Miracle-dz/UniFAR-FTUs huggingface dataset:
Autonomic dysfunction, cardio‐pulmonary exercise testing and masked heart failure with preserved ejection fraction in non‐severe chronic obstructive pulmonary disease

Autonomic dysfunction (AD) and cardiopulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive.
Transient de-protonation of the chromophore affects protein dynamics proximal and distal to the linear tetrapyrrole chromophore in phytochrome Cph1.

Phytochromes are biological red/far-red light sensors found in many organisms. Prototypical phytochromes including Cph1 from the cyanobacterium Synechocystis 6803 act as photochemical switches that interconvert between stable red (Pr) and metastable far-red (Pfr) - absorbing states induced by photoisomerization of the bilin chromophore. The connection between photoconversion and the cellular output signal involves light-mediated global structural changes in the interaction between the photosensory module (PAS-GAF-PHY) and the C-terminal transmitter (output) module, usually a histidine kinase, as in the case of Cph1. The chromophore deprotonates transiently during the Pr → Pfr photoconversion in association with extensive global structural changes required for signal transmission. Here, we performed equilibrium studies in the Pr-state, involving pH-titration of the linear tetrapyrrole chromophore in different Cph1 constructs, and measurement of pH-dependent structural changes at various positions in the protein using picosecond time-resolved fluorescence anisotropy. The fluorescent reporter group was attached at positions 371 (PHY domain), 305 (GAF domain) and 120 (PAS domain), as well as at sites in the PAS-GAF bidomain. We show direct correlation of chromophore deprotonation with pH-dependent conformational changes in the various domains. Our results suggest that chromophore deprotonation is closely associated with a higher protein mobility (conformational space) both in proximal and distal protein sites, implying a causal relationship that might be important for the global large protein arrangements and thus intramolecular signal transduction.
Growth and Maturation in Development: A Fly’s Perspective

In mammals like humans, adult fitness is improved due to resource allocation, investing energy in the developmental growth process during the juvenile period, and in reproduction at the adult stage. Therefore, the attainment of their target body height/size co-occurs with the acquisition of maturation, implying a need for coordination between mechanisms that regulate organismal growth and maturation timing. Insects like Drosophila melanogaster also define their adult body size by the end of the juvenile larval period. Recent studies in the fly have shown evolutionary conservation of the regulatory pathways controlling growth and maturation, suggesting the existence of common coordinator mechanisms between them. In this review, we will present an overview of the significant advancements in the coordination mechanisms ensuring developmental robustness in Drosophila. We will include (i) the characterization of feedback mechanisms between maturation and growth hormones, (ii) the recognition of a relaxin-like peptide Dilp8 as a central processor coordinating juvenile regeneration and time of maturation, and (iii) the identification of a novel coordinator mechanism involving the AstA/KISS system.
Effects of collaboration on the qualities of autobiographical recall in strangers, friends, and siblings: both remembering partner and communication processes matter

ABSTRACT Recalling autobiographical memories with others can influence the quality of recall, but little is known about how features of the group influence memory outcomes. In two studies, we examined how the products and processes of autobiographical recall depend on individual vs. collaborative remembering and the relationship between group members. In both studies, dyads of strangers, friends, and siblings recalled autobiographical events individually (elicitation), then either collaboratively or individually (recall). Study 1 involved typing memory narratives; Study 2 involved recalling aloud. We examined shifts in vividness, emotionality, and pronoun use within memory narratives produced by different relationship types. In Study 2, we also coded collaborative dyads’ “collaborative processes” or communication processes. In Study 1, all relationships showed decreased positive emotion and I-pronouns and increased negative emotion within collaboratively-produced memory narratives. In Study 2, all relationships showed increased vividness, reduced emotionality and positive and negative emotion, and increased I- and we-pronouns within collaboratively-produced memory narratives. However, strangers used collaborative processes differently from friends and siblings. Some collaborative processes were associated with memory qualities. Across studies, collaboration influenced memory quality more than did relationship type, but relationship type influenced dyads’ recall dynamics. These findings indicate the complexity of social influences on memory.
Profiling the ToxCast library with a pluripotent human (H9) stem cell line-based biomarker assay for developmental toxicity.

