Miracle-dz/UniFAR-FTUs huggingface dataset:
GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans

Significance GABAergic signaling is crucial for the physiological function and the pathological onset of neuropsychiatric disorder, but its roles in innate immunity remain unknown. Here, we reveal that pathogen Pseudomonas aeruginosa infection up-regulates the expression of synaptic components and enhances synaptic strength at GABAergic neuromuscular junctions, induces insulin-like peptide INS-31 in the muscles, and ultimately suppresses innate immunity in the intestine of C. elegans. This signaling axis of synapse–muscular insulin–intestinal innate immunity may play an important role in the maintenance of immunological homeostasis to promote host survival. GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of Caenorhabditis elegans results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAAR-deficient unc-49 mutant compared with wild-type animals. C. elegans with ins-31 knockdown or loss of function exhibited enhanced resistance to Pseudomonas aeruginosa PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse–muscular insulin–intestinal innate immunity in vivo.
Comparison of physiognomy and frame angle parameters using different devices to prescribe progressive addition lenses

ABSTRACT Clinical relevance Accurate measurement of several physiognomy parameters (interpupillary, nasopupillary and fitting height distances) and frame angles (pantoscopic and frame wrap angles) is essential for prescribing progressive addition lenses for presbyopic patients. Background Few reports have described the repeatability of different devices commonly used to conduct essential measurements for prescribing progressive addition lenses. Methods Interpupillary, nasopupillary (at far and near distances) and fitting point heights were measured three consecutive times in 21 healthy volunteers with four devices (traditional frame ruler, PD-5 interpupilometer, OptiCenter, and VisiOffice). Pantoscopic and wrap frame angles were also measured three times with Essilor standard pantoscopic ruler, Opticenter and VisiOffice. Results The frame ruler, PD-5 and Opticenter showed better repeatability for interpupillary and nasopupillary distance (co-efficient of variation close to 1%, within-subject standard deviation or Sw < 0.50 mm) measurements at far and near distances than Visioffice (co-efficient of variation > 2%, Sw > 0.50 mm). Fitting point heights measurements showed worse repeatability with all devices (frame ruler: co-efficient of variation close to 5%, Sw = 0.46 mm; Opticenter co-efficient of variation > 5%, Sw > 0.80 mm; Visioffice co-efficient of variation > 10%, Sw > 1.50 mm). Pantoscopic angle measurements showed very low repeatability with the ruler and Opticenter (co-efficient of variation > 25%, Sw > 1.90 mm). The frame wrap angle showed unacceptable repeatability values with the ruler (co-efficient of variation > 10%, Sw = 0.49º) and Visioffice (co-efficient of variation > 60%, Sw > 2.50º), but acceptable repeatability with Opticenter (co-efficient of variation < 1%, Sw = 0.05º). Conclusions Interpupillary and nasopupillary distance measurement showed acceptable repeatability with all the assessed methods; however, these measurements alone are no longer sufficient for free-form progressive addition lens prescription, which requires fitting point heights and pantoscopic and frame wrap angle measurement. Such measures display a lack of repeatability that could induce centration errors and could affect vision and/or adaptation of the user.
Evaluating Neurotrophin Signaling Using MicroRNA Perilymph Profiling in Cochlear Implant Patients With and Without Residual Hearing

Supplemental Digital Content is available in the text Hypothesis: MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph. Background: Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels. Methods: Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients’ preoperative pure-tone average. Results: Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients. Conclusions: Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.
Mitochondrial ATP Synthase Subunit d, a Component of the Peripheral Stalk, is Essential for Growth and Heat Stress Tolerance in Arabidopsis thaliana

