Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic diversity, structure, and demography of Pandanus boninensis (Pandanaceae) with sea drifted seeds, endemic to the Ogasawara Islands of Japan: Comparison between young and old islands

Pandanus boninensis, endemic to the Ogasawara Islands, Japan, is distributed on both the older Bonin and younger Volcano Islands. In this study, we conducted population genetic analyses of P. boninensis on these islands to examine the population diversity and structure across old and young islands, to assess potential differences in population demography with island age, and to collect any evidence of migration between old and young islands. We found that the genetic diversity of expressed sequence tag (EST)–based microsatellite (SSR) markers, the nucleotide diversity of nuclear DNA sequences, and the haplotype diversity of chloroplast DNA on young islands were lower than those on old islands. Clustering analyses of EST‐SSR indicated that populations on old islands were strongly diverged from those on young islands. Approximate Bayesian computation analysis of EST‐SSR suggested that population expansion occurred on old islands while population reduction occurred on young islands. We also found evidence of migration among old islands (mostly from south to north), while it appears that there have been very few migration events between old and young islands. These differences could be due to the fact that young islands tend to be geographically isolated and support smaller populations that began a shorter time ago from limited founders. The P. boninensis populations on the Volcano Islands are interesting from an evolutionary perspective as they constitute a classic example of the early stages of progressive colonization on oceanic islands with small effective population sizes and low genetic diversity.
Kdm6a Deficiency Activates Inflammatory Pathways, Promotes M2 Macrophage Polarization, and Causes Bladder Cancer in Cooperation with p53 Dysfunction

Purpose: Epigenetic deregulation is deeply implicated in the pathogenesis of bladder cancer. KDM6A (Lysine (K)-specific demethylase 6A) is a histone modifier frequently mutated in bladder cancer. However, the molecular mechanisms of how KDM6A deficiency contributes to bladder cancer development remains largely unknown. We hypothesized that clarification of the pathogenic mechanisms underlying KDM6A-mutated bladder cancer can help in designing new anticancer therapies. Experimental Design: We generated mice lacking Kdm6a in the urothelium and crossed them with mice heterozygous for p53, whose mutation/deletion significantly overlaps with the KDM6A mutation in muscle-invasive bladder cancer (MIBC). In addition, BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine), a cigarette smoke-like mutagen, was used as a tumor-promoting agent. Isolated urothelia were subjected to phenotypic, pathologic, molecular, and cellular analyses. The clinical relevance of our findings was further analyzed using genomic and clinical data of patients with MIBC. Results: We found that Kdm6a deficiency activated cytokine and chemokine pathways, promoted M2 macrophage polarization, increased cancer stem cells and caused bladder cancer in cooperation with p53 haploinsufficiency. We also found that BBN treatment significantly enhanced the expression of proinflammatory molecules and accelerated disease development. Human bladder cancer samples with decreased KDM6A expression also showed activated proinflammatory pathways. Notably, dual inhibition of IL6 and chemokine (C-C motif) ligand 2, upregulated in response to Kdm6a deficiency, efficiently suppressed Kdm6a-deficient bladder cancer cell growth. Conclusions: Our findings provide insights into multistep carcinogenic processes of bladder cancer and suggest molecular targeted therapeutic approaches for patients with bladder cancer with KDM6A dysfunction.
Micro-computed tomographic assessment of the variability and morphological features of root canal system and their ramifications

