Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatiotemporal map of key signaling factors during early penis development

The formation of the external genitalia is a highly complex developmental process, considering it involves a wide range of cell types and results in sexually dimorphic outcomes. Development is controlled by several secreted signalling factors produced in complex spatiotemporal patterns, including the hedgehog (HH), bone morphogenic protein (BMP), fibroblast growth factor (FGF) and WNT signalling families. Many of these factors act on or are influenced by the actions of the androgen receptor (AR) that is critical to masculinisation. This complexity of expression makes it difficult to conceptualise patterns of potential importance. Mapping expression during key stages of development is needed to develop a comprehensive model of how different cell types interact in formation of external genitalia, and the global regulatory networks at play. This is particularly true in light of the sensitivity of this process to environmental disruption during key stages of development. The goal of this review is to integrate all recent studies on gene expression in early penis development to create a comprehensive spatiotemporal map. This serves as a resource to aid in visualising potentially significant interactions involved in external genital development.
Approaches towards tissue‐selective pharmacology of the mineralocorticoid receptor

Mineralocorticoid receptor antagonists (MRAs) are highly effective therapies for cardiovascular and renal disease. However, the widespread clinical use of currently available MRAs in cardiorenal medicine is hampered by an increased risk of hyperkalaemia. The mineralocorticoid receptor (MR) is a nuclear receptor responsible for fluid and electrolyte homeostasis in epithelial tissues, whereas pathophysiological MR activation in nonepithelial tissues leads to undesirable pro‐inflammatory and profibrotic effects. Therefore, new strategies that selectively target the deleterious effects of the MR but spare its physiological function are needed. In this review, we discuss recent pharmacological developments starting from novel non‐steroidal MRAs, such as finerenone or esaxerenone, that are now entering clinical use, to concepts arising from the current knowledge of the MR signalling pathway, aiming at receptor–coregulator interaction, epigenetics or downstream effectors of the MR.
Diversifying neighborhoods and schools engender perceptions of foreign cultural threat among White Americans.

A nationally representative survey (N = 2,213) and five experiments (four preregistered, total N = 1,920) revealed that Whites perceived a foreign cultural threat, or a threat to their American culture and way of life, from the projected growth of racial and ethnic minority populations in their majority-White neighborhoods (Studies 1-5) and schools (Study 6). Whites perceived the increasing presence of Arab Americans, Latinos, and Asian Americans to pose an especially strong degree of perceived foreign cultural threat relative to Black Americans, who were perceived as more threatening than no demographic change. Furthermore, perceptions of foreign cultural threat predicted Whites' desires to move out above and beyond other established intergroup threats (e.g., realistic and symbolic threats). These findings highlight how Whites' concerns about losing their American culture and way of life as racial and ethnic minority groups enter majority-White neighborhoods and schools may contribute to the maintenance of racial segregation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Religiosity, Spirituality and Biopsychological Age of Professionals in Russia

The challenges of modern civilization resulted in the premature biological and psychological aging of professionals of working age. This phenomenon raises both medical and psychological problems associated with personality factors that affect psychobiological maturity and the rate of aging. The influence of religiosity and spirituality on biopsychological age remains the least studied area of psychology. Progress in this area will help to identify the components of religiosity—predictors of the aging rate of professionals. The sample included 295 people (148 women) aged 24 to 54 years (average age 31.7 years) and consisted of Christians (67.12%), Muslims (5.76%), Buddhists, deists, Shintoists, etc., (7.79%) and atheists (17.29%). The average work experience was 9 years. Using correlation analysis and methods of multivariate linear regression and t-test for independent samples, we found that the religiosity of professionals increases with natural aging and deterioration of their physical condition and does not depend on gender. Religiosity to a greater extent affects psychological age, the indicator of the psychobiological maturity of a professional and, to a lesser extent, biological age. Most of the indicators of religiosity are inherent in a person who is more mature in psychobiological terms. The biological age of professionals increases due to asthenic experiences, while gaining faith in God, unusual religious experiences and the existential meaning of life can reduce it. An increase in the spirituality of professionals is associated with a slowdown in the rate of biological aging.
Cerebrospinal Fluid Levels of 5-Hydroxyindoleacetic Acid in Parkinson’s Disease and Atypical Parkinsonian Syndromes

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 μg/L, in MSA 13.6 μg/L vs. 24.3 μg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 μg/L, in CBS 18.7 μg/L vs. 24.3 μg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).
Cell-free DNA as a potential biomarker for preeclampsia

