Miracle-dz/UniFAR-FTUs huggingface dataset:
Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline

In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age‐related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse. Similar to the tandemly repeated rDNA, methylation of human α‐satellite and interspersed LINE1 repeats, marmoset α‐satellite, bovine alpha‐ and testis satellite I, mouse minor and major satellite, and LINE1‐T repeats increases in the aging male germline, probably related to their sperm histone packaging. Deep bisulfite sequencing of single rDNA molecules in human sperm revealed that methylation does not only depend on donor's age, but also depend on the region and sequence context (A vs. G alleles). Both average rDNA methylation of all analyzed DNA molecules and the number of fully (>50%) methylated alleles, which are thought to be epigenetically silenced, increase with donor's age. All analyzed CpGs in the sperm rDNA transcription unit show comparable age‐related methylation changes. Unlike other epigenetic aging markers, the rDNA clock appears to operate in similar ways in germline and soma in different mammalian species. We propose that sperm rDNA methylation, directly or indirectly, influences nucleolar formation and developmental potential in the early embryo.
Neurophysiological Correlate of Emotion Regulation by Cognitive Reappraisal and Its Association With Psychotic Symptoms in Early Psychosis.

BACKGROUND Emotion dysregulation is crucial to both poor social functioning and psychotic symptom formation in patients with schizophrenia. The efficient use of emotion regulation strategies, such as cognitive reappraisal, has been less frequently observed in the early phases of psychotic disorder. It is unknown whether neurophysiological responses related to emotion regulation by cognitive reappraisal are altered in early psychosis. METHODS Fifty-four patients with first-episode psychosis (FEP), 34 subjects at clinical high risk (CHR) for psychosis, and 30 healthy controls (HCs) participated in event-related potential recordings during a validated emotion regulation paradigm to measure the effect of cognitive reappraisal on emotion regulation. Late positive potentials (LPPs), which reflect emotional arousal, were compared across the groups and the 3 conditions (negative, cognitive reappraisal, and neutral). The relationship among LPP modulation by cognitive reappraisal and social/role functioning and severity of psychotic symptoms was investigated in the early psychosis group. RESULTS The FEP and CHR participants showed comparably larger LPP amplitudes in the negative and cognitive reappraisal conditions than in the neutral condition, whereas the HCs presented larger LPPs in the negative condition than in the cognitive reappraisal and neutral conditions. LPP modulation by cognitive reappraisal was negatively correlated with positive symptom severity in the FEP patients and with disorganization severity in the CHR subjects. CONCLUSIONS Inefficient use of cognitive reappraisal may be related to the impaired emotion regulation and psychotic symptoms from the very beginning of psychotic disorder. This study provides the first neurophysiological evidence regarding current concepts of emotion regulation in early psychosis.
Hemocyte production in Biomphalaria glabrata snails after exposure to different Schistosoma mansoni infection protocols

The objective of this work was to determine the profile of the cellular defense system during mansonic infection. Specifically, this study assessed the number of hemocytes that were produced and released into the hemolymph in response to the parasitic infection. The quantification of the Biomphalaria glabrata hemocytes was performed on groups of snails at 1, 5, 10, 15, 20 and 30 days post-infection that had been individually infected with 5, 10, 15 or 30 Schistosoma mansoni miracidia. The results revealed that B. glabrata possesses a cellular defense mechanism that is characterized by the release of hemocytes into the hemolymph. The maximum peak of cellular production occurred 24 hours after infection, and there was a significant reduction in the hemocyte concentration over the following 10 days. However, at 15 days post-infection, there was a second increase in the cellular hemocyte production, although this was not as strong as the primary peak. At 30 days post-infection, there was another moderate rise in the cellular hemocyte production. Based on this cellular response profile, the defense system of the snail appears to be effective immediately following infection, but the response does not ensure the destruction of all parasites during the course of the infection.
Recombinant zoster vaccine (Shingrix): a new option for the prevention of herpes zoster and postherpetic neuralgia

