Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic data reveal a protracted window of introgression during the diversification of a neotropical woodcreeper radiation *

The incidence of introgression during the diversification process and the timespan following divergence when introgression is possible are poorly understood in the neotropics where high species richness could provide extensive opportunities for genetic exchange. We used thousands of genome‐wide SNPs to infer phylogenetic relationships, calculate ages of splitting, and to estimate the timing of introgression in a widespread avian neotropical genus of woodcreepers. Five distinct introgression events were reconstructed involving taxa classified both as subspecies and species including lineages descending from the basal–most split, dated to 7.3 million years ago. Introgression occurred between just a few hundred thousand to about 2.5 million years following divergence, suggesting substantial portions of the genome are capable of introgressing across taxa boundaries during a protracted time window of a few million years following divergence. Despite this protracted time window, we found that the proportion of the genome introgressing (6–11%) declines with the time of introgression following divergence, suggesting that the genome becomes progressively more immune to introgression as reproductive isolation increases.
Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated.
Comparison of GTR, T-PRF and open-flap debridement in the treatment of intrabony defects with endo-perio lesions: a randomized controlled trial

Background Titanium- prepared platelet rich fibrin (T-PRF) is an autologous hemo-component with a high concentration of platelets that also incorporates leukocytes, and growth factors into the dense fibrin matrix and can be used as a healing biomaterial. This study assesses the adjunctive use of T-PRF in intrabony defects (IBDs) with open flap debridement (OFD) in comparison with guided tissue regeneration (GTR) as a gold standard and OFD alone as a control. Material and Methods A total of 45 patients (15 per group) were randomized as either T-PRF (test group), GTR (test group), or OFD alone (control group) sites. Probing depth (PD), clinical attachment level (CAL), and IBD were recorded. The radiographic depth of IBD was also measured. Primary outcomes assessed were changes in PD, CAL, and radiographic IBD that were assessed at the beginning and nine months later. Results The PRF and GTR group showed significant improvement in clinical parameters compared with the OFD alone (control group) at nine months. While there were no significant differences in PD and CAL between test groups (T-PRF and GTR groups), the significant difference was found in radiographic IBD depth. Conclusions T-PRF may give similar successful results as GTR in the treatment of IBDs with endo-perio lesions. Key words:Flap surgery, guided tissue regeneration, intrabony defects, periodontitis, root canal therapy.
Single Nucleotide Polymorphism rs6942067 Is a Risk Factor in Young and in Non-Smoking Patients with HPV Negative Head and Neck Squamous Cell Carcinoma

Genetic factors behind the increasing incidence of human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) in young non-smokers are suspected, but have not been identified. Recently, rs6942067, a single nucleotide polymorphism (SNP) located upstream of the DCBLD1 gene, was found associated with non-smoking lung adenocarcinoma. To validate if this SNP is also implicated in HNSCC, participants of The Cancer Genome Atlas HNSCC cohort were investigated for rs6942067 status, associated DCBLD1 expression, and clinical characteristics. Occurrence of the rs6942067 GG genotype is significantly higher in young and in HPV negative non-smoking HNSCC than in other HNSCC. Additionally, rs6942067 GG is associated with higher DCBLD1 expression in HNSCC and patients with high DCBLD1 expression have a worse overall survival at three years, both in univariate and multivariate analysis. Furthermore, high DCBLD1 expression is associated with activation of the integrin signaling pathway and its phosphorylation with EGFR and MET. Collectively, these findings suggest that DCBLD1 plays a critical role in HNSCC and demonstrate an association between rs6942067 and clinical characteristics of young age and HPV negative non-smoking status in HNSCC patients.
Ca2+ Channels Mediate Bidirectional Signaling between Sarcolemma and Sarcoplasmic Reticulum in Muscle Cells

