARCHICAL APPROACH

Estimates of uncertainty are the basis for inference of population risk. Uncertainty is estimated from models fitted to data that typically include a deterministic model (e.g., population growth) and stochastic elements, which should accommodate errors in sampling and any sources of variability that affect observations. Prediction from fitted models (of, say, demography) to new variables (say, population growth) requires propagation of these stochastic elements. Ecological models ignore most forms of variability, because they make statistical models complex, and they pose computational challenges. Variability associated with space, time, and among individuals that is not accommodated by demographic models can make parameter estimates and growth rate predictions unrealistic. I adapt a hierarchical approach to the problem of estimating population growth rates and their uncertainties when individuals vary and that variability cannot be assigned to specific causes. In contrast to an overfitted model that would assign a different parameter value to each individual, hierarchical models accommodate individual differences, but assume that those differences derive from an underlying distribution—they belong to a “population. ” The hierarchical model can be implemented in classical (frequentist) and Bayesian frameworks (I demonstrate both) and analyzed using Markov chain Monte Carlo simulation. Results show that population growth models that rely on standard propagation of estimation error but ignore variability among individuals can misrepresent uncertainties in ways that erode credibility. Corresponding Editor: O. N. Bjornstad.
Comparative evaluation of 4 commercial modified‐live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines against heterologous dual Korean PRRSV‐1 and PRRSV‐2 challenge

Abstract Background Four commercial porcine reproductive and respiratory syndrome virus (PRRSV) modified‐live vaccines (MLV) was compared to protect growing pigs against dual challenge of PRRSV‐1 and PRRSV‐2. Methods Two of the vaccines were based on PRRSV‐1, and two on PRRSV‐2. A total of 72 PRRSV‐naïve pigs were divided into six groups (12 pigs/group). Results Two PRRSV‐1 MLV‐vaccinated and two PRRSV‐2 MLV‐vaccinated groups reduced significantly (p < .05) genomic copies of PRRSV‐1 in their sera compared to the unvaccinated challenged group. Two PRRSV‐2 MLV‐vaccinated groups reduced significantly (p < .05) fewer genomic copies of PRRSV‐2 in their sera whereas two PRRSV‐1 MLV‐vaccinated groups were unable to reduce genomic copies of PRRSV‐2 compared to unvaccinated challenged groups. Two PRRSV‐1 MLV‐vaccinated groups induced a stronger PRRSV‐1 specific IFN‐γ‐SC response, while two PRRSV‐2 MLV‐vaccinated groups induced a stronger PRRSV‐2 specific IFN‐γ‐SC response. Two PRRSV‐2 MLV‐vaccinated groups showed significantly (p < .05) lower mean macroscopic and microscopic lung lesion scores compared to two PRRSV‐1 MLV‐vaccinated groups. Conclusions These data demonstrated that two PRRSV‐2 vaccines were efficacious and exhibited similar protection while, two PRRSV‐1 vaccines were largely ineffective against the dual challenge.
Comparison of soft tissue chin thickness at different levels of chin in subjects with various growth patterns

Aims and Objectives: To evaluate the association between mandibular growth pattern and soft tissue chin (STC) thickness measured at different chin levels and the gender differences in STC thickness at these different chin levels. Materials and Methods: Pretreatment lateral cephalograms of 161 subjects aged 18–45 years were selected, and subjects were divided into 4 groups depending on mandibular growth pattern defined by the mandibular plane to cranial base angle. The STC thicknesses were measured at pogonion (Pog), gnathion (Gn), and menton (Me). Group difference was evaluated using analysis of variance. Results: STC thickness was greater (p < .05) in the low-angle group, and it gradually decreased across the groups, the least being in the high-angle group. No sexual dimorphism was observed among the groups (p > .05). Conclusion: This study suggests that STC thickness measurements were smaller in high-angle group compared to low-angle group.
The suitability of muscle of Cirrhinus mrigala in the formation of gel: a comparative electrophoretic study of six tropical carp meats

Summary The annual inland fish production in India is 3.2 million tonnes and above. Aquaculture is around 80% of total inland fish production. The enhanced aquaculture production demands alternate processing methods for better utilisation of the farmed fish. Cirrhinus mrigala is one of the dominated species among cultured Indian major carps, but rated with lowest price. Fish meat with good gel-forming capacity is a prerequisite in the production of fast-moving fabricated analogue product. Cirrhinus mrigala had the highest gel strength, i.e. 435 gcm of its fresh meat in comparison with other carps. Apart from the highest protein and salt-soluble protein nitrogen content in fresh C. mrigala meat, this article also reports that the presence of the darkest thick band of myosin heavy chain and actin in the polyacrylamide gel electrophoresis pattern of salt-soluble extract of C. mrigala might be another possible reason for the highest gel strength in comparison with other carps. Cirrhinus mrigala contained white meat around 90%. This carp could be suitably used in the preparation of high-valued fabricated analogue product.