Preeclampsia (PE) is defined as hypertension accompanied by hematologic, liver, renal, cerebral, and/or visual disturbances after the 20th week of gestation [1]. PE constitutes a serious pregnancy complication that adversely influences perinatal outcomes. Additionally, PE has been consistently associated with increased incidence of long-term cardiovascular events in both mother and offspring. PE remains an obstetric and public health burden with recent epidemiologic studies showing an increase in its incidence (5–8% of all pregnancies worldwide) due to a higher prevalence of risk factors, such as advanced maternal age, obesity, diabetes, and chronic hypertension [2]. Currently, there is no effective therapy for PE, with the syndrome only remitting after delivery. The difficulty in identifying and testing such therapies is partially explained by the fact that PE is a multifactorial disorder involving pathways related to impaired angiogenesis, inflammation, and oxidative stress, among others that lead to generalized endothelial dysfunction. The etiology of PE seems even more complex when considered the timing of manifestation of the clinical symptoms. Early-onset PE, defined as those diagnosed before 34 weeks of gestation (5–20% of cases), has been associated with inadequate remodeling of the decidual vasculature and placental malperfusion; whereas late-onset PE, defined as those diagnosed after 34 weeks of gestation (~80% of cases), has been associated with maternal morbidities including impaired glucose tolerance, dyslipidemia, obesity, chronic hypertension, and metabolic syndrome. These different pathways seem to converge on the pathophysiology of both types of PE causing placental senescence and stress [3]. Together, these findings justify the ongoing search for useful diagnostic and prognostic biomarkers that may be eventually targeted by novel therapies in PE. Providing new insights into potential biomarkers for PE, exaggerated levels of both maternal and fetal-derived cellfree DNA (cfDNA) fragments have been detected in the blood of PE patients. Moreover, increased circulating cfDNA levels have been associated with disease severity and unfavorable maternal-fetal outcomes in PE [4–9]. While these studies suggest that cfDNA may be useful as a diagnostic and prognostic biomarker for PE, the exact mechanism leading to the release of cfDNA into the maternal circulation and its range of consequences are not fully known. In this commentary, recent studies measuring cfDNA in early-onset, late-onset, or any type of PE are briefly summarized. The overall goal is to point shortcomings of current literature in the field, suggest alternatives to overcome the challenge of assessing circulating cfDNA, and propose required studies to determine the role of cfDNA in mediating the pathogenesis of PE.
Characterization of CwlC, an autolysin, and its role in mother cell lysis of Bacillus thuringiensis subsp. israelensis

Bacillus thuringiensis subsp. israelensis (Bti) has been proven to efficiently control mosquitoes, of which many species are important vectors of human disease. The larvicidal action is attributed to the parasporal crystals formed in the sporulating cells and released upon cell autolysis. In this study, a sporulation‐specific cwlC gene that encodes an N‐acetylmuramoyl‐L‐alanine amidase was characterized in Bti strain Bt‐59. CwlC was the only cell wall hydrolase in Bti found to contain both MurNAc‐LAA and Amidase02_C domains. A recombinant CwlC‐His protein was able to digest the Bacillus cell wall. Deletion of the cwlC gene delayed Bti mother cell lysis without impacting vegetative growth or insecticidal efficacy. Transcriptional analyses indicated that cwlC was expressed at the late sporulation stage and was controlled by SigK. Two other cell wall hydrolase genes, cwlB and cwlE, with high expression levels at T14 in Bt‐59, were also identified. Like cwlC, cwlB expression was controlled by SigK; in contrast, cwlE was found not to be under the control of this sigma factor and unlike the other two, its gene was found to be plasmid encoded.
Supine PCNL-5 year experience in a tertiary care center

Objective: The prone position for percutaneous nephrolithomy (PCNL) has been widely practiced. There has been a shift from prone position to supine position which showed numerous benefits. The aim of our study is to describe the 5 year experience from the perspective of a tertiary care center using a modified Galdakao supine Valdivia position for total tubeless ultra mini supine PCNL, total tubeless supine PCNL, tubeless supine PCNL, and standard supine PCNL. Material and methods: We retrospectively reviewed the data of 90 patients who underwent supine PCNL at the tertiary care center during the period of 5 years from January 2017 to January 2021. The data collection was done from patients’ medical records. Pre operatively, complete examination of the patients with laboratory investigations were done. The modified Clavien classification system was used to classify the perioperative complications of PCNL. Results: Operative time was lowest for ultra mini supine PCNL (50 ± 10.4 min) compared to standard supine PCNL (58 ± 11.2 min). Stones were single in 54 patients and multiple in 40 patients with 4 patients with staghorn stones. The size of the stones in the largest dimension ranged from 1.2 to 5.5 cm.Complete clearance was achieved in 84 (89.7%) patients. Seven patients (7.2%) developed mild fever and four patients (4.5%) required blood transfusion. Conclusion: We found supine PCNL to be an immensely convenient, time-saving practice, and with higher stone free rate compared to prone PCNL. The different techniques of supine PCNL were also useful in patients with horseshoe kidney and calyceal diverticulum which resulted in good outcomes in these patients.
Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study

