Miracle-dz/UniFAR-FTUs huggingface dataset:
UDP-Glucose Dehydrogenases: Identification, Expression, and Function Analyses in Upland Cotton (Gossypium hirsutum)

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.
Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions

Diet-induced metabolic endotoxemia is an important factor in the development of many chronic diseases in animals and man. The gut epithelium is an efficient barrier that prevents the absorption of liposaccharide (LPS). Structural changes to the intestinal epithelium in response to dietary alterations allow LPS to enter the bloodstream, resulting in an increase in the plasma levels of LPS (termed metabolic endotoxemia). LPS activates Toll-like receptor-4 (TLR4) leading to the production of numerous pro-inflammatory cytokines and, hence, low-grade systemic inflammation. Thus, metabolic endotoxemia can lead to several chronic inflammatory conditions. Obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) can also cause an increase in gut permeability and potential pharmacological and dietary interventions could be used to reduce the chronic low-grade inflammation associated with endotoxemia.
Quantification of Huntington’s Disease Related Markers in the R6/2 Mouse Model

Huntington’s disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal models that mimic the human pathology are used. The R6/2 mouse as model of HD was already shown to present major neuropathological changes in the caudate putamen and other brain regions, but recently established biomarkers in HD patients were yet not analyzed in these mice. We therefore performed an in-depth analysis of R6/2 mice to establish new and highly translational readouts focusing on Ctip2 as biological marker for motor system-related neurons and translocator protein (TSPO) as a promising readout for early neuroinflammation. Our results validate already shown pathologies like mutant huntingtin aggregates, ubiquitination, and brain atrophy, but also provide evidence for decreased tyrosine hydroxylase and Ctip2 levels as indicators of a disturbed motor system, while vesicular acetyl choline transporter levels as marker for the cholinergic system barely change. Additionally, increased astrocytosis and activated microglia were observed by GFAP, Iba1 and TSPO labeling, illustrating, that TSPO is a more sensitive marker for early neuroinflammation compared to GFAP and Iba1. Our results thus demonstrate a high sensitivity and translational value of Ctip2 and TSPO as new marker for the preclinical evaluation of new compounds in the R6/2 mouse model of HD.
Theoretical Framework for Facilitating Young Musicians’ Learning of Expressive Performance

Since communication and expression are central aspects of music performance it is important to develop a systematic pedagogy of teaching children and teenagers expressiveness. Although research has been growing in this area a comprehensive literature review that unifies the different approaches to teaching young musicians expressiveness has been lacking. Therefore, the aim of this article is to provide an overview of literature related to teaching and learning of expressiveness from music psychology and music education research in order to build a new theoretical framework for teaching and learning expressive music performance in instrumental music lessons with children and teenagers. The article will start with a brief discussion of interpretation and expression in music performance, before providing an overview of studies that investigated teaching and learning of performance expression in instrumental music education with adults and children. On the foundation of this research a theoretical framework for dialogic teaching and learning of expressive music performance will be proposed and the rationale explained. Dialogic teaching can be useful for scaffolding young musicians’ learning of expressivity as open questions can stimulate thinking about the interpretation and may serve to connect musical ideas to the embodied experience of the learner. A “toolkit” for teaching and learning of expressiveness will be presented for practical application in music lessons. In addition, a theoretical model will be proposed to further our understanding of teaching and learning of expressive music performance as a multifaceted and interactive process that is embedded in the context of tutors’ and learners’ experiences and environment. Finally, implications of this framework and suggestions for future research will be discussed.
Effects of Cocaine on Human Glial-Derived Extracellular Vesicles

Background Microglia are important myeloid cells present in the brain parenchyma that serve a surveillance function in the central nervous system. Microglial cell activation results in neuroinflammation that, when prolonged, can disrupt immune homeostasis and neurogenesis. Activated microglia-derived extracellular vesicles (EVs) may be involved in the propagation of inflammatory responses and modulation of cell-to-cell communication. However, a complete understanding of how EVs are regulated by drugs of abuse, such as cocaine, is still lacking. Findings Cocaine exposure reduced human microglial cell (HMC3) viability, decreased expression of CD63 and dectin-1 in HMC3-derived EVs, and increased expression of the apoptotic marker histone H2A.x in HMC3-derived EVs. Conclusion Cocaine impacts HMC3 cell viability and specific EV protein expression, which could disrupt cellular signaling and cell-to-cell communication.
Motivation and Commitment to Sports Practice During the Lockdown Caused by Covid-19

