Miracle-dz/UniFAR-FTUs huggingface dataset:
Transposons played a major role in the diversification between the closely related almond and peach genomes: results from the almond genome sequence

Summary We sequenced the genome of the highly heterozygous almond Prunus dulcis cv. Texas combining short‐ and long‐read sequencing. We obtained a genome assembly totaling 227.6 Mb of the estimated almond genome size of 238 Mb, of which 91% is anchored to eight pseudomolecules corresponding to its haploid chromosome complement, and annotated 27 969 protein‐coding genes and 6747 non‐coding transcripts. By phylogenomic comparison with the genomes of 16 additional close and distant species we estimated that almond and peach (Prunus persica) diverged around 5.88 million years ago. These two genomes are highly syntenic and show a high degree of sequence conservation (20 nucleotide substitutions per kb). However, they also exhibit a high number of presence/absence variants, many attributable to the movement of transposable elements (TEs). Transposable elements have generated an important number of presence/absence variants between almond and peach, and we show that the recent history of TE movement seems markedly different between them. Transposable elements may also be at the origin of important phenotypic differences between both species, and in particular for the sweet kernel phenotype, a key agronomic and domestication character for almond. Here we show that in sweet almond cultivars, highly methylated TE insertions surround a gene involved in the biosynthesis of amygdalin, whose reduced expression has been correlated with the sweet almond phenotype. Altogether, our results suggest a key role of TEs in the recent history and diversification of almond and its close relative peach.
A Comparison of Coronary Artery Stenosis Estimates Made by Forensic Pathologists and Medical Students

Previous studies suggest cardiovascular pathologists are less accurate than noncardiovascular pathologists (e.g., clinical pathologists) in estimating the degree of coronary artery stenosis. To further investigate the effect of training on accurate estimation of coronary artery stenosis, we designed a study to compare the accuracy of estimates made by forensic pathologists versus medical students. Six forensic pathologists and twelve medical students each independently examined 24 images of coronary artery cross sections and gave an estimate of the degree of stenosis. When comparing all 24 images, the forensic pathologists had a median difference between the estimated percentage of stenosis and actual percentage of stenosis of −12.380 and the medical students had a median difference of −16.50 (p‐value of 0.08542). In estimating the percentage of stenosis, training in forensic pathology does not guarantee significantly improved accuracy compared with medical students. Our study showed no consistent statistically significant difference between estimates given by forensic pathologists and by medical students.
Failure to identify modifiers of NEBULIN-related nemaline myopathy in two pre-clinical models of the disease

ABSTRACT Nemaline myopathy is a rare neuromuscular disorder that affects 1 in 50,000 live births, with prevalence as high as 1 in 20,000 in certain populations. 13 genes have been linked to nemaline myopathy (NM), all of which are associated with the thin filament of the muscle sarcomere. Of the 13 associated genes, mutations in NEBULIN (NEB) accounts for up to 50% of all cases. Currently, the disease is incompletely understood and there are no available therapeutics for patients. To address this urgent need for effective treatments for patients affected by NM, we conducted a large scale chemical screen in a zebrafish model of NEB-related NM and an N-ethyl-N-nitrosourea (ENU)-based genetic screen in a mouse model of NEB exon 55 deletion, the most common NEB mutation in NM patients. Neither screen was able to identify a candidate for therapy development, highlighting the need to transition from conventional chemical therapeutics to gene-based therapies for the treatment of NM. Summary: NEBULIN-related nemaline myopathy currently has no treatment. We attempted to uncover new avenues for therapy by performing modifier screens, which unfortunately failed to identify modifiers that improved disease relevant phenotypes.
Inhibitory learning of phototaxis by honeybees in a passive-avoidance task

Honeybees are a standard model for the study of appetitive learning and memory. Yet, fewer attempts have been performed to characterize aversive learning and memory in this insect and uncover its molecular underpinnings. Here, we took advantage of the positive phototactic behavior of bees kept away from the hive in a dark environment and established a passive-avoidance task in which they had to suppress positive phototaxis. Bees placed in a two-compartment box learned to inhibit spontaneous attraction to a compartment illuminated with blue light by associating and entering into that chamber with shock delivery. Inhibitory learning resulted in an avoidance memory that could be retrieved 24 h after training and that was specific to the punished blue light. The memory was mainly operant but involved a Pavlovian component linking the blue light and the shock. Coupling conditioning with transcriptional analyses in key areas of the brain showed that inhibitory learning of phototaxis leads to an up-regulation of the dopaminergic receptor gene Amdop1 in the calyces of the mushroom bodies, consistently with the role of dopamine signaling in different forms of aversive learning in insects. Our results thus introduce new perspectives for uncovering further cellular and molecular underpinnings of aversive learning and memory in bees. Overall, they represent an important step toward comparative learning studies between the appetitive and the aversive frameworks.
Sense of coherence and physical health–related quality of life in Italian chronic patients: the mediating role of the mental component

