Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane Lipid Remodeling in Response to Salinity

Salinity is one of the most decisive environmental factors threatening the productivity of crop plants. Understanding the mechanisms of plant salt tolerance is critical to be able to maintain or improve crop yield under these adverse environmental conditions. Plant membranes act as biological barriers, protecting the contents of cells and organelles from biotic and abiotic stress, including salt stress. Alterations in membrane lipids in response to salinity have been observed in a number of plant species including both halophytes and glycophytes. Changes in membrane lipids can directly affect the properties of membrane proteins and activity of signaling molecules, adjusting the fluidity and permeability of membranes, and activating signal transduction pathways. In this review, we compile evidence on the salt stress responses of the major membrane lipids from different plant tissues, varieties, and species. The role of membrane lipids as signaling molecules in response to salinity is also discussed. Advances in mass spectrometry (MS)-based techniques have largely expanded our knowledge of salt-induced changes in lipids, however only a handful studies have investigated the underlying mechanisms of membrane lipidome regulation. This review provides a comprehensive overview of the recent works that have been carried out on lipid remodeling of plant membranes under salt treatment. Challenges and future perspectives in understanding the mechanisms of salt-induced changes to lipid metabolisms are proposed.
Maternal undernutrition aggravates renal tubular necrosis and interstitial fibrosis after unilateral ureteral obstruction in male rat offspring

Maternal undernutrition is known to reduce glomerular number but it may also affect tubulointerstitium, capillary density, and response to oxidative stress. To investigate whether the latter elements are affected, we examined the response to unilateral ureteral obstruction (UUO), an established model of renal tubulointerstitial fibrosis, in the kidney of offspring from control and nutrient restricted rats. Six-week old male offspring from rats given food ad libitum (CON) and those subjected to 50% food restriction throughout pregnancy (NR) were subjected to UUO for 7 days. Body weight was significantly lower in NR. Systolic blood pressure and blood urea nitrogen increased similarly in CON and NR after UUO. Tubular necrosis in the obstructed kidney, on the other hand, was more extensive in NR. Also, the collagen area, a marker of fibrosis, of the obstructed kidney was significantly increased compared with the contralateral kidney only in NR. Capillary density was decreased similarly in the obstructed kidney of CON and NR compared with the contralateral kidney. Urine nitrate/nitrite, a marker of nitric oxide production, from the obstructed kidney was significantly increased in NR compared with CON. Nitrotyrosine, a marker of nitric oxide-mediated free radical injury, was increased in the obstructed kidney compared with the contralateral kidney in both CON and NR, but the extent was significantly greater in NR. In conclusion, more severe tubular necrosis and fibrosis after UUO was observed in NR, which was thought to be due to increased nitrosative stress.
Polygenic selection drives the evolution of convergent transcriptomic landscapes across continents within a Nearctic sister-species complex

In contrast to the plethora of studies focusing on the genomic basis of adaptive phenotypic divergence, the role of gene expression during speciation has been much less investigated and consequently, less understood. Yet, the convergence of differential gene expression patterns between closely related species-pairs might reflect the role of natural selection during the process of ecological speciation. Here, we test for intercontinental convergence in differential transcriptional signatures between limnetic and benthic sympatric species-pairs of Lake Whitefish (Coregonus clupeaformis) and its sister-lineage, the European Whitefish (C. lavaretus), using six replicated sympatric species-pairs (two in North America, two in Norway and two in Switzerland). We characterized both sequence variation in transcribed regions and differential gene expression between sympatric limnetic and benthic species across regions and continents. Our first finding was that differentially expressed genes (DEG) between limnetic and benthic whitefish tend to be enriched in shared polymorphism among sister-lineages. We then used both genotypes and co-variation in expression in order to infer polygenic selection at the gene level. We identified parallel outliers and DEG involving genes primarily over-expressed in limnetic species relative to the benthic species. Our analysis finally revealed the existence of shared genomic bases underlying parallel differential expression across replicated species pairs from both continents, such as a cis-eQTL affecting the pyruvate kinase expression level involved in glycolysis. Our results are consistent with a longstanding role of natural selection in maintaining transcontinental diversity at phenotypic traits involved in ecological speciation between limnetic and benthic whitefishes.
Elucidating Compound Mechanism of Action and Predicting Cytotoxicity Using Machine Learning Approaches, Taking Prediction Confidence into Account

