Miracle-dz/UniFAR-FTUs huggingface dataset:
TRIM22 inhibits respiratory syncytial virus replication by targeting JAK‐STAT1/2 signaling

Respiratory syncytial virus (RSV) infection is a major cause of lower respiratory tract disease. Although RSV causes major economic losses every year, effective treatments have not been found so far. Recent studies have shown that the tripartite motif‐containing (TRIM) superfamily plays an essential role in the immune response. In this study, we found that TRIM22 had an inhibitory effect on RSV infection, and downregulation of TRIM22 moderately enhanced RSV replication. Our data further demonstrated that RSV infection induced TRIM22 expression through the activation of JAK‐STAT1/2 signaling. RSV infection also induced TRIM22 expression. Taken together, these data points showed that the TRIM family member, TRIM22, had an essential role in resisting RSV infection, and this effect was closely related to the JAK‐STAT1/2 pathway. Our results provide promising evidence for a novel target for the prevention and treatment of RSV.
Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double-blind, randomised controlled trial among non-pregnant Cambodian women

Introduction The WHO recommends daily oral iron supplementation for 12 weeks in women and adolescents where anaemia prevalence is greater than 40%. However, if iron deficiency is not a major cause of anaemia, then, at best, untargeted iron supplementation is a waste of resources; at worst, it could cause harm. Further, different forms of iron with varying bioavailability may present greater risks of harm. Methods and analysis A 12-week three-arm, double-blind, randomised controlled supplementation trial was conducted in Cambodia to determine if there is potential harm associated with untargeted iron supplementation. We will recruit and randomise 480 non-pregnant women (ages 18–45 years) to receive one of three interventions: 60 mg elemental iron as ferrous sulfate (the standard, commonly used form), 18 mg ferrous bisglycinate (a highly bioavailable iron amino acid chelate) or placebo. We will measure ferritin concentrations (to evaluate non-inferiority between the two forms of iron), as well as markers of potential harm in blood and stool (faecal calprotectin, gut pathogen abundance and DNA damage) at baseline and 12 weeks. Mixed-effects generalised linear models will be used to assess the effect of iron on ferritin concentration and markers of potential harm at 12 weeks. Ethics and dissemination Ethical approval was obtained from the University of British Columbia Clinical Research Ethics Board (H18-02610), the Children's and Women's Health Centre of British Columbia Research Ethics Board (H18-02610) and the National Ethics Committee for Health Research in Cambodia (273-NECHR). Findings will be published in peer-reviewed journals, presented to stakeholders and policymakers globally and shared within participants’ communities. Trial registration number ClinicalTrials.gov Registry (NCT04017598).
Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

Trypanosoma cruzi is a remarkably versatile parasite. It can parasitize almost any nucleated cell type and naturally infects hundreds of mammal species across much of the Americas. In humans, it is the cause of Chagas disease, a set of mainly chronic conditions predominantly affecting the heart and gastrointestinal tract, which can progress to become life threatening. Yet around two thirds of infected people are long‐term asymptomatic carriers. Clinical outcomes depend on many factors, but the central determinant is the nature of the host‐parasite interactions that play out over the years of chronic infection in diverse tissue environments. In this review, we aim to integrate recent developments in the understanding of the spatial and temporal dynamics of T. cruzi infections with established and emerging concepts in host immune responses in the corresponding phases and tissues.
Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update

Background Schizophrenia is a serious mental illness that affects more than 21 million people worldwide. Both genetics and the environment play a role in its etiology and pathogenesis. Symptoms of schizophrenia are mainly categorized into positive, negative, and cognitive. One major approach to identify and understand these diverse symptoms in humans has been to study behavioral phenotypes in a range of animal models of schizophrenia. Objective We aimed to provide a comprehensive review of the behavioral tasks commonly used for measuring schizophrenia-like behaviors in rodents together with an update of the recent study findings. Methods Articles describing phenotypes of schizophrenia-like behaviors in various animal models were collected through a literature search in Google Scholar, PubMed, Web of Science, and Scopus, with a focus on advances over the last 10 years. Results Numerous studies have used a range of animal models and behavioral paradigms of schizophrenia to develop antipsychotic drugs for improved therapeutics. In establishing animal models of schizophrenia, the candidate models were evaluated for schizophrenia-like behaviors using several behavioral tasks for positive, negative, and cognitive symptoms designed to verify human symptoms of schizophrenia. Such validated animal models were provided as rapid preclinical avenues for drug testing and mechanistic studies. Conclusion Based on the most recent advances in the field, it is apparent that a myriad of behavior tests are needed to confirm and evaluate the congruency of animal models with the numerous behaviors and clinical signs exhibited by patients with schizophrenia.
Protein Kinase D 1 Predicts Poor Treatment Response and Unfavorable Survival of Bortezomib-Based Treatment, and Its Knockdown Enhances Drug Sensitivity to Bortezomib in Multiple Myeloma