The skeletal muscle and myocardial cells present highly specialized structures; for example, the close interaction between the sarcoplasmic reticulum (SR) and mitochondria—responsible for excitation-metabolism coupling—and the junction that connects the SR with T-tubules, critical for excitation-contraction (EC) coupling. The mechanisms that underlie EC coupling in these two cell types, however, are fundamentally distinct. They involve the differential expression of Ca2+ channel subtypes: CaV1.1 and RyR1 (skeletal), vs. CaV1.2 and RyR2 (cardiac). The CaV channels transform action potentials into elevations of cytosolic Ca2+, by activating RyRs and thus promoting SR Ca2+ release. The high levels of Ca2+, in turn, stimulate not only the contractile machinery but also the generation of mitochondrial reactive oxygen species (ROS). This forward signaling is reciprocally regulated by the following feedback mechanisms: Ca2+-dependent inactivation (of Ca2+ channels), the recruitment of Na+/Ca2+ exchanger activity, and oxidative changes in ion channels and transporters. Here, we summarize both well-established concepts and recent advances that have contributed to a better understanding of the molecular mechanisms involved in this bidirectional signaling.
Long‐lasting microbial dysbiosis and altered enteric neurotransmitters in adult rats following adolescent binge ethanol exposure

Human alcoholism and ethanol exposure of adult mice cause acute microbial dysbiosis. Adolescent binge drinking is common, but the effect of adolescent ethanol exposure on the adult microbiome and enteric neurotransmitters has not been studied. In the current study, male Wistar rats received adolescent intermittent ethanol (AIE) treatment, and fecal samples were collected on postnatal day (P)54 and P95 for bacterial 16S rRNA amplicon sequencing. Cecal tissue was collected on P95 for analysis of innate immune and neurotransmitter marker expression. At the genus level, AIE treatment altered the relative abundance of several microbes, including decreased relative abundance of Dehalobacterium and CF231 (a member of the Paraprevotellaceae family) that persisted into adulthood. Across aging, the relative abundance of several microbes was altered in both control‐ and AIE‐treated rats. At P95, AIE exposure was associated with increased cecal serotonin levels and reduced choline acetyltransferase gene expression. Taxonomic shifts at P54 and at P95 suggest that AIE causes both immediate and lasting microbial dysbiosis. The lasting microbial dysbiosis was accompanied by alterations of enteric neurotransmitters.
Family Impacts of Severe Dental Caries among Children in the United Kingdom

The aim of this study was to evaluate the family impacts of severe dental caries among children. Data from 3859 school-age children (5-, 8-, 12- and 15-year-olds) who participated in the 2013 Children’s Dental Health Survey, a national cross-sectional survey in England, Wales and Northern Ireland, were used. Severe dental caries was defined as having at least one tooth with pulpal involvement, ulceration, fistula, or abscess (PUFA). Family impacts were measured using seven items of the Family Impact Scale (FIS). The association between severe dental caries and family impacts was assessed in logistic regression models, adjusting for child’s age, gender, and country of residence; parent’s marital status, education, and job classification; and area deprivation. Severe dental caries among children showed a significant negative impact on family life (Odds Ratio: 6.00; 95% Confidence Interval: 3.34–10.78). Parents of children with severe dental caries had greater odds of taking time off work (OR: 2.75; 95% CI: 1.16–6.54), reporting the child needed more attention (OR: 4.08; 95% CI: 2.15–7.75), feeling guilty (OR: 6.32; 95% CI: 3.26–12.26), feeling stressed (OR: 7.34; 95% CI: 4.15–12.99), having normal activities disrupted (OR: 5.78; 95% CI: 2.71–12.34), and having sleep disrupted (OR: 4.94; 95% CI: 2.78–8.76). Having severe dental caries was not associated with financial difficulties in the family (OR: 1.64; 95% CI: 0.49–5.51). The observed association between severe dental caries and family impacts was independent of child and family sociodemographic characteristics. The findings underscore the importance of preventive interventions to avoid severe dental caries in children and subsequently reduce negative impacts on their family life.
Down-Grading of Ipsilateral Hydronephrosis by Neoadjuvant Chemotherapy Correlates with Favorable Oncological Outcomes in Patients Undergoing Radical Nephroureterectomy for Ureteral Carcinoma

