Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonality, spatial structure, and pathogenic variation in Fusarium fujikuroi from rain-fed rice in southern Laos

Bakanae disease, caused by the fungal phytopathogen Fusarium fujikuroi, can be detected in most rice (Oryza sativa L.) growing areas worldwide. In this study, we investigated the population structure of this fungus in southern Lao PDR, a country located near the geographic origin of rice domestication. Microsatellites (SSRs) and mating type (MAT) analyses, pathogenicity and fungicide sensitivity tests were integrated in the study. The first key finding is that the population genetic structure of F. fujikuroi in Lao PDR is consistent with high clonal reproduction. Indeed, (i) “true” clones were identified; (ii) within populations, MAT types were frequently skewed from 1:1 ratio, (iii) linkage disequilibrium (among SSRs as also among SSRs and MAT) was present, and (iv) gene-flow between opposite MAT types within the same population is restricted. The presence of genetic divergence among areas and populations and the occurrence of positive spatial autocorrelation of genetic variation, indicate that migration is restricted, and that genetic drift plays an important role in the evolution of this fungus. Two main well-defined groups of isolates were detected (FST = 0.213) that display a non-random spatial distribution. They differ in the ability to induce seedlings death but not seedlings elongation (the typical Bakanae symptom) suggesting that the pathogen’s ability to induce the two symptoms is under different genetic control. Finally, we compared two agroecosystems with contrasting characteristics: low-input and traditional (Lao PDR) vs high-input and modern (Italy). We found differences in the level of population structuring and of spatial autocorrelation. This suggests that the evolutionary potential of the fungus not only depends on its intrinsic characteristics, but is strongly influenced by other external factors, most likely by the dynamics of infested seed exchange. Thus, quarantine and chemical treatments are a way to reduce population connectivity and hence the evolutionary potential of this pathogen.
A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes

Significance Small cell carcinoma of the bladder (SCCB) is a lethal variant of bladder cancer with no effective treatment. A lack of available preclinical models and clinical cohorts impedes our understanding of its molecular pathogenesis. In this study, we provided a tumor model as functional evidence showing that SCCB and other bladder cancer phenotypes can be derived from normal human urothelial cells. We further demonstrated that SCCB has a distinct transcriptome and identified SCCB-associated cell surface proteins (CSPs) that can be further evaluated as potential therapeutic targets. We show that our model shares CSP profile with clinical SCCB samples. Our findings create a foundation to understand the molecular underpinnings of SCCB and provide tools for developing therapeutic strategies. Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB–up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.
Protons in small spaces: Discrete simulations of vesicle acidification

The lumenal pH of an organelle is one of its defining characteristics and central to its biological function. Experiments have elucidated many of the key pH regulatory elements and how they vary from compartment-to-compartment, and continuum mathematical models have played an important role in understanding how these elements (proton pumps, counter-ion fluxes, membrane potential, buffering capacity, etc.) work together to achieve specific pH setpoints. While continuum models have proven successful in describing ion regulation at the cellular length scale, it is unknown if they are valid at the subcellular level where volumes are small, ion numbers may fluctuate wildly, and biochemical heterogeneity is large. Here, we create a discrete, stochastic (DS) model of vesicular acidification to answer this question. We used this simplified model to analyze pH measurements of isolated vesicles containing single proton pumps and compared these results to solutions from a continuum, ordinary differential equations (ODE)-based model. Both models predict similar parameter estimates for the mean proton pumping rate, membrane permeability, etc., but, as expected, the ODE model fails to report on the fluctuations in the system. The stochastic model predicts that pH fluctuations decrease during acidification, but noise analysis of single-vesicle data confirms our finding that the experimental noise is dominated by the fluorescent dye, and it reveals no insight into the true noise in the proton fluctuations. Finally, we again use the reduced DS model explore the acidification of large, lysosome-like vesicles to determine how stochastic elements, such as variations in proton-pump copy number and cycling between on and off states, impact the pH setpoint and fluctuations around this setpoint.
Event-Triggered H∞ Control for T–S Fuzzy Systems via New Asynchronous Premise Reconstruction Approach

This article studies the problem of <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> controller design for discrete-time T–S fuzzy systems under an event-triggered (ET) communication mechanism. By proposing a new asynchronous premise reconstruction approach, new types of ET fuzzy controllers are designed to overcome the challenges caused by the mismatch of premise variables, in which the gains of the designed controllers are automatically updated at different triggering instants according to an online algorithm. By constructing discontinuous Lyapunov functions, it is proved that the proposed ET controllers guarantee the stability and <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> performance of the closed-loop systems. Two examples are provided to verify the validity of the proposed design method.
Essential Ingredients and Innovations in the Design and Analysis of Group-Randomized Trials.