The modes of action (MoAs) of drugs frequently are unknown, because many are small molecules initially identified from phenotypic screens, giving rise to the need to elucidate their MoAs. In addition, the high attrition rate for candidate drugs in preclinical studies due to intolerable toxicity has motivated the development of computational approaches to predict drug candidate (cyto)toxicity as early as possible in the drug‐discovery process. Here, we provide detailed instructions for capitalizing on bioactivity predictions to elucidate the MoAs of small molecules and infer their underlying phenotypic effects. We illustrate how these predictions can be used to infer the underlying antidepressive effects of marketed drugs. We also provide the necessary functionalities to model cytotoxicity data using single and ensemble machine‐learning algorithms. Finally, we give detailed instructions on how to calculate confidence intervals for individual predictions using the conformal prediction framework. © 2019 by John Wiley & Sons, Inc.
Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Dysregulation of the chemokine system is implicated in a number of autoimmune and inflammatory diseases, as well as cancer. Modulation of chemokine receptor function is a very promising approach for therapeutic intervention. Despite interest from academic groups and pharmaceutical companies, there are currently few approved medicines targeting chemokine receptors. Monoclonal antibodies (mAbs) and antibody-based molecules have been successfully applied in the clinical therapy of cancer and represent a potential new class of therapeutics targeting chemokine receptors belonging to the class of G protein–coupled receptors (GPCRs). Besides conventional mAbs, single-domain antibodies and antibody scaffolds are also gaining attention as promising therapeutics. In this review, we provide an extensive overview of mAbs, single-domain antibodies, and other antibody fragments targeting CXCR4 and ACKR3, formerly referred to as CXCR7. We discuss their unique properties and advantages over small-molecule compounds, and also refer to the molecules in preclinical and clinical development. We focus on single-domain antibodies and scaffolds and their utilization in GPCR research. Additionally, structural analysis of antibody binding to CXCR4 is discussed. SIGNIFICANCE STATEMENT Modulating the function of GPCRs, and particularly chemokine receptors, draws high interest. A comprehensive review is provided for monoclonal antibodies, antibody fragments, and variants directed at CXCR4 and ACKR3. Their advantageous functional properties, versatile applications as research tools, and use in the clinic are discussed.
Inflammatory Dietary Pattern Predicts Dyslipidemia and Anemia in Middle-Aged and Older Taiwanese Adults with Declined Kidney Function: A Cross-Sectional Population Study from 2008 to 2010

Dyslipidemia, anemia, and inflammation are associated with declined kidney function. This study investigated the association of inflammatory dietary pattern with dyslipidemia, anemia, and kidney function biomarkers among middle-aged and older Taiwanese adults with declined kidney function. Biochemical data and food frequency questionnaire were obtained from 41,128 participants with estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and positive urinary protein. Inflammatory dietary pattern was identified by reduced rank regression with C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (N/L) as response variables. Males had higher prevalence of dyslipidemia and higher inflammatory markers, but lower prevalence of anemia and lower eGFR levels compared to females. Inflammatory dietary pattern characterized with low intakes of seafood, grains, vegetables, and fruits but high intakes of meat, eggs, preserved/processed foods, and sugary drinks was associated with an increased risk of dyslipidemia by 21% in males and an increased risk of anemia by 28–47% in both genders. Furthermore, high consumption of inflammatory dietary pattern was associated with reduced eGFR (males β = −0.85, 95% CI −1.26 to −0.43, females β = −0.53, 95% CI −0.98 to −0.08) and increased N/L and/or CRP in both genders. In conclusion, inflammatory dietary pattern is positively associated with dyslipidemia, anemia, and decreased kidney function in middle-aged and older adults with declined kidney function.
Dietary Behaviour Is Associated with Cardiometabolic and Psychological Risk Indicators in Female Hospital Nurses—A Post-Hoc, Cross-Sectional Study

Unfavourable dietary behaviours of female nurses, especially among shift-working nurses, including high snacking frequency, short fasting period and large day-to-day energy intake variability may be linked with adverse health. In this study we: (1) examined the relationship between dietary behaviour and cardiometabolic and psychological health in female nurses; and, (2) compared dietary behaviour, cardiometabolic and psychological health between shift-working and non-shift-working female nurses. A total of 73 nurses had their cardiometabolic health indicators evaluated and completed psychological health questionnaires; 55 completed a 3-day dietary log. Associations between dietary behaviour and health measures were examined using Spearman’s partial correlation analysis. Analysis of covariance (ANCOVA) was used to compare dietary behaviour and health indicators between shift- and non-shift-working nurses. The majority of snacks consumed by nurses (70%) were unhealthy snacks (e.g., chocolate and chips), and higher snacking frequency was associated with greater percent body fat (r(50) = 0.287, p = 0.039), and worse mood-tension (r(48) = 0.327, p = 0.021) and anger-hostility (r(48) = 0.289, p = 0.042) scores. Day-to-day energy intake variability was positively associated with body mass index (BMI, r(50) = 0.356, p = 0.010) and waist circumference (r(50) = 0.283, p = 0.042). Shift-working nurses exhibited shorter fasting duration, larger day-to-day energy intake variability and higher total mood disturbance score when compared to their non-shift-working colleagues (all p < 0.05). The results of the present study suggested that addressing dietary behaviours may improve the cardiometabolic and psychological health of female nurses. Shift-working nurses may require a more specific dietary program to improve their psychological health.
Impact of disease risk on the narrative bias in vaccination risk perceptions