ABSTRACT Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies. Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE. Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks. Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies.
Psychometric Properties of the Italian Mentalization Questionnaire: Assessing Structural Invariance and Construct Validity

Abstract Mentalization is an important interpersonal ability, necessary for adaptive interpersonal relationships and emotion regulation. Deficits in mentalization have been associated with poor psychological outcomes and have been observed in patients with Borderline Personality Disorder. The Mentalization Questionnaire (MZQ) has been developed as self-report measure of mentalization deficit. The aim of the study was to investigate the dimensionality of the MZQ in a nonclinical sample composed of Italian adults from the general population and to analyze its performance in categorizing individuals with higher risk of borderline symptoms. A non-clinical sample of 1,015 adults (709 women and 306 men) was administered the Italian versions of the MZQ, the Reflective Functioning Questionnaire (RFQ), and a measure of borderline psychopathology. A revised single-factor solution fitted the data well and demonstrated metric invariance across gender. The internal consistency (Ordinal α = 0.87) and stability (r = 0.84) were satisfactory. The MZQ was moderately associated with the RFQ dimensions. The ROC curve analysis showed that the MZQ was able to discriminate satisfactorily people with higher risk for borderline symptomatology from those with lower risk. The MZQ may, therefore, be considered a reliable and valid measure of mentalization for categorizing people at higher risk for borderline pathology.
Prenatal choline supplementation during mouse pregnancy has differential effects in alcohol-exposed fetal organs.

BACKGROUND Fetal alcohol spectrum disorders (FASD) are preventable adverse outcomes consequent to prenatal alcohol exposure. Supplemental choline confers neuroprotection to the alcohol-exposed offspring, but its actions outside the brain are unclear. We previously reported that prenatal exposure of mice to 4.5g/kg alcohol decreased placental weight in females only, but decreased body weight and liver-to-body weight ratio and increased brain-to-body weight ratio in both sexes. Here we test the hypotheses that a lower alcohol dose will elicit similar outcomes, and concurrent choline treatment will mitigate these outcomes. METHODS Pregnant C57BL/6J mice were gavaged with alcohol (3g/kg; Alc) or maltodextrin (MD) from embryonic day (E) 8.5-17.5. Some also received subcutaneous injection of 100mg/kg choline chloride (Alc+Cho, MD+Cho). Outcomes were evaluated on E17.5. RESULTS Alc dams had lower gestational weight gain than MD; this was normalized by choline. In males, Alc decreased placental weight whereas choline increased placental efficiency, and Alc+Cho (vs. MD) trended to further reduce placental weight and increase efficiency. Despite no significant alcohol effects on these measures, choline increased fetal body weight but not brain weight, thus reducing brain-to-body weight ratio in both sexes. This ratio was also lower in the Alc+Cho (vs. MD) fetuses. Alc reduced liver weight and liver-to-body weight ratio; choline did not improve these. Placental weight and efficiency correlated with litter size, whereas placental efficiency correlated with fetal morphometric measurements. CONCLUSIONS Choline prevents the alcohol-reduced gestational weight gain and fetal body weight and corrects fetal brain sparing, consistent with clinical findings of improvements in alcohol-exposed children born to mothers receiving choline supplementation. Importantly, we show that choline enhances placental efficiency in the alcohol-exposed offspring but does not normalize fetal liver growth. Our findings support supplementing choline during pregnancy to mitigate the severity of FASD, and emphasize the need to examine choline's actions in different organ systems.
Space use by the endemic common (weedy) seadragon (Phyllopteryx taeniolatus): influence of habitat and prey.

The weedy seadragon (Phyllopteryx taeniolatus: Syngnathidae) is an iconic fish endemic to the southern coastal waters of Australia. We analysed the habitat preferences and factors influencing microhabitat selection by P. taeniolatus in a population from Kurnell, NSW, Australia. Using field surveys and the resource selection probability function, we determined that P. taeniolatus significantly preferred kelp (Ecklonia radiata) - dominated habitat and avoided rock dominated habitat. We demonstrated P. taeniolatus preferred habitat of between 40 - 80 % coverage of Ecklonia, whilst avoiding areas of < 20 % cover. Furthermore, across all habitats, mysid prey availability significantly influenced P. taeniolatus habitat selection. The strong dependence of P. taeniolatus on Ecklonia habitat shown in this study was previously untested and highlights that reductions in Ecklonia cover under climate change, or impacts from increasing urbanisation, may render seadragon populations vulnerable to declines. This article is protected by copyright. All rights reserved.
Effect of MG‐132 on myofibrillogenesis and the ubiquitination of GAPDH in quail myotubes