Objective To examine the relationship between sense of coherence (SOC) and physical health–related quality of life in patients with chronic illnesses by focusing on the mediating role of the mental component of quality of life. Design Cross-sectional survey design. Setting Secondary care; three departments of an Italian university hospital. Methods The participants (n=209) in the study were adult (≥18 years) outpatients with a chronic pathology (eg, diabetes, thyroid disorders or cancer) at any phase in the care trajectory (eg, pre-treatment, undergoing treatment, follow-up care). They agreed to participate in the study after providing their informed consent. Data were collected using a structured self-reporting questionnaire. Data analysis was carried out using SPSS, and mediation analysis was performed via PROCESS macro. Results The SOC score of the study sample was equivalent to that of the general population (mean difference=−2.50, 95% CI −4.57 to 0.00). Correlation analysis showed that SOC was mainly correlated to the mental component (MCS) (r=0.51, p<0.01) of quality of life and then to the physical component (PCS) (r=0.35, p<0.01). Mediation analysis showed that SOC was directly related to MCS (p<0.001, 95% CI 0.62 to 0.99) but not to PCS (p=0.42, 95% CI −0.27 to 0.12). In turn, MCS was directly related to PCS (p<0.001, 95% CI 0.76 to 1.01). The indirect effect of SOC on PCS through MCS was significant (0.71, p<0.001, bootstrap 95% CI 0.54 to 0.91), thus supporting the mediating role of the mental component of quality of life. Conclusion The indirect effect suggests that SOC is a marker of quality of life, especially of the mental component. The findings show that SOC is a psychological process that impacts patients’ mental health status, which in turn affects physical health. Better knowledge of a person’s SOC and how it affects his/her quality of life may help to plan tailoring interventions to strengthen SOC and improve health-related quality of life.
Cytokinin signaling coordinates development of diverse organs in Marchantia polymorpha

ABSTRACT Cytokinins play an essential role in plant growth and development. A recent study showed that the cytokinin signaling pathway was conserved in the liverwort Marchantia polymorpha, and that it controlled gemma cup and rhizoid formation during thallus development. Here we show that the type-B response regulator, MpRRB, is mainly localized in the nucleus. Moreover, observations of thalli revealed that the distribution of air pores and the shape of the thallus margin are impaired in cytokinin-deficient lines and those defective in cytokinin signaling. This suggests that cytokinins regulate cell division and/or differentiation of precursor cells derived from the apical cell, thereby coordinating development of various organs produced on the thallus.
Management of nursing care in HIV/AIDS from a palliative and hospital perspective.

OBJECTIVES To understand the meaning attributed by the nurse to the management of nursing care to the person hospitalized due to clinical complications caused by AIDS; to analyze actions related to palliative care; and to construct a theoretical matrix regarding the management of nursing care. METHOD Qualitative, exploratory research, guided by the Grounded Theory. Seven nurses and ten nursing technicians were interviewed between May and September 2015, in a university hospital, located in Rio de Janeiro State, Brazil. RESULTS Five categories that covered the profile of the hospitalized person, palliative care, intervening conditions for care management, the need for professional qualification, and other aspects to better organize and manage care, including conflict management arose. FINAL CONSIDERATIONS The theoretical matrix values the quality of life, the need to understand the flow of care to avoid readmissions and not adherence to medications, requiring new research in the area, such as implementation.
Serum 1,5-Anhydroglucitol Concentration as a Biomarker for Type 1 Diabetes in Adults and Children.

BACKGROUND Type 1 diabetes (T1D) is an autoimmune disease and the leading form of diabetes among young white people. 1,5-Anhydroglucitol (1,5-AG), a nontraditional biomarker of postprandial glycemic control (after 1 - 3 days to 2 weeks), may be useful in T1D screening. We studied serum 1,5-AG concentration as a potential biomarker for T1D screening and diagnosis in adults and children. METHODS In this case-control study, adults (n = 121; age, 19 - 61 years) and children (n = 19; age, 8 - 14 years) with T1D were matched with healthy subjects (n = 242) according to gender and age. Serum 1,5-AG levels were measured enzymatically (GlycoMark Inc., NY, USA). RESULTS Patients showed no symptoms of overt kidney disease, assessed by serum creatinine concentrations. The median (25th - 75th percentile) 1,5-AG concentrations for the control group compared with the T1D group were 155 (128 - 183) vs. 21 (14 - 34) µmol/L in adults and 190 (158 - 237) vs. 20 (12 - 30) µmol/L in children (p < 0.001 for both). Receiver operating characteristic curves showed that 1,5-AG cutoffs of ≤ 113 and ≤ 79 µmol/L for adult men and women, respectively, and ≤ 57 µmol/L for children of both genders had > 95% sensitivity and specificity for both groups. CONCLUSIONS Our results suggest that serum 1,5-AG concentration may be useful as an adjunct measure of hyperglycemia for diagnosing T1D and has the potential to screen for T1D in high-risk subjects.
Effects of exogenous glucose on Pseudomonas aeruginosa biofilm formation and antibiotic resistance