Postherpetic neuralgia (PHN), a serious complication after varicella zoster virus (VZV) infection, is a challenging neuropathic pain for pain management specialists [1,2]. This peripheral neuropathy can present as any one of three subtypes: continuous burning pain; paroxysmal shooting or electric shock-like pain; or evoked sensations such as mechanical allodynia, mechanical hyperalgesia, or an exaggerated response to light touch [3]. The burden of this illness increases with advancing patient age as a result of declining cell-mediated immunity [4]. This crippling condition can have an enormous negative impact on patient quality of life and their capacity to perform day to day activities. Severe symptoms of PHN cause sleep disturbance, fatigue, and depression, diminish personal satisfaction, and carry a general weight to family and society [3]; therefore, various modalities are used to relieve these symptoms [5]. In the United States (US), 10%-18% of herpes zoster (HZ) patients develop PHN and 68% of HZ and 85% of PHN patients are over 50 years of age and unable to endure the pain of PHN or associated symptoms [6]. The risk of HZ is 8-10 times greater after 50 years of age compared to that of younger ages [2]. A higher occurrence of HZ has been observed in patients with diabetes mellitus [7] and compromised immunity, particularly those with diseases Review Article
Characterization of Hspb8 in Zebrafish

Hspb8 is a member of the small heat shock protein (sHSP) family. Its expression is known to be upregulated under heat shock. This protein interacts with different partners and can, therefore, be involved in various processes relevant to tissue integrity and functioning. In humans, mutations in the gene encoding Hspb8 can lead to the development of various diseases such as myopathies and neuropathies. In our study, we aimed to perform an in-depth characterization of zebrafish Hspb8 during zebrafish development. We applied techniques such as RT-qPCR, Western blot, immunofluorescence, co-immunoprecipitation, LC-MS, and morpholino-mediated knockdown. We broadened the knowledge regarding zebrafish hspb8 expression during development under normal and heat shock conditions as well as its tissue- and subcellular-specific localization. A co-IP analysis allowed us to conclude that zebrafish Hspb8 can interact with proteins such as Bag3 and Hsc70, which are crucial for formation of an autophagy-inducing complex. We also demonstrated that hspb8 morpholino-mediated knockdown has an impact on zebrafish embryos’ morphology, muscle ultrastructure, and motility behavior. Our research provides a valuable resource for the potential use of the zebrafish as a model for studying pathological conditions associated with hspb8 disorders.
The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation

Significance Malaria kills ∼0.4 million people a year. Malaria parasite infection triggers complex immune responses that may control the infection or result in severe disease. The molecular mechanisms underlying host–parasite interaction and immune regulation are not completely understood. We perform a genome-wide genetic screen during early Plasmodium yoelii infection in mice and identify a large number of host and parasite genes/loci for future studies of the complex host–parasite interactions. We next investigate the functions of one of these host genes that encodes an E3 ubiquitin ligase (MARCH1). We show that MARCH1 regulates type I interferon signaling, T cell activation, and IFN-γ production during malaria infections. MARCH1 is a key molecule in immune responses and a potential target for immunotherapies. Malaria infection induces complex and diverse immune responses. To elucidate the mechanisms underlying host–parasite interaction, we performed a genetic screen during early (24 h) Plasmodium yoelii infection in mice and identified a large number of interacting host and parasite genes/loci after transspecies expression quantitative trait locus (Ts-eQTL) analysis. We next investigated a host E3 ubiquitin ligase gene (March1) that was clustered with interferon (IFN)-stimulated genes (ISGs) based on the similarity of the genome-wide pattern of logarithm of the odds (LOD) scores (GPLS). March1 inhibits MAVS/STING/TRIF-induced type I IFN (IFN-I) signaling in vitro and in vivo. However, in malaria-infected hosts, deficiency of March1 reduces IFN-I production by activating inhibitors such as SOCS1, USP18, and TRIM24 and by altering immune cell populations. March1 deficiency increases CD86+DC (dendritic cell) populations and levels of IFN-γ and interleukin 10 (IL-10) at day 4 post infection, leading to improved host survival. T cell depletion reduces IFN-γ level and reverse the protective effects of March1 deficiency, which can also be achieved by antibody neutralization of IFN-γ. This study reveals functions of MARCH1 (membrane-associated ring-CH–type finger 1) in innate immune responses and provides potential avenues for activating antimalaria immunity and enhancing vaccine efficacy.
Hyaluronic acid versus dexamethasone for the treatment of recurrent aphthous stomatitis in children: efficacy and safety analysis

The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.
Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines

Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix®, RotaTeq®, Rotavac®, and RotaSIIL®) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines.
Population decline of Leach’s Storm-petrel Oceanodroma leucorhoa within the largest colony in Britain and Ireland