In the three‐step myofibrillogenesis model, mature myofibrils are formed through two intermediate structures: premyofibrils and nascent myofibrils. We have recently reported that several inhibitors of the Ubiquitin Proteosome System, for example, MG‐132, and DBeQ, reversibly block progression of nascent myofibrils to mature myofibrils. In this investigation, we studied the effects of MG132 and DBeQ on the expression of various myofibrillar proteins including actin, myosin light and heavy chains, tropomyosin, myomesin, and myosin binding protein‐C in cultured embryonic quail myotubes by western blotting using two loading controls—α‐tubulin and glyceraldehyde 3‐phosphate dehydrogenase (GAPDH). Surprisingly, we found that MG‐132 affected the level of expression of GAPDH but DBeQ did not. Reverse transcription polymerase chain reaction (RT‐PCR) and quantitative reverse transcription‐PCR (qRT‐PCR) showed no significant effect of MG‐132 on GAPDH transcription. Two‐dimensional (2D) western blot analyses with extracts of control and MG‐132‐treated cells using anti‐ubiquitin antibody indicated that MG132‐treated myotubes show a stronger emitter‐coupled logic signal. However, Spot% and Spot volume calculations for all spots from both western blot film signals and matched Coomassie‐stained 2D polyacrylamide gel electrophoresis showed that the intensity of staining in a spot of ~39 kDa protein is 3.5‐fold lower in the gel of MG‐132‐treated extracts. Mass spectrometry analyses identified the ~39 kDa protein as quail GAPDH. Immunohistochemical analysis of fixed MG‐132‐treated myotubes with anti‐GAPDH antibody showed extensive clump formation, which may be analogous to granule formation by stress response factors in MG132‐treated cells. This is the first report on in vivo ubiquitination of GAPDH. This may be essential for the moonlighting (Jeffery, 1999) activity of GAPDH for tailoring stress in myotubes.
Effects of electrospun fiber curcumin on bisphenol A exposed Caco-2 cells

Abstract Curcumin; the major polyphenolic compound, isolated from Curcuma longa L. ; loaded polyvinylpyrrolidone K90 fibers were prepared using electrospinning method. Effectiveness was tested on human colorectal adenocarcinoma cells with the presence of the endocrine disrupter Bisphenol A. Curcumin-loaded fibers were shown to have good physicochemical properties where excellent morphology of the electrospin fibers were formed. With the presence of 8 nM Bisphenol A, 17.37 mM fibers were found to inhibit proliferation in the cells in a dose-dependent manner. Fibers induced a significant increase in malondialdehyde by Thiobarbituric Acid Reactive Substances Assay compared to the control and this effect was supported by the presence of Bisphenol A. Western blot results indicate Super Oxide Dismutase-1 levels were increased by fiber, while Bisphenol A coincubated group resulted in a decrease. Fibers increased the expression of Estrogen Receptor 2, while Estrogen Receptor 1 expression did not change. Estrogen Receptor 2 expression was increased by coincubation with Bisphenol A; indicating a possible role of Estrogen Receptor 2 in the protective effects of fiber. This study presents that fiber had enhanced bioavailability and solubility with increased anticancer effect in human colon adenocarcinoma cells in presence of Bisphenol A; where involved mechanisms are antioxidant system and estrogen receptor expression.
Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

ABSTRACT Numerous studies have manifested that cicular RNA (circRNA) is closely associated with the development of breast cancer (BC), but the specific mechanism has not been fully clarified. The purpose of this study was to investigate the effect of circCNOT2 on BC invasion, migration and epithelial mesenchymal transition (EMT) and its potential molecular mechanism. The results assured that circCNOT2 and Twist Family BHLH Transcription Factor (TWIST1) were elevated in BC, while microrNA (miR)-409-3p was reduced. CircCNOT2 was positively correlated with TWIST1 and negatively correlated with miR-409-3p. Elevated circCNOT2 is associated with poor prognosis of BC. Knockdown circCNOT2 or augmented miR-409-3p could promote apoptosis but repress proliferation, invasion, migration and EMT of BC cells. In addition, overexpression of circCNOT2 or TWIST1 accelerated BC invasion, migration and EMT, which could be reversed by simultaneous transfection of miR-409-3p-mimic. Further dual luciferase reporting and RNA-pull down assay clarified that circCNOT2 acted as a competing endogenous RNA of miR-409-3p to mediate TWIST1 expression. In conclusion, the results of this study suggest that circCNOT2 affects the biological behavior of BC via regulating the miR-409-3p/TWIST1 axis, and may be applied as a potential therapeutic target for BC later.