This article reviews the essential ingredients and innovations in the design and analysis of group-randomized trials. The methods literature for these trials has grown steadily since they were introduced to the biomedical research community in the late 1970s, and we summarize those developments. We review, in addition to the group-randomized trial, methods for two closely related designs, the individually randomized group treatment trial and the stepped-wedge group-randomized trial. After describing the essential ingredients for these designs, we review the most important developments in the evolution of their methods using a new bibliometric tool developed at the National Institutes of Health. We then discuss the questions to be considered when selecting from among these designs or selecting the traditional randomized controlled trial. We close with a review of current methods for the analysis of data from these designs, a case study to illustrate each design, and a brief summary. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Barriers and facilitators for caregiver involvement in the home care of people with pressure injuries: A qualitative study

Aim To explore the barriers and facilitators perceived by home caregivers regarding their involvement in the home care of people with pressure injuries. Background Although home caregivers are key in the process of caring for people with pressure injuries, little is known about their perceptions regarding their involvement in the same. Methods A qualitative study based on grounded theory involving a theoretical sample of 15 home caregivers of people with pressure injuries within the health district of Puertollano, Spain. Results This study identified three barriers (feminization of care, necessary life adaptations as a home caregiver, and the organization of health services) and three facilitators (the perceived family duty for caring, willingness to provide care, and satisfaction with the care received on behalf of primary care services) associated with caregiver involvement in the home care of pressure injuries. Conclusions The care of a person with pressure injuries is perceived as a duty and requires important adaptations affecting the home caregiver’s personal, social and work life. The emotional closeness and trust that develops between a patient and the primary care staff equals an involvement which, in turn, also has positive results for both the home caregiver and the patient.
Magnetic Resonance Relaxometry for Determination of Protein Concentration and Aggregation

The water‐proton signal, overwhelmingly considered a nuisance in nuclear magnetic resonance spectroscopy, is advantageously used as a tool to assess protein concentration and to detect protein aggregates in aqueous solutions. The protocols in this article describe use of the water‐proton transverse relaxation rate to determine concentration and aggregate content in protein solutions. Detailed recommendations and description of the parameter settings and data processing ensure successful implementation of this technique, even by a user with limited experience in magnetic resonance relaxometry. All measurements are done noninvasively, in a sealed container, without sampling or otherwise aliquoting the solution. The magnetic resonance relaxometry approach offered in this article could be advantageous for analysis of biologics formulations or when use of conventional analytical techniques is not possible. © 2019 by John Wiley & Sons, Inc.
Rapid domestication of autotrophic nitrifying granular sludge and its stability during long-term operation

ABSTRACT The nitrifying granular sludge process is a prospective technology for the efficient treatment of rare earth mine wastewater in southern Jiangxi, China. However, the long formation time of nitrifying granular sludge greatly restricted its application. In the present study, nitrifying granules were domesticated in a pilot-scale sequencing batch reactor by using heterotrophic granular sludge as carriers and adding exogenous nitrifying bacteria concentrate. According to variations of granular properties and ammonia removal, autotrophic nitrifying granules were successfully domesticated within 38 days using the strategy. It was found that the process involved secondary nucleation and microbial community evolution of the seed heterotrophic granules, and Nitrosomonas replaced most heterotrophic bacteria and became the dominant species with the largest relative abundance. During the subsequent 168 days of operation, the domesticated autotrophic nitrifying granules were stable, and their structures were denser than those of the inoculated granules. The ammonia nitrogen removal rate of the reactor was greater than 90% for a long period of time, and persistent partial nitrification was once achieved. However, severe fluctuation of influent ammonia nitrogen during the 120th to 206th day significantly inhibited the activity of nitrifying bacteria, which gradually led to the decrease of the ammonia nitrogen removal rate. GRAPHICAL ABSTRACT
Disentangling the effects of environment and ontogeny on tree functional dimensions for congeneric species in tropical forests.