The Stemina devTOX quickPredict platform (devTOXqP) is a human pluripotent stem cell-based assay that predicts the developmental toxicity potential based on changes in cellular metabolism following chemical exposure [Palmer et al. 2013]. Using this assay, we screened 1065 ToxCast Phase I and II chemicals in single-concentration or concentration-response for the targeted biomarker (ratio of ornithine to cystine secreted or consumed from the media). The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast_STM dataset include: [1] 19% of 1065 chemicals yielded a prediction of developmental toxicity; [2] assay performance reached 79% to 82% accuracy with high specificity (>84%) but modest sensitivity (<67%) when compared to in vivo animal models of human prenatal developmental toxicity; [3] sensitivity improved as more stringent weight of evidence requirements were applied to the animal studies; and [4] statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models.
The Role of Emotional Intelligence and Sociocultural Adjustment on Migrants’ Self-reported Mental Well-Being in Spain: A 14 Month Follow-Up Study

The analysis of mental and psychological health is a relevant public issue in modern societies. Migration is a process that may have a lasting impact on a person’s mental well-being. In this study, perceived health, emotional intelligence, sociocultural adjustment and the participants’ perceived general situation, not only economical, were analyzed to attest their impact on psychological distress as a measure of mental well-being. Sixty-three migrants from Romania and Ecuador were contacted twice during a 14 month period in a middle-sized Spanish city. Attrition analyses show no significant differences in perceived psychological distress between those who participated only one time or who participated in both waves. Less psychological distress is related to less attention to one’s feelings and higher mood repair in both data waves. Stronger behavioral adjustment is also linked to less distress. Less distress in time 1 led to better perceived health, sociocultural adjustment and a perception of a better general situation in Spain in comparison to their home country in time 2. In general, more attention to negative feelings triggered more perceived psychological distress, whereas mood repair elicited less psychological distress, in time 2. The relevance of understanding the impact of emotional intelligence to health promotion programs with migrants is discussed.
Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension

ABSTRACT Introduction: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling of small pulmonary arteries leading to increased pulmonary arterial pressure. Existing treatments acts to normalize vascular tone via three signaling pathways: the prostacyclin, the endothelin-1, and the nitric oxide. Although over the past 20 years, there has been considerable progress in terms of treatments for PAH, the disease still remains incurable with a disappointing prognosis. Areas covered: This review summarizes the pathophysiology of PAH, the advantages and disadvantages of the inhalation route, and assess the relative advantages various inhaled therapies for PAH. The recent studies concerning the development of controlled-release drug delivery systems loaded with available anti-PAH drugs have also been summarized. Expert opinion: The main obstacles of current pharmacotherapies of PAH are their short half-life, stability, and formulations, resulting in reducing the efficacy and increasing systemic side effects and unknown pathogenesis of PAH. The pulmonary route has been proposed for delivering anti-PAH drugs to overcome the shortcomings. However, the application of approved inhaled anti-PAH drugs is limited. Inhalational delivery of controlled-release nanoformulations can overcome these restrictions. Extensive studies are required to develop safe and effective drug delivery systems for PAH patients.
Variations in the morphology of stylomastoid foramen: A possible solution to the conundrum of unexplained cases of Bell's palsy.

BACKGROUND Stylomastoid foramen is the terminal part of facial canal and is the exit gateway for facial nerve from skull base. We hypothesized that anatomical variations of this foramen could be a risk factor for the injury of facial nerve resulting in unilateral facial nerve paralysis or Bell's palsy. Hence the present study was conducted to study the variations in size and shape of stylomastoid foramen in dry adult human skulls. MATERIALS AND METHODS The study was conducted on 37 dry adult human skulls of unknown age and sex. High resolution images of the skulls under study were processed by ImageJ software and observations were undertaken. RESULTS Total 8 variations of stylomastoid foramen were observed in terms of shape. The common variants were round, oval and square (present in 83.79% skulls on right side and 81.07% skulls on left side), whereas the rare variants were triangular, rectangular, serrated, bean and irregular. It was noted that stylomastoid foramen were associated with extensions (45.95% skulls) and also adjacent foramen (18.92% skulls). Exclusively unilateral observations included bifurcation of foramen (16.22% skulls), foramen situated deep inside skull groove (5.41% skulls) and foramen interrupted by bony spur (2.7% skulls). No significant differences were observed between the mean diameters (antero-posterior and transverse) of the stylomastoid foramen. CONCLUSIONS The unilateral variations along with rare variations in terms of shape such as serrated, bean and irregular foramen (which were also unilateral findings) could be potential risk factors towards injury of facial nerve at the point of exit from skull base leading to Bell's palsy.
Divergent selection and genetic introgression shape the genome landscape of heterosis in hybrid rice