This study used diurnal playback of vocalisations to examine the abundance of breeding Leach’s Storm-petrel Oceanodroma leucorhoa on Dun, St Kilda in 2003 and 2006 in relation to the only previous survey conducted using similar methodology in 1999. The number of Apparently Occupied Sites in 2006 was 12,770, not significantly different to the 14,490 found in 2003, but significantly lower than the 27,811 found in 1999, by 54%. The magnitude and rate of the decline are of major conservation concern. Great Skua Stercorarius skua predation is thought the most likely cause but other factors such as poor food supply cannot be ruled out. The importance of continued monitoring of Leach’s Storm-petrel and Great Skua is discussed.
Treatment outcomes of Pumani bubble-CPAP versus oxygen therapy among preterm babies presenting with respiratory distress at a tertiary hospital in Tanzania—Randomised trial

Background Respiratory distress syndrome (RDS) is the most common respiratory disease in premature babies and the major cause of morbidity and mortality among preterm babies. Effective treatment of these babies requires exogenous surfactant and/or mechanical ventilation but these are of limited availability in low and middle income countries. A cheaper, simpler and more accessible treatment for preterms with RDS called bubble-continuous positive airway pressure (bCPAP) has been reported to be effective in treating RDS in preterm babies with varying levels of effectiveness ranging from 42% to 85%. We aimed to implement and determine the efficacy of bCPAP and its immediate outcomes as compared to oxygen therapy in preterm babies presenting with respiratory distress at a tertiary hospital in Tanzania. Method A randomized control trial, conducted from December 2016 to May 2017, included all preterm babies admitted at the neonatal care unit presenting with signs of respiratory distress and meeting the inclusion criteria. The primary outcome was survival while the secondary outcomes were treatment duration, duration of hospital stay and treatment complications. Results A total of 824 babies were admitted in the neonatal care unit during the study period. Of these, 187 babies were preterm and 48 babies were recruited and randomized (25 bCPAP vs 23 oxygen). The overall survival to discharge for all eligible participants (n = 48) was 58.2% compared to those who adhered to treatment protocol (n = 45, 62.2%). Babies in the bCPAP group had higher survival (17/22; 77.3%) as compared to their counterparts in the oxygen therapy group (11/23; 47.8%). Babies treated with bCPAP had 52% lower risk of death (crude HR 0.48, 95% CI = 0.16–1.43) compared to babies receiving oxygen therapy. The median duration of treatment for babies in the oxygen therapy group was 2 (Range 0–16) days compared to 2 (Range 0–5) days in the bCPAP group. The median duration of hospital stay for babies receiving bCPAP was 14 (range 7–43) days. Nasal bleeding was commonly observed among babies in the bCPAP group as compared to those in the oxygen therapy group. Conclusion This study revealed that treatment with bCPAP had a 30% clinical improvement in survival to discharge. Our findings highlight the role of bCPAP in reducing neonatal mortality in resource limited settings but further adequately powered studies in this or similar settings are required.
Short-term effect of osteopathic manual techniques (OMT) on respiratory function in healthy individuals

Background Respiratory system diseases are some of the most common pathologies worldwide. Although osteopathic manual therapy (OMT) is used predominantly to treat other pathologies, certain OMT techniques have been shown to improve patients’ respiratory function. Objectives The aim of this study was to assess the influence of osteopathic techniques on breathing. Methods Tests were performed with the use of a spirometer and the results were expressed as Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), and Peak Expiratory Flow (PEF). Thirty healthy males and females between the age of 18 and 50 took part in the research. Fifteen individuals were randomly assigned to the experimental group and fifteen persons were assigned to the placebo group. The participants from the experimental group were treated with such osteopathic techniques aimed at the pulmonary system as the thoracic thrust (manipulations of vertebral joints and ribs), the sternal pump technique and stretching of the diaphragm. The placebo group was treated with soft tissue therapy (STT) techniques for the masseter muscle. Results The described set of osteopathic techniques exerts an influence on PEF in healthy individuals; however, it does not affect FVC and FEV1. Conclusion Osteopathic techniques do not seem to improve lung health, as reflected in FEV1 and FVC, but they improve the respiratory function aspects reflected by PEF in the participants without any history of lung disease.
Phylogeography of Organophosphate Resistant ace Alleles in Spanish Olive Fruit Fly Populations: A Mediterranean Perspective in the Global Change Context