1.Soil water and nutrient availability are key drivers of tree species distribution and forest ecosystem functioning, with strong species differences in water and nutrient use. Despite growing evidence for intraspecific trait differences, it remains unclear under which circumstances the effects of environmental gradients trump those of ontogeny and taxonomy on important functional dimensions related to resource use, particularly in tropical forests. 2. Here we explore how physiological, chemical and morphological traits related to resource use vary between life stages in four species within the genus Micropholis that is widespread in lowland Amazonia. Specifically, we evaluate how environment, developmental stage and taxonomy contribute to single trait variation and multi-dimensional functional strategies. 3. We find that environment, developmental stage and taxonomy differentially contribute to functional dimensions. Habitats and seasons shape physiological and chemical traits related to water and nutrient use, while developmental stage and taxonomic identity impact morphological traits -especially those related to the leaf economics spectrum. 4. Our findings suggest that combining environment, ontogeny and taxonomy allows for a better understanding of important functional dimensions in tropical trees and highlight the need for integrating tree physiological and chemical traits with classically-used morphological traits to improve predictions of tropical forests response to environmental change.
SdrA, an NADP(H)‐regenerating enzyme, is crucial for Coxiella burnetii to resist oxidative stress and replicate intracellularly

Coxiella burnetii, the causative agent of the zoonotic disease Q fever, is a Gram‐negative bacterium that replicates inside macrophages within a highly oxidative vacuole. Screening of a transposon mutant library suggested that sdrA, which encodes a putative short‐chain dehydrogenase, is required for intracellular replication. Short‐chain dehydrogenases are NADP(H)‐dependent oxidoreductases, and SdrA contains a predicted NADP+ binding site, suggesting it may facilitate NADP(H) regeneration by C. burnetii, a key process for surviving oxidative stress. Purified recombinant 6×His‐SdrA was able to convert NADP+ to NADP(H) in vitro. Mutation to alanine of a conserved glycine residue at position 12 within the predicted NADP binding site abolished significant enzymatic activity. Complementation of the sdrA mutant (sdrA::Tn) with plasmid‐expressed SdrA restored intracellular replication to wild‐type levels, but expressing enzymatically inactive G12A_SdrA did not. The sdrA::Tn mutant was more susceptible in vitro to oxidative stress, and treating infected host cells with L‐ascorbate, an anti‐oxidant, partially rescued the intracellular growth defect of sdrA::Tn. Finally, stable isotope labelling studies demonstrated a shift in flux through metabolic pathways in sdrA::Tn consistent with the presence of increased oxidative stress, and host cells infected with sdrA::Tn had elevated levels of reactive oxygen species compared with C. burnetii NMII.
EEG- and EOG-Based Asynchronous Hybrid BCI: A System Integrating a Speller, a Web Browser, an E-Mail Client, and a File Explorer

This paper presents a new asynchronous hybrid brain-computer interface (BCI) system that integrates a speller, a web browser, an e-mail client, and a file explorer using electroencephalographic (EEG) and electrooculography (EOG) signals. More specifically, an EOG-based button selection method, which requires the user to blink his/her eyes synchronously with the target button’s flashes during button selection, is first presented. Next, we propose a mouse control method by combining EEG and EOG signals, in which the left-/right-hand motor imagery (MI)-related EEG is used to control the horizontal movement of the mouse and the blink-related EOG is used to control the vertical movement of the mouse and to select/reject a target. These two methods are further combined to develop the integrated hybrid BCI system. With the hybrid BCI, users can input text, access the internet, communicate with others via e-mail, and manage files in their computer using only EEG and EOG without any body movements. Ten healthy subjects participated in a comprehensive online experiment, and superior performance was achieved compared with our previously developed P300- and MI-based BCI and some other asynchronous BCIs, therefore demonstrating the system’s effectiveness.
The mind–body problem: Circuits that link the cerebral cortex to the adrenal medulla