Significance The application of heterosis (hybrid vigor) in hybrid rice since the 1970s has tremendously improved rice productivity worldwide. But how breeders construct hybrid parents to obtain hybrid rice heterosis remains unclear. Here, by genome analysis, we found that breeders introduced different introgressed exogenous genomes of other rice subpopulations to construct male and female parents. The differentiated introgression in parents shaped heterotic loci in the hybrid rice. Genetic origin analysis revealed that heterotic loci existed in wild rice and were divergently selected among rice subpopulations. Our results traced the origin of heterotic loci of hybrid rice and uncovered genetic change of heterotic loci across rice evolution and breeding stages, which could facilitate the future breeding of more superior hybrid rice varieties. The successful application of heterosis in hybrid rice has dramatically improved rice productivity, but the genetic mechanism for heterosis in the hybrid rice remains unclear. In this study, we generated two populations of rice F1 hybrids with present-day commercial hybrid parents, genotyped the parents with 50k SNP chip and genome resequencing, and recorded the phenotype of ∼2,000 hybrids at three field trials. By integrating these data with the collected genotypes of ∼4,200 rice landraces and improved varieties that were reported previously, we found that the male and female parents have different levels of genome introgressions from other rice subpopulations, including indica, aus, and japonica, therefore shaping heterotic loci in the hybrids. Among the introgressed exogenous genome, we found that heterotic loci, including Ghd8/DTH8, Gn1a, and IPA1 existed in wild rice, but were significantly divergently selected among the rice subpopulations, suggesting these loci were subject to environmental adaptation. During modern rice hybrid breeding, heterotic loci were further selected by removing loci with negative effect and fixing loci with positive effect and pyramid breeding. Our results provide insight into the genetic basis underlying the heterosis of elite hybrid rice varieties, which could facilitate a better understanding of heterosis and rice hybrid breeding.
β-Arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates

Significance Frontotemporal lobar degeneration (FTLD) is second only to Alzheimer’s disease as a cause of dementia, and we find the scaffolding protein β-arrestin2 is elevated in human brains with this condition, and is responsible for accumulation of pathological tau tangles. Increased β-arrestin2 impairs tau clearance and promotes tau aggregation by impeding the autophagy cargo carrier p62/SQSTM1. Such activity requires β-arrestin2 in its oligomeric form, an assembly state that is not involved with receptor binding. Virus delivered gene therapy to the brain with dominant-negative mutant β-arrestin2s ablates pathologic tau in neurons of a mouse model of FTLD-tau, revealing a strategy to mitigate tauopathy by targeting β-arrestin2 oligomerization. Multiple G protein-coupled receptors (GPCRs) are targets in the treatment of dementia, and the arrestins are common to their signaling. β-Arrestin2 was significantly increased in brains of patients with frontotemporal lobar degeneration (FTLD-tau), a disease second to Alzheimer’s as a cause of dementia. Genetic loss and overexpression experiments using genetically encoded reporters and defined mutant constructs in vitro, and in cell lines, primary neurons, and tau P301S mice crossed with β-arrestin2−/− mice, show that β-arrestin2 stabilizes pathogenic tau and promotes tau aggregation. Cell and mouse models of FTLD showed this to be maladaptive, fueling a positive feedback cycle of enhanced neuronal tau via non-GPCR mechanisms. Genetic ablation of β-arrestin2 markedly ablates tau pathology and rescues synaptic plasticity defects in tau P301S transgenic mice. Atomic force microscopy and cellular studies revealed that oligomerized, but not monomeric, β-arrestin2 increases tau by inhibiting self-interaction of the autophagy cargo receptor p62/SQSTM1, impeding p62 autophagy flux. Hence, reduction of oligomerized β-arrestin2 with virus encoding β-arrestin2 mutants acting as dominant-negatives markedly reduces tau-laden neurofibrillary tangles in FTLD mice in vivo. Reducing β-arrestin2 oligomeric status represents a new strategy to alleviate tau pathology in FTLD and related tauopathies.
New Ionic Carbosilane Dendrons Possessing Fluorinated Tails at Different Locations on the Skeleton

The fluorination of dendritic structures has attracted special attention in terms of self-assembly processes and biological applications. The presence of fluorine increases the hydrophobicity of the molecule, resulting in a better interaction with biological membranes and viability. In addition, the development of 19F magnetic resonance imaging (19F-MRI) has greatly increased interest in the design of new fluorinated structures with specific properties. Here, we present the synthesis of new water-soluble fluorinated carbosilane dendrons containing fluorinated chains in different positions on the skeleton, focal point or surface, and their preliminary supramolecular aggregation studies. These new dendritic systems could be considered as potential systems to be employed in drug delivery or gene therapy and monitored by 19F-MRI.
A Straightforward Approach to Engineer Vascularized Adipose Tissue Using Microvascular Fragments.