Few studies have analyzed the details of neoadjuvant chemotherapy (NAC)-induced changes in patients with upper tract urothelial carcinoma. This study aimed to describe the impact of down-grading ipsilateral hydronephrosis by NAC for ureteral carcinoma. An observational study was conducted in 32 patients with cT1-3N0M0 ureteral carcinoma treated with NAC and radical nephroureterectomy. Hydronephrosis was classified into five grades based on computed tomography findings. We focused on the differences between the baseline and post-NAC status of ipsilateral hydronephrosis, radiographic tumor response, and blood markers. Down-grading, no change, and up-grading was observed in 10 (31%), 21 (66%), and 1 (3%) patients, respectively. In univariate analysis, locally advanced disease (cT3), severe hydronephrosis (grade 3/4) at baseline, no change/up-grading of hydronephrosis after NAC, and pathological lymphovascular involvement were identified as potential prognostic factors of progression-free and cancer-specific survival after radical nephroureterectomy. Locally advanced disease (cT3) at baseline and no change/up-grading of hydronephrosis by NAC were independently associated with poor progression-free survival. Notably, none of the patients with NAC-induced down-grading of hydronephrosis died of ureteral carcinoma during the follow-up. We reported the prognostic impact of down-grading of ipsilateral hydronephrosis, which could serve as a useful aid or clinical marker for decision-making.
The Effect of Chromium Nanoparticles and Chromium Picolinate in the Diet of Chickens on Levels of Selected Hormones and Tissue Antioxidant Status

Simple Summary We have postulated that supplementation with Cr can increase serotonin levels and improve the antioxidant status of chickens, with no adverse effect on the secretion of other hormones. Obtaining such results may be beneficial in high-density rearing of poultry exposed to many stressors. The studies compared the effects of two forms of Cr (Cr-Pic and Cr-NP) found at two doses 3 and 6 mg/kg. It was found that at the dose of 3 mg/kg, the expected beneficial results can be obtained (increase in serotonin and decrease in norepinephrine level), however, due to the deterioration of the antioxidative system, these studies should be continued to verify these results. Due to the adverse effect of Cr at 3 mg/kg on the antioxidant status of chickens, this level of Cr should not be considered in both forms Cr-Pic and Cr-NP as a feed additive for broiler chickens. In the future, studies on the potential beneficial effects of Cr on the organism should take into account doses lower than 3 mg/kg. Abstract We have postulated that supplementation with Cr can increase serotonin levels and improve the antioxidant status of chickens, with no adverse effect on the secretion of other hormones. The study aimed to determine what form and dose of Cr more favorably affect the level of selected hormones (insulin, glucagon, serotonin, dopamine, noradrenaline, histamine, T3 and T4) and the antioxidant status (level of malondialdehyde and lipid peroxides, activity of superoxide dismutase and catalase) of chicken tissues. The experiment was carried out on chickens randomly divided into five treatment groups. The basal diets (control group) were supplemented with two levels of Cr (3 and 6 mg/kg) and two Cr sources: Cr-picolinate (Cr-Pic) and Cr-nano (Cr-NP) to obtain four experimental diets: 3 mg/kg Cr-Pic, 6.0 mg/kg Cr-Pic, 3.0 mg/kg Cr-NP. and 6.0 mg/kg Cr-NP. The addition of Cr in both forms increased the level of serotonin at a dose of 3 mg/kg and, at the same time, reduced the level of noradrenaline. The addition of Cr at 3 mg/kg, irrespective of the form used, regulated the level of hormones of carbohydrate metabolism (increasing insulin levels and reducing glucagon levels) and had an adverse effect on the antioxidant status of the liver and breast muscle. Due to the adverse effect of Cr at 3 mg/kg on the antioxidant status of chickens, this level of Cr should not be considered in both forms Cr-Pic and Cr-NP as a feed additive for broiler chickens. In the future, studies on the potential beneficial effects of Cr on the organism should take into account doses lower than 3 mg/kg.
Chemical-Sensory Traits of Fresh Cheese Made by Enzymatic Coagulation of Donkey Milk