Abstract Objectives This study assessed the incidence and variability features of root canals system (RCS) and their ramifications according to Pucci & Reig (PR) (1944) and the American Association of Endodontists (AAE) (2017) by micro-computed tomography (μCT). Methodology 500 representative extracted human teeth of each tooth group (n=50) (maxillary/mandibular central and lateral incisors, canines, first and second premolars and molars) were scanned by μCT with a resolution of 26.70 μm. The reconstructed cross-sections images and the visualization of the continuous slices in the transversal axis were performed using DataViewer software. RCS were classified according to Pucci & Reig (main canal, collateral canal, lateral canal, secondary canal, accessory canal, intercanal, recurrent canal) and AAE (main canal, accessory canal, lateral canal). The apical deltas were assessed for both classifications. The prevalence of apical deltas was evaluated using the Chi-squared test (p<0.05). Results According to PR, a higher incidence of lateral canals was observed in maxillary canines (10%), central incisors (8%) and first premolars (6%). Using AAE, the highest incidence of lateral canals was observed in the mandibular first premolars (85%), first and second molars (84%), lateral incisors (67%), canines (59%), and in maxillary first premolars (52%). Regarding accessory canals, the PR showed a frequency in 2% of the maxillary lateral incisors and maxillary and mandibular first premolars and 3% of mandibular first and second molars. On the other hand, the AAE showed the highest incidence of accessory canals in 86% of the maxillary first premolars, 71% in mandibular lateral incisors, 69% in mandibular first premolars, 65% in mandibular canines, and 56% in maxillary canines. The PR showed the lowest incidence of apical deltas for all dental groups when compared with AAE (p=0.004). Interestingly, distal canals in maxillary molars showed a significant discrepancy between classifications (p=0.027). Conclusions μCT enabled accurately describing the RC system and related ramifications, adding to the PR and AAE classifications, with some discrepancies reported for maxillary molars. Clinical Relevance This μCT study enabled a thorough description of the variability among root canals and their ramifications, including clinically relevant details on the presence and location of lateral canals and accessories in all human tooth groups, beyond the currently existing classification systems.
Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile

The present work was aimed for the preparation of a stable nanostructured lipid carrier (NLC) system for the delivery of N-palmitoylethanolamide (PEA) to the back of the eye. PEA is an interesting natural compound showing anti-inflammatory and neuroprotective activities. The limits of PEA (poor solubility and high instability) justify its nanoencapsulation into drug delivery systems. Two different well-known techniques were compared to formulate NLC: the high shear homogenization technique (HSH) and the method based on a combination of HSH technique and ultrasonication (HSH/US). Nanoparticles were evaluated in relation to mean size, homogeneity, surface charge, and physical stability by Turbiscan technology. Retinal distribution of PEA was carried out in a rat eye after single instillation of PEA-NLC ophthalmic formulation. The novel formulation delivered remarkable levels of PEA to the retina. Lastly, topical administration of PEA-NLC ophthalmic formulation was able to significantly inhibits retinal tumor necrosis factor-α (TNF-α) levels in streptozotocin-induced diabetic rats. The present findings suggest that the novel ophthalmic formulation may be useful for the treatment of retinal diseases such as diabetic retinopathy. Clinical studies are in progress to evaluate this possibility.
Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle

Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.
Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which post-translationally modify proteins through poly(ADP-ribosyl)ation (PARylation)—the transfer of ADP-ribose chains onto amino acid residues—with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells—cancerous and non-cancerous—are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment.
Association between Social Support and Frailty among Older People with Depressive Disorders

ABSTRACT Objectives This study aimed at examining the association between social support and frailty status, specifically amongst older people with depressive disorders. Methods It was conducted in older people, aged 65 and over, with depressive disorders at the Psychiatry Outpatient Unit of Songklanagarind Hospital, Thailand. The main independent variable, level of social support, was assessed using the Inventory of Social Support Behaviors (ISSB) – Thai. The main dependent variable, frailty status, was assessed via the adapted Fried Frailty Phenotype. Bivariate and ordinal regression analyses were conducted to examine the relationships between variables. Results In our study sample, 32% of the 147 participants were considered frail, 51% pre-frail, and 17% robust. From the ordinal regression analysis, four variables – social support score, current depressive symptoms, level of education, and key family caregivers – were statistically significantly associated with frailty status. The odds of having pre-frailty and frailty were statistically significantly reduced by a factor of 0.99, or around 1.0 percent, for each 1-point increment of the social support scale (Ordinal OR 0.99, 95% CI = 0.97–0.99, p-value = 0.015). Conclusions Social support interventions should be designed to influence multiple items of the social support scale at the same time, which might, therefore, have a substantial effect on frailty status among the older population. Clinical implications We recommend a regular practice that focuses not only on biological (i.e., prescribing medications) and psychological aspects (i.e., providing psychotherapy) but also on the social dimension of older people living with frailty and depressive disorders.
Long term dietary supplementation with microalgae increases plasma docosahexaenoic acid in milk and plasma but does not affect plasma 13,14-dihydro-15-keto PGF2α concentration in dairy cows