Objective: The present study aimed to explore the correlation of protein kinase D 1 with prognosis in bortezomib-treated multiple myeloma patients and further investigate the effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib in multiple myeloma cells. Methods: Totally, 104 de novo symptomatic multiple myeloma patients treated with bortezomib-based regimens and 30 healthy controls were recruited. Bone marrow mononuclear cells–derived plasma cells were collected from multiple myeloma patients before initial treatment and from healthy controls on the bone marrow donation, respectively, then protein kinase D 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction, respectively. The effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib was detected by transfecting protein kinase D 1 knockdown plasmid and control plasmid into RPMI8226 and U266 cells. Results: Protein kinase D 1 protein/messenger RNA expressions were both upregulated in multiple myeloma patients compared with healthy controls and presented good value in differentiating multiple myeloma patients from healthy controls. Furthermore, protein kinase D 1 protein/messenger RNA expressions were both associated with high International Staging System stage and t (4; 14). Furthermore, both complete response rate and overall response rate were reduced in protein kinase D 1 high patients compared with protein kinase D 1 low patients; similarly, progression-free survival and overall survival were both decreased in protein kinase D 1 high patients compared with protein kinase D 1 low patients. In addition, in RPMI8226 and U266 multiple myeloma cells, protein kinase D 1 knockdown increased drug sensitivity to bortezomib. Conclusion: Protein kinase D 1 has the potential to predict poor treatment response and unfavorable survival of bortezomib-based treatment in multiple myeloma patients, and its knockdown enhanced drug sensitivity to bortezomib in multiple myeloma cells.
Olfactory cells responding to the main pheromone component and plant volatiles in Lobesia botrana (Den. & Schiff.): possible effects on monitoring systems.

During the last years electrophysiological and behavioural studies have been carried out in order to establish the role of plant volatile compounds in the host-finding process and oviposition site selection by L. botrana. In previous papers, it has been shown that several compounds are able to stimulate the antennae of both sexes (virgin and mated) of the moth. Results of wind-tunnel studies showed that olfactory cues are greatly involved in the location of host plant and oviposition site. Since olfactory cells sensitive to pheromone components and plant volatiles have been recently found in various insect species, in the present study we applied a single cell recording (SCR) technique (surface contact) to find out olfactory neurons stimulated by the two categories of compounds. The differential saturation electroantennographic technique (DS-EAG) was employed to evaluate the possible decrease of the antennal sensitivity to a plant volatile when the antenna is continuously exposed to E7Z9-12:Ac and, alternatively, to E7Z9-12:Ac when a plant compound is supplied. A large variety of cellular types emerged, from the specific (relatively to the tested compounds) to the highly generalist ones. DS-EAG results showed that cells responding to E7Z9-12:Ac and at least to one plant volatile are widely represented in L. botrana and diverse substances induce a different reduction of the antennal sensitivity to E7Z9-12:Ac. The finding of these cells supports the observations reported by various authors about the ability of plant compounds to enhance or reduce the biological activity of a pheromone component. These “peripheral interferences” in odour perception need to be evaluated when setting up new blends for monitoring purposes.
Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.
Dissecting the genetic overlap of smoking behaviors, lung cancer, and chronic obstructive pulmonary disease: A focus on nicotinic receptors and nicotine metabolizing enzyme