Making cheese from donkey milk is considered unfeasible, due to difficulties in coagulation and curd forming. Two recent studies have reported the protocols for making fresh cheese by using camel chymosin or calf rennet, but the chemical and sensory characteristics of the products were not thoroughly investigated. The present paper aims to give a further contribution to the field, by investigating cheesemaking with microbial rennet and evaluating the chemical composition, total fatty acid, volatile organic compounds (VOCs) and sensory profile of the resultant product. Six trials were undertaken at laboratory scale on donkey milk from a Martina Franca ass, by applying the technological scheme as reported for calf rennet, with some modifications. Bulk cow milk was used as a control. Donkey milk coagulated rapidly, but the curd remained soft, and was only suitable for making fresh cheese; differently, cow milk coagulated almost instantaneously under these strong technological conditions, giving rise to a semi-hard curd in very short time. The moisture level of donkey cheese was almost the same as reported in the literature, whereas the yield was higher, probably due to the high protein content of the milk used. The total fatty acid composition of cheese presented some differences with respect to milk, mostly consisting in a higher presence of saturated compounds. A connection with a better retention of the large sized fat globules into the curd was hypothesised and discussed. The VOC analyses, performed by solid-phase micro extraction gas chromatography-mass spectrometry, allowed the identification of 11 compounds in milk and 18 in cheese. The sensory characteristics of donkey cheese were strongly different with respect to the control, and revealed unique and pleasant flavours.
miR‐181a/b‐5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA

Type 2 diabetes mellitus (T2DM) is a growing burden in low‐and middle‐income countries. Changing lifestyles and lack of physical activity are some of the reasons contributing to this epidemic increase. Co‐morbidities associated with T2DM are largely due to the complications which arise as a consequence of endothelial dysfunction. Platelet derived growth factor‐alpha (PDGFRA) is a protein responsible for cell proliferation, angiogenesis, migration and invasion. Increased levels of PDGFRA have been reported in T2DM. This study assessed the epigenetic regulation of PDGFRA through microRNAs (miR‐181a/b‐5p). Using a bioinformatics‐based approach, we assessed the binding of miR‐181a/b‐5p to PDGFRA. Experimentally, this binding was confirmed using a dual luciferase reporter assay. Further, we overexpressed miR‐181a/b‐5p in Human umbilical vein endothelial cells (HUVECs) and the influence of over‐expression on cell proliferation, migration and angiogenesis was assessed using in‐vitro approaches. The influence of miR‐181a/b‐5p over expression on cellular apoptosis was ascertained using a TUNEL assay with concomitant changes being observed in the levels of Bcl‐2 and cleaved Caspase‐3.In HUVECs, PDGFRA is a direct target for miR‐181a/b‐5p. Over expression of miR‐181a/b‐5p decreased cellular proliferation, migration, invasion, and tube formation—a surrogate marker for angiogenesis. miR‐181a/b‐5p may be used as a therapeutic intervention to restrict uncontrolled levels of PDGFRA and thereby rescue the phenotypes of increased cell proliferation, migration, invasion and tube formation. miR‐181a/b negatively regulates PDGFRA levels.
Strangers, Friends, and Lovers Show Different Physiological Synchrony in Different Emotional States

The mere copresence of another person synchronizes physiological signals, but no study has systematically investigated the effects of the type of emotional state and the type of relationship in eliciting dyadic physiological synchrony. In this study, we investigated the synchrony of pairs of strangers, companions, and romantic partners while watching a series of video clips designed to elicit different emotions. Maximal cross-correlation of heart rate variability (HRV) was used to quantify dyadic synchrony. The findings suggest that an existing social relationship might reduce the predisposition to conform one’s autonomic responses to a friend or romantic partner during social situations that do not require direct interaction.
Transcriptional Regulation in Rocket Leaves as Affected by Salinity