Pseudomonas aeruginosa is commonly found in nosocomial and life‐threatening infections in patients. Biofilms formed by P. aeruginosa exhibit much greater resistance to antibiotics than the planktonic form of the bacteria. Few groups have studied the effects of glucose, a major carbon source, and metabolite, on P. aeruginosa biofilm formation and on its metabolic pathways. In this study, we investigated the effect of glucose on the biofilm formation ability of P. aeruginosa and carried out a metabolomic analysis to identify whether glucose alters the metabolic activity of P. aeruginosa in biofilms. We found that glucose efficiently promoted P. aeruginosa biofilm formation by upregulating the expression of the extracellular polysaccharide‐related gene pslA. Treatment with glucose caused an increase in 7 metabolites (including 3‐hydroxypropionic acid, glucose‐6‐phosphate, and 2,3‐dimethylsuccinic acid) and a decrease in 18 metabolites (including myo‐inositol, glutamine, and methoxamedrine) in the biofilm. In addition, there was a synergistic effect between glucose and horse serum on biofilm formation when the two were added in combination, which also increased the resistance of biofilm to levofloxacin therapy. Thus, our work sheds light on the underlying mechanisms by which glucose may enhance biofilm formation and identifies novel targets for developing strategies to counteract biofilm formation.
Immunological Analysis of a CCHFV mRNA Vaccine Candidate in Mouse Models

Development of new vaccine platforms against viral diseases is considered urgent. In recent years, mRNA constructs have attracted great interest in this field due to unique advantages over conventional gene transfer platforms. In the present study, we developed a new naked conventional mRNA vaccine expressing the non-optimized small (S) segment of the Ank-2 strain of Crimean-Congo Hemorrhagic Fever virus (CCHFV). We then analyzed its single and booster dose immunogenicity and protection potential in the challenge assay in two mice models, including IFNα/β/γR−/− and C57BL/6. The results obtained from the immunological assays, namely IL-4 and IFN-gamma ELISPOT, intracellular IFN-gamma staining, in-house sandwich ELISA, and survival data, demonstrated that our construct elicited the production of anti-nucleocapsid (N) specific immune responses in both mice models. A 100% protection rate was only obtained in the booster dose group of IFNα/β/γR−/− mice, indicating that this platform needs further optimization in future studies. In conclusion, we assessed a novel approach in CCHFV vaccination by introducing a conventional mRNA platform which can be considered in future experiments as an efficient and safe way to battle this disease.
Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention.

Insulin resistance has wide-ranging effects on metabolism but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns, and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ~45% of V̇O2peak, ~63 W) and recovery in overnight-fasted sedentary, obese, insulin resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ~14 wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise-regardless of pre- vs. post-intervention status-highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of non-oxidative fates of glucose (e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside [possible glycerolipid synthesis metabolite]), and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites ("non-self" molecules, from microbes or foods), including benzoic acid/salicylic acid/salicylaldehyde, hexadecanol/octadecanol/dodecanol, and chlorogenic acid. In addition, many non-annotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results, and previously-reported plasma acylcarnitine profiles, support the principle that most metabolic changes during sub-maximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.
N-Acetyl Cysteine attenuates the sarcopenia and muscle apoptosis induced by chronic liver disease.