Which regions of the cerebral cortex are the origin of descending commands that influence internal organs? We used transneuronal transport of rabies virus in monkeys and rats to identify regions of cerebral cortex that have multisynaptic connections with a major sympathetic effector, the adrenal medulla. In rats, we also examined multisynaptic connections with the kidney. In monkeys, the cortical influence over the adrenal medulla originates from 3 distinct networks that are involved in movement, cognition, and affect. Each of these networks has a human equivalent. The largest influence originates from a motor network that includes all 7 motor areas in the frontal lobe. These motor areas are involved in all aspects of skeletomotor control, from response selection to motor preparation and movement execution. The motor areas provide a link between body movement and the modulation of stress. The cognitive and affective networks are located in regions of cingulate cortex. They provide a link between how we think and feel and the function of the adrenal medulla. Together, the 3 networks can mediate the effects of stress and depression on organ function and provide a concrete neural substrate for some psychosomatic illnesses. In rats, cortical influences over the adrenal medulla and the kidney originate mainly from 2 motor areas and adjacent somatosensory cortex. The cognitive and affective networks, present in monkeys, are largely absent in rats. Thus, nonhuman primate research is essential to understand the neural substrate that links cognition and affect to the function of internal organs.
Is oral anticoagulation effective in preventing transcatheter aortic valve implantation failure? A propensity matched analysis of the Italian Transcatheter balloon-Expandable valve Registry study.

BACKGROUND Early hypo-attenuated leaflet thickening after transcatheter aortic valve implantation (TAVI) has been recently described presumably reflecting thrombus apposition. Although its clinical relevance is still unknown, oral anticoagulant therapy (OAT) led to almost complete resolution. METHODS The retrospecitve Italian Transcatheter balloon-Expandable valve registry that included all patients undergoing balloon-expandable TAVI in 33 Italian centers. Patients discharged after TAVI with aspirin alone were compared with those assuming aspirin and OAT before and after propensity score with matching. Prosthetic heart valve dysfunction at follow-up was the primary end point. All-cause death, cardiovascular death, bleeding, vascular complications and cerebrovascular accidents at 30 days and at follow-up were the secondary ones. RESULTS Among the 1904 patients enrolled in the Italian Transcatheter balloon-Expandable valve registry, 716 patients on OAT and aspirin or aspirin alone were identified and analyzed: 555 were on aspirin alone and 161 on OAT and aspirin. The median follow-up was 44.0 ± 12 months. After matching, risk of prosthetic valve dysfunction at follow-up did not differ between the two groups: 3.1% in patients treated with aspirin alone vs. 1.9% in those treated with OAT and aspirin, (P = 0.72). Nevertheless patients treated with aspirin alone at follow-up had a significantly lower risk of death (21 vs. 33%, P = 0.03) and major bleeding (4 vs. 14%, P = 0.04) with a similar rate of stroke/transient ischemic attack (TIA) (1.2 vs. 3.1%, P = 0.45). At 30 days rates of Valve Academic Research Consortium death were similar in both groups (0.6 vs. 3.7%, P = 0.12) with higher risk of life threatening bleeding and minor vascular complications in patients on OAT and aspirin. CONCLUSION After TAVI with Edwards Sapien valve OAT did not reduce the incidence of valve dysfunction and stroke but was responsible for mortality and bleeding increases.
Dipole-wind interactions under gap wind jet conditions in the Gulf of Tehuantepec, Mexico: A surface drifter and satellite database analysis

Gap wind jets (Tehuano winds) trigger supersquirts of colder water and mesoscale asymmetric dipoles in the Gulf of Tehuantepec (GT). However, the effects of successive gap wind jets on dipoles and their effects inside eddies have not yet been studied. Based on the wind fields, geostrophic currents, and surface drifter dispersion, this research documented three dipoles triggered and modified by Tehuano winds. Once a dipole develops, successive gap wind jets strengthen the vortices, and the anticyclonic eddy migrates southwestward while the cyclonic eddy is maintained on the east side of the GT. During the wind relaxation stage, the cyclonic eddy may propagate westward, but due to the subsequent re-intensification of the Tehuano winds, the vortex could break down, as was suggested by surface drifter dispersion pattern and geostrophic field data. The effect of the Tehuano winds was evaluating via eddy-Ekman pumping. Under Tehuano wind conditions, Ekman downwelling (upwelling) inside the anticyclonic (cyclonic) eddies may reach ~ -2.0 (0.5) m d-1 and decrease as the wind weakens. In the absence of Tehuano winds, Ekman downwelling inside the anticyclonic eddy was ~ 0.1 (-0.1) m d-1. The asymmetry of downwelling and upwelling inside eddies during Tehuano wind events may be associated with Tehuano wind forcing.