As rapid changes in climate threaten global crop yields, an understanding of plant heat stress tolerance is increasingly relevant. Heat stress tolerance involves the coordinated action of many cellular processes and is particularly energy demanding. We acquired a knockout mutant and generated knockdown lines in Arabidopsis thaliana of the d subunit of mitochondrial ATP synthase (gene name: ATPQ, AT3G52300, referred to hereafter as ATPd), a subunit of the peripheral stalk, and used these to investigate the phenotypic significance of this subunit in normal growth and heat stress tolerance. Homozygous knockout mutants for ATPd could not be obtained due to gametophytic defects, while heterozygotes possess no visible phenotype. Therefore, we used RNAi to create knockdown plant lines for further studies. Proteomic analysis and blue native gels revealed that ATPd downregulation impairs only subunits of the mitochondrial ATP synthase (complex V of the electron transport chain). Knockdown plants were more sensitive to heat stress, had abnormal leaf morphology, and were severely slow growing compared to wild type. These results indicate that ATPd plays a crucial role in proper function of the mitochondrial ATP synthase holoenzyme, which, when reduced, leads to wide-ranging defects in energy-demanding cellular processes. In knockdown plants, more hydrogen peroxide accumulated and mitochondrial dysfunction stimulon (MDS) genes were activated. These data establish the essential structural role of ATPd and provide new information about complex V assembly and quality control, as well as support the importance of mitochondrial respiration in normal plant growth and heat stress tolerance. SIGNIFICANCE STATEMENT The energy converter, mitochondrial ATP synthase, is critical for all organisms, but the functional importance of ATP synthase subunit d remains largely unknown in plants. We demonstrate the contributions of subunit d to plant growth, development, and heat stress tolerance, as well as to ATP synthase stability, ROS signaling and mitochondrial dysfunction regulation.
Management of childhood and adolescent latent tuberculous infection (LTBI) in Germany, Austria and Switzerland

Background Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017. Methods Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS. Results A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%. Conclusion This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.
Reconstructing a Wild-Type Pseudomonas aeruginosa Reference Strain PAO1

The P. aeruginosa reference strain PAO1 carries a regulatory mutation that may affect processes characterized in it. To eliminate complications due to the mutation, we constructed a version of the missing wild-type parent strain and developed methods to transfer mutations between PAO1 and the new strain. The methods are likely to be applicable to other isolates of P. aeruginosa as well. ABSTRACT The P. aeruginosa reference strain PAO1 has been used to delineate much of the physiology, metabolism, and fundamental biology of the species. The wild-type parent of PAO1 was lost, and PAO1 carries a regulatory mutation introduced for positive genetic selection that affects antibiotic resistance, virulence, quorum sensing, and other traits. The mutation is a loss-of-function change in an oxidoreductase gene (mexS), which constitutively activates a stress response controlled by a positive regulator (MexT). Fitness defects associated with the constitutive response have led to the inadvertent selection of mexT-minus suppressor mutations, creating genetic heterogeneity in PAO1 sublines studied in different laboratories. To help circumvent complications due to the mexS-minus phenotypes, we created a wild-type version of PAO1 (called LPAO) by “reverting” its mexS to the functional allele likely to have been in its parent. Phenotypic analysis revealed that the mexS-minus allele in PAO1 makes growth sensitive to salt (NaCl) and is lethal when combined with mutations inactivating the major sodium antiporter (ShaABCDEF). The salt sensitivity of PAO1 may underlie some complex mexS-minus phenotypes and help explain the selection of mexT-minus suppressor mutations. To facilitate genetic comparisons of PAO1, LPAO, and other P. aeruginosa strains, we developed a transformation procedure to transfer selectable alleles, such as transposon insertion alleles, between strains. Overall, the study helps explain phenotypic heterogeneity of PAO1-derived strains and provides resources to help recognize and eliminate difficulties due to it. IMPORTANCE The P. aeruginosa reference strain PAO1 carries a regulatory mutation that may affect processes characterized in it. To eliminate complications due to the mutation, we constructed a version of the missing wild-type parent strain and developed methods to transfer mutations between PAO1 and the new strain. The methods are likely to be applicable to other isolates of P. aeruginosa as well.
ANEMI3: An updated tool for global change analysis