Abstract Objective: Previous studies have shown that even when a statistical base-rate of vaccine adverse events (VAE) is provided, a small sample of single-case narratives influences vaccination risk perceptions and vaccination intentions, irrespective of various content characteristics. This study investigated whether this narrative bias is moderated by an environmental feature, namely the risk of the disease. Design: In three online-experiments, 564 subjects were presented with statistical information (20%) about the probability of VAE associated with a hypothetical vaccination and with a sample of narratives describing personal vaccination experiences. The relative frequency of narratives reporting VAE was varied between-subjects (5/20/35%) to test for a bias. Three potential moderators were tested: likelihood of infection, severity of disease and perceived susceptibility to the disease. Main outcome measures: Perceived risk of vaccination and intention to get vaccinated. Results: Compared to the control condition (20%), narratives reporting VAE increased (35%) and decreased (5%) risk perceptions, which affected vaccination intentions respectively. This bias was not affected by any variable pertaining to the disease risk. Conclusion: People’s vaccination decisions are reliably affected by small samples of single-case vaccination experiences. As this influence works in either direction, health communicators should provide people with many examples of safely completed vaccinations.
Single-Molecule Analysis of Reverse Transcriptase Enzymes.

SUMMARYThe original discovery of enzymes that synthesize DNA using an RNA template appeared to contradict the central dogma of biology, in which information is transferred, in a unidirectional way, from DNA genes into RNA molecules. The paradigm-shifting discovery of RNA-dependent DNA polymerases, also called reverse transcriptases (RTs), reshaped existing views for how cells function; however, the scope of the impact RTs impose on biology had yet to be realized. In the decades of research since the early 1970s, the biomedical and biotechnological significance of retroviral RTs, as well as the evolutionarily related telomerase enzyme, has become exceedingly clear. One common theme that has emerged in the course of RT-related research is the central role of nucleic acid binding and dynamics during enzyme function. However, directly interrogating these dynamic properties is challenging because of the stochastic properties of biological macromolecules. In this review, we describe how the development of single-molecule biophysical techniques has opened new windows through which to observe the dynamic behavior of this remarkable class of enzymes. Specifically, we focus on how the powerful single-molecule Förster resonance energy transfer (FRET) method has been exploited to study the structure and function of the human immunodeficiency virus (HIV) RT and telomerase ribonucleoprotein (RNP) enzymes. These exciting studies have refined our understanding of RT catalysis, have revealed unforeseen structural rearrangements between RTs and their nucleic acid substrates, and have helped to characterize the mode of action of RT-inhibiting drugs. We conclude with a discussion of how the ongoing development of single-molecule technologies will continue to empower researchers to probe RT mechanisms in new and exciting ways.
The association between glycated albumin, glycohemoglobin, and glycated albumin to glycohemoglobin ratio in diabetic retinopathy of prediabetes

Prediabetes increased risk of diabetes and diabetes‐related macrovascular and microvascular complication. Glycohemoglobin (HbA1c) is clinically used as the gold standard for glycemic control of diabetes. Glycated albumin (GA) is an early Amadori‐type glycation protein between glucose and serum albumin, which changes in a shorter period of time than HbA1c and is superior to HbA1c in reflecting fluctuations in blood glucose. In this study, we aim to assess the predictive value of GA and glycohemoglobin (HbA1c) on a progression of diabetic retinopathy (DR) in prediabetic patients in Taiwan. This study was conducted at the outpatient department of a regional hospital in Southern Taiwan, and recruited 291 patients with prediabetes from January 2016 to February 2017. Blood and urine samples were obtained from all patients after fasting for 12 hours within 1 month of enrollment. The mean age is 62.5 ± 13.0 years and there are 161 males and 130 females. A total of 24.1% of patients have DR. The average value of GA and HbA1c are 14.6% ± 2.8% and 6.0% ± 0.4%, respectively. Old age, male, high systolic blood pressure, high HbA1C, and low total cholesterol are significantly associated with DR in patients with pre‐DM. Therefore, in the prediabetic populations, high HbA1C, but not GA nor GA/HbA1C ratio, is significantly associated with DR.
Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development.