Salinity is one of the major abiotic stress causing yield losses and decreasing product quality. The beneficial effects of biostimulant products to enhance plant tolerance to abiotic stresses have been reported in several crops, but their mode of action is poorly understood. This work aims to better understand the effect of salt stress on wild rocket treated with a borage extract. The expression of some of the transcription factors (TFs) typically involved in salt stress response was studied within a 24 h period. Physiological parameters such as chlorophyll, chlorophyll a fluorescence, carotenoids, phenols, and anthocyanin were analyzed. Results obtained showed that salt stress induced a general increase in the expression levels of almost all TFs studied, whereas the treatment with the plant-base extract only induced an increase at specific time points. Moreover, the approach adopted allowed indagating the change in gene expression during time. Different pathways such as sugars metabolism, cuticular wax biosynthesis, and brassinosteroids signaling took part in plant responses.
PI3K activation prevents Aβ42-induced synapse loss and favors insoluble amyloid deposit formation

Excess of Aβ42 peptide is considered a hallmark of the disease. Here we express the human Aβ42 peptide to assay the neuroprotective effects of PI3K in adult Drosophila melanogaster. The neuronal expression of the human peptide elicits progressive toxicity in the adult fly. The pathological traits include reduced axonal transport, synapse loss, defective climbing ability and olfactory perception, as well as lifespan reduction. The Aβ42-dependent synapse decay does not involve transcriptional changes in the core synaptic protein encoding genes bruchpilot, liprin and synaptobrevin. All toxicity features, however, are suppressed by the coexpression of PI3K. Moreover, PI3K activation induces a significant increase of 6E10 and thioflavin-positive amyloid deposits. Mechanistically, we suggest that Aβ42-Ser26 could be a candidate residue for direct or indirect phosphorylation by PI3K. Along with these in vivo experiments, we further analyze Aβ42 toxicity and its suppression by PI3K activation in in vitro assays with SH-SY5Y human neuroblastoma cell cultures, where Aβ42 aggregation into large insoluble deposits is reproduced. Finally, we show that the Aβ42 toxicity syndrome includes the transcriptional shut down of PI3K expression. Taken together, these results uncover a potential novel pharmacological strategy against this disease through the restoration of PI3K activity.
Changes in Antioxidant Activity, Profile, and Content of Polyphenols and Tocopherols in Common Hazel Seed (Corylus avellana L.) Depending on Variety and Harvest Date

The aim of the study was to evaluate the influence of variety and the date of harvest of hazelnut seeds on their antioxidant potential and the profile and content of polyphenols and tocopherols. The research material included the hazelnut seeds of six varieties, harvested from July to September at equal 30-day intervals. Hazelnuts were analyzed for total fat content and antioxidant properties, whereby UPLC-PDA-ESI-MS analysis was used to determine the profile and content of polyphenols, and the HPLC method to determine the content of tocopherols. It was found that the content of fat and tocopherols in nuts increased with the ripening of the nuts. The highest fat content was found in walnut seeds of the Kataloński variety (September) and tocopherols in walnut seeds of the Olbrzym z Halle variety (177.67 mg/kg d.m.). In turn, antioxidant properties and total polyphenols content decreased with the later harvest date. The strongest antioxidant potential was found in the case of Cosford nuts harvested in July (66.93 mmol TE/100 g d.m.). These nuts were also characterized by the highest total polyphenol content (1704.9 mg/100 g d.m.). UPLC-MS analysis allowed the identification of 15 polyphenolic compounds such as phenolic acids, catechins and ellagic acid hexoside in nut seeds.
Noninvasive follicular neoplasm with papillary like nuclear features: A comprehensive analysis with a diagnostic algorithm

Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) lacks the carcinoma label, avoiding aggressive therapy, physiological, social and financial impact of cancer diagnosis. Unfortunately, the preoperative diagnosis is still a challenge. Varied incidence of NIFTP has been document with limited data on preoperative cytological, radiological characteristics and the impact on risk of malignancy in each category of the Bethesda system of reporting thyroid cytopathology.