The ANEMI model is an integrated assessment model of global change that emphasizes the role of water resources. The model is based on the principles of system dynamics simulation to analyze changes in the Earth system using feedback processes. Securing water resources for the future is a key issue of global change, and ties into global systems of population growth, climate change, carbon cycle, hydrologic cycle, economy, energy production, land use and pollution generation. Here the third iteration of the model–ANEMI3 is described, along with the methods used for parameter estimation and model testing. The main differences between ANEMI3 and previous versions include: (i) implementation of the energy-economy system based on the principles of system dynamics simulation; (ii) incorporation of water supply as an additional sector in the global economy that parallels the production of energy; (iii) inclusion of climate change effects on land yield and potentially arable land for food production, and (iv) addition of nitrogen and phosphorus based nutrient cycles as indicators of global water quality, which affect the development of surface water supplies. The model is intended for analyzing long-term global feedbacks which drive global change. Because of this, there are limitations related to the spatial scale that is used. However, the model’s simplicity can be considered a strength, as it allows for the driving feedbacks to be more easily identified. The model in its current form allows for a variety of scenarios to be created to address global issues such as climate change from an integrated perspective, or to examine the change in one model sector on Earth system behaviour. The endogenous structure of the model allows for global change to be driven entirely by model structure rather than exogenous inputs. The new additions to the ANEMI3 model are found to capture long term trends associated with global change, while allowing for the development of water supplies to be represented using an integrated approach considering global economy and surface water quality.
The epidemiology of amoebiasis in Thi-Qar Province, Iraq (2015-2020): differentiation of Entamoeba histolytica and Entamoeba dispar using nested and real-time polymerase chain reaction

OBJECTIVES The objective of this study was to evaluate the present status of amoebiasis in Thi-Qar Province in southern Iraq, and to determine the presence of Entamoeba histolytica and Entamoeba dispar with nested and real-time polymerase chain reaction (PCR). METHODS Epidemiological data were obtained from the public health department of the Thi-Qar Health Office (2015-2020). Eighty stool samples were also randomly collected from patients ≤12 year of age with diarrhea at 2 hospitals between the beginning of February 2020 and the end of October 2020. These samples were selected after microscopy to identify the 18S rRNA gene in Entamoeba DNA. RESULTS Of the 341,554 cases of intestinal parasitic infections, 38,004 (11.1%) individuals were recorded as having amoebiasis, which accounted for the highest proportion of infections in 2015 (26.1%) and the lowest in 2020 (8.1%). Amoebiasis was distributed among all age groups, with the age group of 5-14 years accounting for the highest proportion (27.3%). In molecular testing, 42 (52.5%) out of 80 samples were positive for the 18S rRNA gene (888 bp). Using nested PCR, E. histolytica (439 bp) was detected in 25 (31.3%) samples and E. dispar (174 bp) in 14 (17.5%), while using real-time PCR, E. histolytica and E. dispar were detected in 28 (35.0%) and 15 (18.8%) samples, respectively. CONCLUSIONS Epidemiological data confirmed that amoebiasis is endemic in this province, and is not limited to certain months. Our study confirms the applicability of molecular identification to detect pathogenic and non-pathogenic Entamoeba to prescribe the appropriate drug.
Crowdsourced Tick Image-Informed Updates to U.S. County Records of Three Medically Important Tick Species

Abstract Burgeoning cases of tick-borne disease present a significant public health problem in the United States. Passive tick surveillance gained traction as an effective way to collect epidemiologic data, and in particular, photograph-based tick surveillance can complement in-hand tick specimen identification to amass distribution data and related encounter demographics. We compared the Federal Information Processing Standards (FIPS) code of tick photos submitted to a free public identification service (TickSpotters) from 2014 to 2019 to published nationwide county reports for three tick species of medical concern: Ixodes scapularis Say (Ixodida: Ixodidae), Ixodes pacificus Cooley and Kohls (Ixodida: Ixodidae), and Amblyomma americanum Linneaus (Ixodida: Ixodidae). We tallied the number of TickSpotters submissions for each tick species according to “Reported” or “Established” criteria per county, and found that TickSpotters submissions represented more than half of the reported counties of documented occurrence, and potentially identified hundreds of new counties with the occurrence of these species. We detected the largest number of new county reports of I. scapularis presence in Michigan, North Carolina, and Texas. Tick image submissions revealed potentially nine new counties of occurrence for I. pacificus, and we documented the largest increase in new county reports of A. americanum in Kentucky, Illinois, Indiana, and Ohio. These findings demonstrate the utility of crowdsourced photograph-based tick surveillance as a complement to other tick surveillance strategies in documenting tick distributions on a nationwide scale, its potential for identifying new foci, and its ability to highlight at-risk localities that might benefit from tick-bite prevention education.
Portrait of drinking water quality in small Quebec municipal utilities