Smoking is a major contributor to lung cancer and chronic obstructive pulmonary disease (COPD). Two of the strongest genetic associations of smoking‐related phenotypes are the chromosomal regions 15q25.1, encompassing the nicotinic acetylcholine receptor subunit genes CHRNA5‐CHRNA3‐CHRNB4, and 19q13.2, encompassing the nicotine metabolizing gene CYP2A6. In this study, we examined genetic relations between cigarettes smoked per day, smoking cessation, lung cancer, and COPD. Data consisted of genome‐wide association study summary results. Genetic correlations were estimated using linkage disequilibrium score regression software. For each pair of outcomes, z‐score‐z‐score (ZZ) plots were generated. Overall, heavier smoking and decreased smoking cessation showed positive genetic associations with increased lung cancer and COPD risk. The chromosomal region 19q13.2, however, showed a different correlational pattern. For example, the effect allele‐C of the sentinel SNP (rs56113850) within CYP2A6 was associated with an increased risk of heavier smoking (z‐score = 19.2; p = 1.10 × 10−81), lung cancer (z‐score = 8.91; p = 5.02 × 10−19), and COPD (z‐score = 4.04; p = 5.40 × 10−5). Surprisingly, this allele‐C (rs56113850) was associated with increased smoking cessation (z‐score = −8.17; p = 2.52 × 10−26). This inverse relationship highlights the need for additional investigation to determine how CYP2A6 variation could increase smoking cessation while also increasing the risk of lung cancer and COPD likely through increased cigarettes smoked per day.
Burden of respiratory syncytial virus hospitalisation among infants born at 32–35 weeks' gestational age in the Northern Hemisphere: pooled analysis of seven studies

Abstract To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000–2014). Data from all 320–356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December–January. Median age at RSVH was 88 days (interquartile range (IQR): 54–159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2–6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2–5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3–7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2–8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3–8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4–6 days for 32–34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32–35 wGA infants are indicated.
Hemorrhagic Plaques in Mild Carotid Stenosis: The Risk of Stroke

ABSTRACT: Objectives: Embolic ischemic strokes cause significant mortality and morbidity worldwide. It has been proposed that some of these strokes are due to unstable carotid plaques with intraplaque hemorrhage (IPH) but a low overall degree of stenosis. Our aim was to test a fat-saturated T1-weighted (T1WI) black-blood sequence on MRI for the detection of IPH in symptomatic individuals and to quantify the relation between IPH, severity of stenoses, and ischemic brain lesions. Materials and Methods: Sixty-two patients were examined by 3T MRI. Sequences included brain diffusion-weighted imaging (DWI) as well as 3D turbo spin echo (TSE) fat-saturated black-blood T1 of the carotid bifurcations, to detect IPH as a focal intraplaque hyperintensity. Both carotid arteries were analyzed in each patient. The North American Symptomatic Carotid Endarterectomy Trial scale was used for quantification of stenosis degree. Results: Thirty-six out of 62 patients (mean age, 74) showed brain ischemia on DWI. Fifteen of these 36 patients (42%) had associated ipsilateral IPH at the carotid bifurcation or the proximal internal carotid artery. Mean degree of stenosis in this group was 50%. In 21 patients with ischemia without IPH, the mean degree of stenosis was 44%. Conclusions: MRI with 3D TSE fat-saturated black-blood T1 technique is a safe, reliable, and noninvasive tool for the detection of IPH. A high percentage (42%) of ischemic events in patients with low- to moderate-degree stenosis were associated with IPH, an easily detectable imaging biomarker of plaque vulnerability. The ability to confirm IPH by MRI may help stratify patients into different risk and treatment groups in the future.
Relationships between Respiratory Quotient and Metabolic Rate during Entry to and Arousal from Daily Torpor in Deer Mice (Peromyscus maniculatus)