Abstract The aims of the study were to determine the long-term effects of dietary supplementation with microalgae (SCIM) on milk and blood fatty acid (FA) composition and reproductive hormones in early lactation dairy cows. Sixty Holstein–Friesian dairy cows (30 per treatment) were unsupplemented (Control) or supplemented with 100 g of SCIM (Schizochytrium limacinum sp.) per cow per day from 25 ± 0.5 d post-partum for 98 d. Intake and milk yield were recorded daily, with milk samples collected at weeks 0, 1, 2, 4, 8 and 14, and blood samples collected from 12 representative pairs per treatment at weeks 0, 2, 4, 8, and 14 for subsequent analysis of FA, β-hydroxybutyrate, non-esterified fatty acids and glucose. At 33 ± 0.9 d postpartum the oestrus cycle of 24 cows (12 per treatment) were synchronized and plasma 13,14-dihydro-15-keto PGF2α (PGFM) concentrations determined following an oxytocin challenge. Data were analysed by repeated measures analysis of variance. There was no effect of treatment on dry matter intake, milk yield or milk fat content, with mean values across treatments of 22.1 and 40.6, and 37.2 g/kg respectively. Milk fat concentration of C22:6 n-3 increased rapidly in cows receiving SCIM, reaching a maximum of 0.38 g/100 g FA by week 14. Similarly, blood concentration of C22:6 n-3 increased to 1.6 g/100 g FA by week 14 in cows fed SCIM. There was no effect of treatment on plasma metabolites, but plasma glucose was lower in cows fed SCIM compared to the Control at week 2, and higher in week 8. There was no effect of treatment on peak plasma PGFM concentration or area under the curve. It is concluded that feeding SCIM rapidly increases blood and milk concentrations of C22:6 n-3 which are maintained over time, but does not improve plasma PGFM in dairy cows.
Implication of Anopheles funestus in malaria transmission in the city of Yaoundé, Cameroon

The contribution of Anopheles funestus to malaria transmission in the urban environment is still not well documented. The present study assesses the implication of An. funestus in malaria transmission in two districts, Nsam and Mendong, in the city of Yaoundé. Adult mosquitoes were collected using Centers for Disease Control and Prevention miniature light traps (CDC-LT) and human landing catches from April 2017 to March 2018 and were identified morphologically to the species level. Those belonging to the Anopheles gambiae complex and to the Anopheles funestus group were further processed by PCR to identify members of each complex/group. Anopheline mosquitoes were analysed to determine their infection status using an enzyme-linked immunosorbent assay. Bioassays were conducted with 2–5-day-old female Anopheles funestus and An. gambiae s.l. to determine their susceptibility to permethrin, deltamethrin and dichlorodiphenyltrichloroethane (DDT). Six anopheline species were collected in the peri-urban district of Mendong: Anopheles gambiae, An. coluzzii, An. funestus, An. leesoni, An. ziemanni and An. marshallii; only four out of the six were recorded in Nsam. Of the two members of the Anopheles gambiae complex collected, An. coluzzii was the most prevalent. Anopheles coluzzii was the most abundant species in Nsam, while An. funestus was the most abundant in Mendong. Both Anopheles funestus and An. gambiae s.l. were found to be infected with human Plasmodium at both sites, and both were found to be resistant to DDT, permethrin, and deltamethrin. This study confirms the participation of An. funestus in malaria transmission in Yaoundé and highlights the need to also target this species for sustainable control of malaria transmission.
UK military women: mental health, military service and occupational adjustment.