In Spain, the state of alarm declared on March 14, 2020 caused changes in the population in relation to the habits of physical activity and sports practice. This study analyzed what motivational variables predicted the self-efficacy and commitment to sports practice, as well as the differences according to gender, during lockdown and the progressive de-escalation caused by COVID-19, using the theory of self-determination as a theoretical framework. The study sample was conformed of 179 subjects (90 men and 89 women) between 18 and 65 years of age (M = 28.64; SD = 10.28). The Behavioral Regulation in Sport Questionnaire (BRSQ), the Psychological Need Satisfaction in Exercise Scale (PNSE), the Physical Activity Self-Efficacy scale, and the Sport Commitment scale were applied. The most relevant results have showed significant differences in favor of the male gender in terms of levels of controlled motivation and amotivation, as well as higher levels of self-efficacy and basic psychological need of autonomy. Furthermore, the regression analysis has revealed that self-efficacy and current commitment to sports practice were explained by a variance of 57 and 64%, respectively, due to autonomous motivation and the basic psychological need of competence. Therefore, the basic psychological need of competence should be fostered in order to increase the levels of self-determined motivation, self-efficacy, and commitment to sports practice of the population.
Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer

Background Little is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC). Methods eTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined. Results Of the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24–40 years) in the BRCA mutated subgroup and 35 years (range, 21–40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size (P = 0.07) and nuclear grade (P =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy (P = 0.04) and tend to be lower tumor burden (P =0.01). After approximately 5-year median follow-up, the overall survival (OS) (P = 0.021) and breast cancer-specific survival (BCSS) (P = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules. Conclusions These results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.
Long-Term Follow-Up and Optimization of Interleukin-1 Inhibitors in the Management of Monogenic Autoinflammatory Diseases: Real-Life Data from the JIR Cohort

Objectives: The major role of interleukin (IL)-1 in the pathogenesis of hereditary recurrent fever syndromes favored the employment of targeted therapies modulating IL-1 signaling. However the best use of IL1 inhibitors in terms of dosage is difficult to define at present. Methods: In order to better understand the use of IL1 inhibitors in a real-life setting, our study assessed the dosage regimens of French patients with one of the four main hereditary recurrent fever syndromes (Familial Mediterranean Fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin associated periodic fever (CAPS) and mevalonate kinase deficiency). The patients were retrieved retrospectively from the JIR cohort, an international platform gathering data of patients with pediatric inflammatory diseases. Results: Forty five patients of the JIR cohort with a hereditary recurrent fever syndrome had received at least once an IL1 inhibitor (anakinra or canakinumab). Of these, 43% received a lower dosage than the one suggested in the product recommendations, regardless of the type of the IL1 inhibitor. Especially patients with FMF and TRAPS seemed to need lower treatment regimens; in our cohort none of the FMF or TRAPS patients received an intensified dose of IL-inhibitor. On-demand treatment with a short half-life IL-1 inhibitor has also been used successfully for some patients with one of these two conditions The standard dose was given to 42% of the patients; whereas an intensified dose of IL-1 inhibitors was given to 15% of the patients (44% of CAPS patients and 17% of mevalonate kinase deficiency patients). In our cohort each individual patient’s need for treatment seemed highly variable, ranging from on demand treatment regimens to intensified dosage maintenance therapies depending on the activity and the severity of the underlying disease. Conclusion: IL-1 inhibitors are a good treatment option for patients with a hereditary recurrent fever syndrome, but the individual need of the dosage of IL-1 inhibitors to control the disease effectively seems highly variable. Severity, activity but also the type of the underlying disease, belong to the parameters underpinning the treat-to-target strategy implemented in an everyday life practice.
What Drives Life-History Variation in the Livebearing Fish Poeciliopsis prolifica? An Assessment of Multiple Putative Selective Agents

Life-history traits are directly linked to fitness, and therefore, can be highly adaptive. Livebearers have been used as models for understanding the evolution of life histories due to their wide diversity in these traits. Several different selective pressures, including population density, predation, and resource levels, can shape life-history traits. However, these selective pressures are usually considered independently in livebearers and we lack a clear understanding of how they interact in shaping life-history evolution. Furthermore, selective pressures such as interspecific competition are rarely considered as drivers of life-history evolution in poeciliids. Here we test the simultaneous effects of several potential selective pressures on life-history traits in the livebearing fish Poeciliopsis prolifica. We employ a multi-model inference approach. We focus on four known agents of selection: resource availability, stream velocity, population density, and interspecific competition, and their effect on four life-history traits: reproductive allocation, superfetation, number of embryos, and individual embryo size. We found that models with population density and interspecific competition alone were strongly supported in our data and, hence, indicated that these two factors are the most important selective agents for most life-history traits, except for embryo size. When population density and interspecific competition increase there is an increase in each of the three life-history traits (reproductive allocation, superfetation, and number of embryos). For individual embryo size, we found that all single-agent models were equivalent and it was unclear which selective agent best explained variation. We also found that models that included population density and interspecific competition as direct effects were better supported than those that included them as indirect effects through their influence on resource availability. Our study underscores the importance of interspecific competitive interactions on shaping life-history traits and suggests that these interactions should be considered in future life-history studies.
Participating in Online Museum Communities: An Empirical Study of Taiwan’s Undergraduate Students