Retention of CO2 and respiratory acidosis have previously been reported to accompany entrance to hibernation, with acid-base and CO2 balance returning to normal upon arousal from hibernation. The present study indicates that these alterations are not limited to species which have the ability to undergo deep hibernation, but are also involved in another mammalian dormancy state, daily torpor. Deer mice (Peromyscus maniculatus) were used to examine the time course of changes in respiratory quotient (RQ), metabolic rate (MR), and body temperature (Tb) during daily torpor at an ambient temperature of 10° C For several hour sprior to daily torpor, RQ steadily declined from 0.92 to 0. 74, indicating a shift in primary metabolic substrate from carbohydrate to fat, while MR and Tb remained constant at 4.23 ± 0 44 mL O₂/g · h and 36.6° ± 0.9° C, respectively. Entrance to daily torpor involved a transitory decrease in RQ (0.74–0.63–0.73) that lasted less than 12 min and reflected CO2 retention and accompanying respiratory acidosis. This was subsequently followed by a rapid drop in MR and Tb. Respiratory quotient remained stable during steady-state torpor (0.74 ± 0.02). Metabolic rate and Tb in daily torpor were 1.12 ± 0.35 mL O2/g · h and 21.6° ± 1.6° C, respectively. A transitory increase in RQ (0.76–0.96–0.76) was associated with arousal, signifying release of the excess CO2, with MR and then Tb increasing after the RQ change. The order of change in the measured parameters suggests that adjustments in the CO2 content of the body contribute to the induction and termination of daily torpor in deer mice.
Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system as potential therapeutic targets. Therefore, the aim of this study was to evaluate the effects of long-term treatment with Ang-(1-7) in male Wistar rats with TLE induced by pilocarpine. Rats with TLE were submitted to intracerebroventricular infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein Bcl-2, as well as mTOR phosphorylation, which were reduced by TLE. The hippocampal upregulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor was downregulated compared to epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.
Wearable Active Electrode for sEMG Monitoring Using Two-Channel Brass Dry Electrodes with Reduced Electronics

Gel-based electrodes are employed to record sEMG signals for prolonged periods. These signals are used for the control of myoelectric prostheses, clinical analysis, or sports medicine. However, when the gel dries, the electrode-skin impedance increases considerably. Using dry active electrodes (AEs) to compensate variations of impedance is an alternative for long-term recording. This work describes the optimization of the electronic design of a conventional AE by removing the impedance coupling stage and two filters. The proposed work consisted of 5 stages: electrodes, amplification (X250), 2.2 Vdc offset, low-pass filter, and ADC with USART communication. The device did not need the use of electrolytic gel. The measurements of CMRR (96 dB), amplitude of the output sEMG signal (∼1.6 Vp-p), and system bandwidth (15–450 Hz) were performed in order to confirm the reliability of the device as an sEMG signal acquisition system. The SNR values from seven movements performed by eleven volunteers were compared in order to measure the repeatability of the measurements (average 30.32 dB for a wrist flexion). The SNR for wrist flexion measured with the proposed and the commercial system was compared; the values were 49 dB and 60 dB, respectively.
Do acute hepatopancreatic necrosis disease-causing PirABVP toxins aggravate vibriosis?

ABSTRACT Gram-negative marine bacterium Vibrio parahaemolyticus is an important aquatic pathogen and has been demonstrated to be the causative agent of acute hepatopancreatic necrotic disease (AHPND) in shrimp aquaculture. The AHPND-causing V. parahaemolyticus strains contain a pVA1 plasmid encoding the binary PirAVP and PirBVP toxins, are the primary virulence factor that mediates AHPND and mortality in shrimp. Since PirABVP toxins are secreted extracellularly, one can hypothesize that PirABVP toxins would aggravate vibriosis in the aquatic environment. To address this, in vivo and in vitro experiments were conducted. Germ-free Artemia franciscana were co-challenged with PirABVP toxins and 10 Vibrio spp. The in vivo results showed that PirABVP toxin interact synergistically with MM30 (a quorum sensing AI-2 deficient mutant) and V. alginolyticus AQ13-91, aggravating vibriosis. However, co-challenge by PirABVP toxins and V. campbellii LMG21363, V. parahaemolyticus CAIM170, V. proteolyticus LMG10942, and V. anguillarum NB10 worked antagonistically, increasing the survival of Artemia larvae. The in vitro results showed that the addition of PirABVP toxins significantly modulated the production of the virulence factors of studied Vibrio spp. Yet these in vitro results did not help to explain the in vivo results. Hence it appears that PirABVP toxins can aggravate vibriosis. However, the dynamics of interaction is strain dependent.