BACKGROUND Recently, the UK Armed Forces have revised the ground close combat role to include women. AIMS To assess the potential mental health impact of this initiative we examined gender differences in deployment patterns, work strain, occupational factors, mental health, alcohol use and help-seeking following operational deployment. METHODS The study was a secondary analysis of self-report survey data; 8799 men (88%) and 1185 women (12%) provided data. A sub-sample (47%, n = 4659) provided data concerning post-deployment help-seeking. The latter consisted of 408 women (8.8%) and 4251 men (91%). RESULTS With the exception of alcohol misuse, which was significantly lower for women, women reported significantly more common mental disorder symptoms, subjective depression and self-harm. Women were significantly more likely to seek help from healthcare providers. Men were significantly more likely to have deployed operationally and for longer cumulative periods. Subjective work strain, but not job control, was significantly lower for women whose military careers were significantly shorter. Post-traumatic stress disorder (PTSD) symptom intensity was similar to men. CONCLUSIONS With the exception of PTSD and alcohol misuse, UK military women experience more mental health-related problems than military men. This finding was not related to the more arduous aspects of military service as women served for shorter times, deployed less and for shorter cumulative periods and were less likely to report work-related stress.
Leptin-mediated differential regulation of microsomal triglyceride transfer protein in the intestine and liver affects plasma lipids

The hormone leptin regulates fat storage and metabolism by signaling through the brain and peripheral tissues. Lipids delivered to peripheral tissues originate mostly from the intestine and liver via synthesis and secretion of apolipoprotein B (apoB)-containing lipoproteins. An intracellular chaperone, microsomal triglyceride transfer protein (MTP), is required for the biosynthesis of these lipoproteins, and its regulation determines fat mobilization to different tissues. Using cell culture and animal models, here we sought to identify the effects of leptin on MTP expression in the intestine and liver. Leptin decreased MTP expression in differentiated intestinal Caco-2 cells, but increased expression in hepatic Huh7 cells. Similarly, acute and chronic leptin treatment of chow diet-fed WT mice decreased MTP expression in the intestine, increased it in the liver, and lowered plasma triglyceride levels. These leptin effects required the presence of leptin receptors (LEPRs). Further experiments also suggested that leptin interacted with long-form LEPR (ObRb), highly expressed in the intestine, to down-regulate MTP. In contrast, in the liver, leptin interacted with short-form LEPR (ObRa) to increase MTP expression. Mechanistic experiments disclosed that leptin activates signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling pathways in intestinal and hepatic cells, respectively, and thereby regulates divergent MTP expression. Our results also indicated that leptin-mediated MTP regulation in the intestine affects plasma lipid levels. In summary, our findings suggest that leptin regulates MTP expression differentially by engaging with different LEPR types and activating distinct signaling pathways in intestinal and hepatic cells.
Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.
Lessons for the courtroom from the study of Flashbulb memory: an integrative review

ABSTRACT In legal proceedings, when no corroboration is possible with external sources of evidence, judges and jurors derive from their own experience the criteria to ascertain if a memory report is accurate and a witness credible. These legal criteria closely resemble the aspects traditionally investigated by literature on Flashbulb memory (i.e., consistency, confidence, quantity), but have failed to obtain a generalised consensus within the scientific community. Drawing up a set of univocal rules upon which to base a conclusion regarding witnesses’ credibility is a difficult task, from both legal and scientific points of view. Respectful cooperation between cognitive science and criminal law will encompass both technical support by expert witnesses, and updating guidelines for fact-finders. This cooperation would prevent the risk of common sense fallacies in the legal process, preserving the legal autonomy to evaluate witness credibility.