Sarcopenia is characterized by the loss of muscle mass and strength (muscle atrophy) because of aging or chronic diseases such as chronic liver disease (CLD). Different mechanisms are involved in skeletal muscle atrophy, including decreased muscle fibre diameter and myosin heavy chain levels and increased ubiquitin-proteasome pathway activity, oxidative stress and myonuclear apoptosis. We recently found that all these mechanisms, except myonuclear apoptosis, which was not evaluated in the previous study, were involved in muscle atrophy associated with hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD. In the present study, we evaluated the involvement of myonuclear apoptosis in CLD-associated sarcopenia and the effect of N-acetyl cysteine (NAC) treatment on muscle strength and apoptosis, using a DDC-supplemented diet-fed mouse model. Four-month-old male C57BL6 mice were fed a standard or DDC-supplemented diet for six weeks in the absence or presence of NAC treatment. Our results showed that NAC attenuated the decrease in muscle fibre diameter and muscle strength associated with CLD-induced muscle wasting in gastrocnemius (GA) muscle of DDC-supplemented diet-fed mice. In addition, in GA muscle of the mice with DDC-supplemented diet-induced CLD showed increased myonuclear apoptosis compared with the GA muscle of the control diet-fed mice, as evidenced by increased apoptotic nuclei number, caspase-8 and caspase-9 expression, caspase-3 activity and BAX/BCL-2 ratio. NAC treatment inhibited all the mechanisms associated with myonuclear apoptosis in the GA muscle. To our knowledge, the present study is the first to report the redox regulation of muscle strength and myonuclear apoptosis in CLD-induced sarcopenia.
Associations between birth order with mental wellbeing and psychological distress in midlife: Findings from the 1970 British Cohort Study (BCS70)

Background Previous research indicated that birth order was associated with physical health outcomes in adulthood. However, evidence on its association with mental health was lacking. The aim of this study was to investigate if birth order was associated with mental wellbeing and psychological distress at mid-life, stratified by gender, and taking into account confounding factors in childhood and adulthood. Method The sample consisted of 9,354 participants of the 1970 British Cohort Study (BCS70). The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), the Malaise Index and attending a doctor’s consultation in the past year for a mental health issue at age forty-two were used to assess mental wellbeing and psychological distress in midlife. Birth order was ascertained via a parental questionnaire and referred to the numerical birth position of the participants. The associations between birth order, mental wellbeing and psychological distress were tested using linear and logistic regression adjusting for birth characteristics: smoking during pregnancy, maternal age, mother’s marital status, father’s employment, region of birth, parental years of education and parental social class, and factors at age 42: years of education, employment status and partnership status. Potential mediating variables including breastfeeding and birthweight at birth and parental separation and conduct disorder measured at age ten were also taken into account. Results We find no evidence to support an association between birth order and midlife psychological distress or attending a doctor’s consultation in both men and women. In unadjusted analysis, there was an association between birth order four and above and a reduced WEMWBS score of -0.79 (95% CI -1.57, -0.02) in men only. This association was attenuated after adjusting for birth characteristics and mediators at birth (0.86, 95% -1.78, 0.07) but was maintained once conduct disorder at age 10 was accounted for (-1.19, 95% CI -2.28, -0.09). However, this association was attenuated once again after adjusting for employment status, years in education and partnership status in adulthood (-1.04, 95% CI -2.11, 0.03). Conclusions In this study, birth order was not associated with psychological distress or having a mental health issue at midlife. Accounting for employment status, years of education and partnership status in adulthood attenuated the relationship between birth order and mental wellbeing.
Ni(HCO3)2 nanosheet/nickel tetraphosphate (Ni(P4O11)) nanowire composite as a high-performance electrode material for asymmetric supercapacitors

Nickel compounds, especially Ni(HCO3)2 (here denoted as NiC), have been widely combined with other materials to obtain composites with a more favorable structure that exhibit excellent electrochemical performance as supercapacitors. Unfortunately, the complicated processes for preparing such composites directly restrict their further application. Herein, we prepared a NiC/nickel tetraphosphate (Ni(P4O11)) nanocomposite (NiC/NiP) by introducing H 2 PO 4 − ions into the NiC reaction system; this composite can be applied in high-performance supercapacitors. The micromorphology of NiC/NiP material displayed an appropriate combination of NiP nanowires and thin NiC nanosheets, which provide sufficient active sites, short ion diffusion paths and fast ion diffusion speeds. NiC/NiP material exhibited an excellent rate performance of 70.2% retained capacity, although the current was increased by 15 times (1196 F g−1 at 2.0 A g−1 and 840 F g−1 at 30 A g−1). The energy density of a NiC/NiP//active carbon (AC) asymmetric supercapacitor fabricated in 6 M KOH was as much as 39.02 W h kg−1 and 26.67 W h kg−1 under corresponding power densities of 160 W kg−1 and 8000 W kg−1, respectively. The asymmetric supercapacitor delivered a stable cyclic performance of 78% capacitive retention after 5000 continuous charge/discharge cycles. More importantly, a 2.5 V light-emitting diode was lit successfully by two NiC/NiP//AC asymmetric supercapacitors in series. These results confirm that NiC/NiP nanocomposite has great potential in practical applications of electrochemical energy storage devices.