The transcription factor B Cell CLL/Lymphoma 11B (BCL11B) is indispensable for T lineage development of lymphoid progenitors. Here we show that chimeric antigen receptor (CAR) expression early in ex vivo generated lymphoid progenitors suppressed BCL11B, leading to suppression of T cell-associated gene expression and acquisition of natural killer (NK) cell-like properties. Upon adoptive transfer into hematopoietic stem cell transplant recipients they differentiated into CAR-induced killer cells (CARiK) that mediated potent antigen-directed antileukemic activity even across MHC barriers. A CD28 and active immune-receptor-tyrosine-based-activation-motifs were critical for a functional CARiK phenotype. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene-expression and encourage further evaluation of ex vivo generated CARiK cells for targeted immunotherapy.
[Treatment with bisphosphonates improves the quality of life in patients with diagnosis of osteogenesis imperfecta].

INTRODUCTION Osteogenesis imperfeta (OI) is defined as a heterogeneous group of hereditary diseases, which present with the presence of bone fragility, frequent fractures, bone deformities and short stature. Treatment with biphosfonates in patients with diagnosis of OI has shown a decrease in the frecuency of fractures, as well as an improvement in vertebral bone density. There is little evidence on quality of life in patients diagnosed with OI treated with bisphosphonates, Therefore this study evaluated the quality of life of patients diagnosed with OI after treatment with bisphosphonates. MATERIAL AND METHODS It is a prospective, deliberate intervention, self-controlled clinical trial. Nine patients with ages between two and thirteen ages and diagnosed with OI were treated with Zolendronic, a quality of life measurement was performed in the patients before and after the application. For measuring the quality of life in the patients we used the PedsQL 4.0 quality of life survey that was applied to both children and parents. RESULTS In the quality of life survey performed on the parents, an increase was observed in the four dimensions evaluated. In the survey made on the children two dimensions showed a significant increase. The number of fractures decreased after the treatment. CONCLUSIONS There is a correlation between the decrease in the number of fractures and the perception that both parents and children have in the quality of life after treatment with bisphosphonates.
Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide. However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking. Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection. Samples of patients with hematologic malignancies, solid tumors, or sickle cell disease were included. Clinical information from institutional medical records was reviewed to assess disease severity. Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients. Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively. RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age. Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy. Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.
Sound pressure levels in classrooms of a University and its effects on students and professors

Accepted: December 12, 2018 Study conducted at Departamento de Fonoaudiologia, Pontifícia Universidade Católica de Minas Gerais – PUC Minas Belo Horizonte (MG), Brasil. 1 Departamento de Fonoaudiologia, Pontifícia Universidade Católica de Minas Gerais – PUC Minas Belo Horizonte (MG), Brasil. 2 Pontifícia Universidade Católica de Minas Gerais – PUC Minas Belo Horizonte (MG), Brasil. Financial support: nothing to declare. Conflict of interests: nothing to declare. ABSTRACT
Does Improvement of Low Serum Ferritin Improve Symptoms of Restless Legs Syndrome in a Cohort of Pediatric Patients?

STUDY OBJECTIVES To determine whether an oral iron supplement improves restless leg/restless sleep symptoms in a pediatric population. METHODS In a cohort study, 47 patients (age 5-18 years) exhibiting restless legs/restless sleep symptoms and low serum ferritin levels (< 50 ng/mL) were given a daily oral iron supplement (ferrous sulfate + vitamin C) and re-evaluated 8 weeks later. A diagnosis of definite Restless Legs Syndrome (RLS) was determined based on criteria established by the International RLS Study Group. Using Wilcoxon signed-rank tests and Spearman rho, the change and association between the measures of Pediatric Restless Legs Syndrome Severity Scale and serum ferritin levels were also examined. RESULTS Overall, the median change and distribution of ferritin was statistically significantly different after 8 weeks of treatment (40.0 versus 23.0 ng/mL, P < .0001). Median RLS score was also statistically significantly lower from baseline to follow-up (4.0 versus 6.0, P = .0283). Sixteen patients met criteria for definite RLS; however, the change in RLS score was not determined to be significant in our population (9.5 versus 7.0, P = .0558), despite significant change in ferritin (25.0 versus 42.5 ng/mL, P < .0001). In addition, no correlation was observed between change in RLS score and ferritin level (rho = -.39, P = .1362). CONCLUSIONS In preliminary findings, we found a modest, yet nonsignificant improvement in children exhibiting restless sleep and RLS symptomatology, despite significant improvement in ferritin levels. Though not statistically significant, the findings can lend to the suggested benefit of iron supplementation in patients with RLS; however, clinical judgment and further research is necessary. CITATION Rosen GM, Morrissette S, Larson A, Stading P, Barnes TL. Does improvement of low serum ferritin improve symptoms of restless legs syndrome in a cohort of pediatric patients? J Clin Sleep Med. 2019;15(8):1149-1154.