With the worldwide spread of the Internet, human activity has become permeated by digital media, which shapes communication and interaction and speeds up the improvement of the experience and diffusion of museum exhibitions. Contemporary museums must understand their audiences, especially with respect to online preferences and surfing involvement experiences. Museums are changing in an effort to attract young netizens to access and use museum resources. Virtual museums are increasingly using digital exhibitions to preserve and apply their collections and establishing online community platforms to interact with young people. This study investigates the underlying mechanism of online community characteristics that enhance audiences’ emotional resonance and involvement. Results from a questionnaire survey (N = 1168) of Taiwan undergraduate students show that perceived relevance and esteem improve their emotional resonance, which can attract new people and maintain existing relationships within their communities. Following flow theory, maintaining community relationship characteristics increases emotional resonance, which, in turn, enhances user involvement, but we found only small significant effects of emotional resonance on involvement. These findings illuminate the mechanism of the attitudinal relationship building and maintenance for online museum communities and advance the practical contributions of online museum community use and effects.
Progression and Outcomes of Non-dysfunctional Bicuspid Aortic Valve: Longitudinal Data From a Large Korean Bicuspid Aortic Valve Registry

Background: Using echocardiographic surveillance, many patients are diagnosed with bicuspid aortic valve (BAV) without significant valve dysfunction. Limited data are available regarding the progression and outcomes of non-dysfunctional BAV. Methods and Results: We investigated 1,307 BAV patients (984 male, mean age 56 years) diagnosed from Jan 2003 through Dec 2018 in a single tertiary center. Seven hundred sixty-one patients underwent follow-up echocardiography at ≥1 year post-diagnosis. Non-dysfunctional BAV was defined as BAV without moderate aortic stenosis (AS) or aortic regurgitation (AR). The presence of aortopathy was defined as an ascending aorta diameter >37mm. Progression to significant BAV dysfunction, progression to severe aortopathy (ascending aorta diameter ≥45mm), and incidence of valve or aorta operation were analyzed. One hundred eighty-seven (25%) patients showed non-dysfunctional BAV. Among them, 104 (56%) had mild AS or AR, and 81 (43%) had aortopathy at indexed echocardiography. At 6.0 ± 3.8 years post-diagnosis, 56 (29%) progressed to dysfunctional BAV, 28 (15%) progressed to severe aortopathy, 22 (12%) underwent valve operation, and 19 (10%) experienced aorta operation. Eighty-nine percent of patients with normal BAV function and 61% of patients with mild AS or AR maintained non-dysfunctional BAV. More patients with aortopathy progressed to severe aortopathy (35 vs. 0% without aortopathy, p < 0.001), with a higher incidence of aorta operation (21 vs. 2%, p < 0.001). Conclusions: In patients with non-dysfunctional BAV, initial BAV function and degree of aorta dilatation might be important for progression and outcomes. Patients without any dysfunction or aortopathy tend to maintain good structure and function for 6 years.
Functional Diversity in Ferns Is Driven by Species Richness Rather Than by Environmental Constraints

Functional traits determine how species interact with their abiotic and biotic environment. In turn, functional diversity describes how assemblages of species as a whole are adapted to their environment, which also determines how they might react to changing conditions. To fully understand functional diversity, it is fundamental to (a) disentangle the influences of environmental filtering and species richness from each other, (b) assess if the trait space saturates at high levels of species richness, and (c) understand how changes in species numbers affect the relative importance of the trait niche expansion and packing. In the present study, we determined functional diversity of fern assemblages by describing morphological traits related to resource acquisition along four tropical elevational transects with different environmental conditions and species richness. We used several functional diversity indices and their standardized effect size to consider different aspects of functional diversity. We contrasted these aspects of functional diversity with climate data and species richness using linear models and linear mixed models. Our results show that functional morphological trait diversity was primarily driven by species richness and only marginally by environmental conditions. Moreover, increasing species richness contributed progressively to packing of the morphological niche space, while at the same time decreasing morphological expansion until a saturation point was reached. Overall, our findings suggest that the density of co-occurring species is the fundamental driving force of morphological niche structure, and environmental conditions have only an indirect influence on fern resource acquisition strategies.
Bioenergetic Inhibitors: Antibiotic Efficacy and Mechanisms of Action in Mycobacterium tuberculosis

Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery. Targeting the electron transport chain (ETC) and oxidative phosphorylation machinery promises not only to kill growing cells but also metabolically dormant bacilli that are inherently more drug tolerant. Over the last two decades, a broad array of drugs targeting various ETC components have been developed. Here, we provide a focused review of the current state of art of bioenergetic inhibitors of Mtb with an in-depth analysis of the metabolic and bioenergetic disruptions caused by specific target inhibition as well as their synergistic and antagonistic interactions with other drugs. This foundation is then used to explore the reigning theories on the mechanisms of antibiotic-induced cell death and we discuss how bioenergetic inhibitors in particular fail to be adequately described by these models. These discussions lead us to develop a clear roadmap for new lines of investigation to better understand the mechanisms of action of these drugs with complex mechanisms as well as how to leverage that knowledge for the development of novel, rationally-designed combination therapies to cure TB.