The olive fruit fly (olf) Bactrocera oleae is the most damaging olive pest. The intensive use of organophosphates (OPs) to control it, led to an increase in resistance in field populations. This study assesses the presence and distribution of three mutations at the ace gene related to target site insensitivity to OPs in Spain. Samples from other Mediterranean countries were included as external references. Resistance-conferring alleles (from exons IV and VII of the ace gene) reached almost an 80% frequency in olf Spanish populations. In total, 62% of them were homozygous (RR/RR), this being more common in eastern mainland Spain. High frequencies of RR/RR individuals were also found in North Mediterranean samples. Conversely, in Tunisia, only sensitive alleles were detected. Finally, the exon X mutation ∆Q3 had an extremely low frequency in all samples. The high frequency of genotype RR/RR in Spain indicates high fitness in an agroecosystem treated with pesticides, in contrast to ∆Q3. At exon IV all flies carried the same haplotype for the allele conferring resistance. The sequence analysis at this exon suggests a unique origin and fast expansion of the resistant allele. These results provide evidence that OPs appropriate use is needed and prompt the search for alternative methods for olf pest control.
Utility of geometric morphometrics for inferring feeding habit from mouthpart morphology in insects: tests with larval Carabidae (Insecta: Coleoptera)

Feeding habits are important life-history traits in animals; however, methods for their determination are not well established in many species. The larvae of the beetle family Carabidae are an example. The present study tested the utility of geometric morphometrics of mouthpart morphology to infer the feeding habits of carabid larvae. Using Pterostichus thunbergi as a model system, larval feeding habits were inferred using geometric morphometrics of mouthparts and the results were compared with those obtained from rearing experiments. The rearing experiments indicated that P. thunbergi larvae are carnivores that require snails as an essential part of the diet. Through geometric morphometrics, associations between mouthpart morphology and larval feeding habits were confirmed for species in which these two traits are known. A discriminant analysis using these associations classified P. thunbergi larvae as snail/slug feeders, which is a result compatible with the rearing experiments. Geometric morphometrics also revealed that morphological integration and ontogenetic shape change might play roles in the diversification of mouthpart morphology. Overall, these results demonstrate the utility of the geometric morphometrics of mouthparts to infer feeding habit and to clarify the mechanisms of mouthpart morphological diversification in the study group, and the results also serve as a basis for future studies of other insect groups.
Notch-Inflammation Networks in Regulation of Breast Cancer Progression

Members of the Notch family and chronic inflammation were each separately demonstrated to have prominent malignancy-supporting roles in breast cancer. Recent investigations indicate that bi-directional interactions that exist between these two pathways promote the malignancy phenotype of breast tumor cells and of their tumor microenvironment. In this review article, we demonstrate the importance of Notch-inflammation interplays in malignancy by describing three key networks that act in breast cancer and their impacts on functions that contribute to disease progression: (1) Cross-talks of the Notch pathway with myeloid cells that are important players in cancer-related inflammation, focusing mainly on macrophages; (2) Cross-talks of the Notch pathway with pro-inflammatory factors, exemplified mainly by Notch interactions with interleukin 6 and its downstream pathways (STAT3); (3) Cross-talks of the Notch pathway with typical inflammatory transcription factors, primarily NF-κB. These three networks enhance tumor-promoting functions in different breast tumor subtypes and act in reciprocal manners, whereby Notch family members activate inflammatory elements and vice versa. These characteristics illustrate the fundamental roles played by Notch-inflammation interactions in elevating breast cancer progression and propose that joint targeting of both pathways together may provide more effective and less toxic treatment approaches in this disease.
NUTRITIONAL QUALITY OF BASMATI RICE GENOTYPES

Eleven aromatic and one non-aromatic fine grain genotypes of rice (OlJlZ8 sativa L.) were analysed for proximate principles, energy, macro and micro minerals, carbohydrate components, thiamine and ribofloavin. Variations in proximate principles, energy, macro and micro minerals were found in rice genotypes evaluated. Carbohydrates partitioning revealed that starch, amylose and amylopectin in PR·I06 differed significantly from other basmati genotypes whereas non significant differences were observed for reducing sugars, sucrose, fructose and glucose among genotypes. Thiamine and riboflavin ranged from 0.063 to 0.073 and 0.029 to 0.037 mg/lOO g.