This study of small Quebec municipal drinking water utilities (i.e., those serving 10,000 or fewer people) focuses on a portrait of microbiological water quality (based on total and fecal coliform data) and distribution system management strategies. It also addresses relationships between some important water quality and operational parameters and management strategies, as well as total or fecal coliform occurrences. Along with descriptive analyses, statistical means tests (Student t-tests) were performed to identify significant differences between utilities with high coliform occurrence and utilities with low coliform occurrence according to chlorine dose, distribution system flushings, pipe age, main breakage, and some environmental factors. Even though many interesting trends have been noted, only a few resulted in statistically significant differences. For surface water utilities using chlorination alone, the mean difference of annual system flushings proved statistically significant. In addition, some agricultural land-use indicators within the municipal territory appeared significantly correlated with coliform occurrences.
Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics and Suicide and All-Cause Mortality in Patients With Newly Diagnosed Schizophrenia

Key Points Question Is use of long-acting injectable antipsychotics (LAIs) in patients with newly diagnosed schizophrenia associated with decreased mortality? Findings This cohort study included 2614 patients with schizophrenia who switched to LAIs, and 2614 propensity-matched patients who continued receiving oral antipsychotics (OAPs) of the same compounds. Patients who switched to LAIs had lower mortality and fewer suicide attempts compared with patients who continued receiving the corresponding OAPs, and patients who switched to LAIs within the first 2 years of OAP initiation exhibited a 47% reduction in the risk of suicide mortality compared with patients who continued receiving OAPs. Meaning These findings suggest that LAI use in patients with newly diagnosed schizophrenia should be encouraged because of its association with lower premature mortality.
Zoonotic potential of Newcastle disease virus: Old and novel perspectives related to public health

Newcastle disease virus (NDV) has a worldwide distribution, causing lethal infection in a wide range of avian species. Affected birds develop respiratory, digestive and neurologic symptoms with profound immunosuppression. Mild systemic Newcastle disease (ND) infection restricted to the respiratory and neurological systems can be observed in humans and other non‐avian hosts. Evidence of ND infection and its genome‐based detection have been reported in Bovidae (cattle and sheep), Mustelidae (mink), Cercetidae (hamster), Muridae (mice), Leporidae (rabbit), Camelidae (camel), Suidae (pig), Cercophithecidae (monkeys) and Hominidae (humans). Owing to frequent ND outbreaks in poultry workers, individuals engaged in the veterinary field, including poultry production or evisceration and vaccine production units have constantly been at a much higher risk than the general population. A lethal form of infection has been described in immunocompromised humans and non‐avian species including mink, pig and cattle demonstrating the capability of NDV to cross species barriers. Therefore, contact with infectious material and/or affected birds can pose a risk of zoonosis and raise public health concerns. The broad and expanding host range of NDV and its maintenance within non‐avian species hampers disease control, particularly in disease‐endemic settings.
Normalisation of glucose metabolism by exendin‐4 in the chronic phase after stroke promotes functional recovery in male diabetic mice

Glucagon‐like peptide‐1 (GLP‐1) receptor activation decreases stroke risk in people with Type 2 diabetes (T2D), while animal studies have shown the efficacy of this strategy to counteract stroke‐induced acute brain damage. However, whether GLP‐1 receptor activation also improves recovery in the chronic phase after stroke is unknown. We investigated whether post‐acute, chronic administration of the GLP‐1 receptor agonist, exendin‐4, improves post‐stroke recovery and examined possible underlying mechanisms in T2D and non‐T2D mice.