There is a need to overcome the donor-site morbidity and loss of volume over time that accompanies the current clinical approaches to treat soft tissue defects caused by disease and trauma. The development of bioactive constructs that can regenerate adipose tissue have made great progress towards addressing the limitations of current therapies, but their lack of vascularization and ability to meet the significant dimension requirements of tissue defects limits their clinical translatability. Microvascular fragments (MVFs) can form extensive vascular networks and contain resident cells that have the ability to differentiate into adipocytes. Therefore, the objective of this study was to determine if vascularized adipose tissue could be engineered using a fibrin-based hydrogel containing MVFs as the sole source of microvessels and adipocyte-forming cells. The potential for MVFs from different fat depots (epididymal, inguinal, and subcutaneous) to form microvascular networks and generate adipocytes when exposed to growth media, adipogenic media, or when treated with growth media prior to adipogenic induction (i.e., they were allowed to "pre-sprout" prior to adipogenic induction) was evaluated. MVFs treated with adipogenic induction media, both with and without pre-sprouting, contained lipid droplets, had an increase in expression levels of genes associated with adipogenesis (adiponectin and Fatty Acid Synthase (FAS)), and had an increased rate of lipolysis. MVFs allowed to pre-sprout before adipogenic media treatment maintained their ability to form vascular networks while maintaining an elevated lipid content, adipogenic gene expression, and lipolysis rate. Collectively, these results support the contention that MVFs can serve as the sole source of biologic material for creating a vascularized adipose tissue scaffold. Impact Statement Microvascular fragments (MVFs) have both the ability to form extensive vascular networks and function as a source of adipocytes. These phenomena were exploited as vascularized adipose tissue was generated by first allowing for a period of angiogenesis prior to the adipogenic induction. This strategy has the ability to provide a means of both improving soft tissue reconstruction while also serving as a model to better understand adipose tissue expansion.
Why East Asians but not South Asians are underrepresented in leadership positions in the United States

Significance Whereas extensive research has examined the “glass ceiling” faced by women, little research has examined the “bamboo ceiling,” whereby Asians appear disproportionately underrepresented in leadership positions in the United States. To investigate the mechanisms and scope of this problem, we compared the two largest Asian subgroups: East Asians and South Asians. Across nine studies (n = 11,030), East Asians were less likely than South Asians and whites to attain leadership positions, whereas South Asians outperformed whites. The leadership attainment gap between East Asians and South Asians was consistently explained by cultural differences in assertiveness, but not by prejudice or motivation. To leverage diverse leadership talent, organizations should understand the differences among different cultural groups and diversify the prototype of leadership. Well-educated and prosperous, Asians are called the “model minority” in the United States. However, they appear disproportionately underrepresented in leadership positions, a problem known as the “bamboo ceiling. ” It remains unclear why this problem exists and whether it applies to all Asians or only particular Asian subgroups. To investigate the mechanisms and scope of the problem, we compared the leadership attainment of the two largest Asian subgroups in the United States: East Asians (e.g., Chinese) and South Asians (e.g., Indians). Across nine studies (n = 11,030) using mixed methods (archival analyses of chief executive officers, field surveys in large US companies, student leader nominations and elections, and experiments), East Asians were less likely than South Asians and whites to attain leadership positions, whereas South Asians were more likely than whites to do so. To understand why the bamboo ceiling exists for East Asians but not South Asians, we examined three categories of mechanisms—prejudice (intergroup), motivation (intrapersonal), and assertiveness (interpersonal)—while controlling for demographics (e.g., birth country, English fluency, education, socioeconomic status). Analyses revealed that East Asians faced less prejudice than South Asians and were equally motivated by work and leadership as South Asians. However, East Asians were lower in assertiveness, which consistently mediated the leadership attainment gap between East Asians and South Asians. These results suggest that East Asians hit the bamboo ceiling because their low assertiveness is incongruent with American norms concerning how leaders should communicate. The bamboo ceiling is not an Asian issue, but an issue of cultural fit.
Impact of flaxseed supplementation on plasma lipoprotein(a) concentrations: A systematic review and meta‐analysis of randomized controlled trials

The aim of the study was to investigate the impact of supplementation with flaxseed on plasma lipoprotein(a) [Lp(a)] levels through a systematic review and meta‐analysis of eligible randomized placebo‐controlled trials. PubMed, Scopus, Cochrane Library, and ISI Web of Science were searched for randomized controlled trials (RCTs) which have been published up to November 2019. RCTs that investigated the effect of flaxseed supplementation on plasma Lp(a) levels in adults were included for final analysis. The random effects model was used for calculating the overall effects. Meta‐analysis of 7 selected RCTs with 629 individuals showed significant lowering effect of flaxseed supplementation on Lp(a) (MD −2.06 mg/dl; 95% CI: −3.846, −0.274, p = .024), without considerable heterogeneity between studies (p = .986, I2 = 0%). Subgroup analysis also revealed that longer duration only showed significant lowering effect of flaxseed supplementation on Lp(a). This meta‐analysis has shown that flaxseed supplementation might significantly decrease plasma Lp(a) levels. Future well‐designed and long‐term clinical trials are required to confirm these results.