Miracle-dz/UniFAR-FTUs huggingface dataset:
Tree size drives diversity and community structure of microbial communities on the bark of beech (Fagus sylvatica)

Tree bark constitutes ideal habitat for microbial communities, because it is a stable substrate, rich in micro-niches. Bacteria, fungi, and terrestrial microalgae together form microbial communities, which in turn support more bark-associated organisms, such as mosses, lichens, and invertebrates, thus contributing to forest biodiversity. We have a limited understanding of the diversity and biotic interactions of the bark-associated microbiome, as investigations have mainly focussed on agriculturally relevant systems and on single taxonomic groups. Here we implemented a multi-kingdom metabarcoding approach to analyse diversity and community structure of the green algal, bacterial, and fungal components of the bark-associated microbial communities of beech, the most common broadleaved tree of Central European forests. We identified the most abundant taxa, hub taxa, and co-occurring taxa. We found that tree size (as a proxy for age) is an important driver of community assembly, suggesting that environmental filtering leads to less diverse fungal and algal communities over time. Conversely, forest management intensity had negligible effects on microbial communities on bark. Our study suggests the presence of undescribed, yet ecologically meaningful taxa, especially in the fungi, and highlights the importance of bark surfaces as a reservoir of microbial diversity. Our results constitute a first, essential step towards an integrated framework for understanding microbial community assembly processes on bark surfaces, an understudied habitat and neglected component of terrestrial biodiversity. Finally, we propose a cost-effective sampling strategy to study bark-associated microbial communities across large spatial or environmental scales.
Environment Constrains Fitness Advantages of Division of Labor in Microbial Consortia Engineered for Metabolite Push or Pull Interactions

Most naturally occurring microorganisms persist in consortia where metabolic interactions are common and often essential to ecosystem function. This study uses synthetic ecology to test how different cellular interaction motifs influence performance properties of consortia. ABSTRACT Fitness benefits from division of labor are well documented in microbial consortia, but the dependency of the benefits on environmental context is poorly understood. Two synthetic Escherichia coli consortia were built to test the relationships between exchanged organic acid, local environment, and opportunity costs of different metabolic strategies. Opportunity costs quantify benefits not realized due to selecting one phenotype over another. The consortia catabolized glucose and exchanged either acetic or lactic acid to create producer-consumer food webs. The organic acids had different inhibitory properties and different opportunity costs associated with their positions in central metabolism. The exchanged metabolites modulated different consortial dynamics. The acetic acid-exchanging (AAE) consortium had a “push” interaction motif where acetic acid was secreted faster by the producer than the consumer imported it, while the lactic acid-exchanging (LAE) consortium had a “pull” interaction motif where the consumer imported lactic acid at a comparable rate to its production. The LAE consortium outperformed wild-type (WT) batch cultures under the environmental context of weakly buffered conditions, achieving a 55% increase in biomass titer, a 51% increase in biomass per proton yield, an 86% increase in substrate conversion, and the complete elimination of by-product accumulation all relative to the WT. However, the LAE consortium had the trade-off of a 42% lower specific growth rate. The AAE consortium did not outperform the WT in any considered performance metric. Performance advantages of the LAE consortium were sensitive to environment; increasing the medium buffering capacity negated the performance advantages compared to WT. IMPORTANCE Most naturally occurring microorganisms persist in consortia where metabolic interactions are common and often essential to ecosystem function. This study uses synthetic ecology to test how different cellular interaction motifs influence performance properties of consortia. Environmental context ultimately controlled the division of labor performance as shifts from weakly buffered to highly buffered conditions negated the benefits of the strategy. Understanding the limits of division of labor advances our understanding of natural community functioning, which is central to nutrient cycling and provides design rules for assembling consortia used in applied bioprocessing.
Therapeutic Interruption of T Cell Development Generates High-Affinity T Cells That Escape Exhaustion and Improve Cancer Immunotherapy

Availability of effective anti-tumor T cells is limited by cancer immunoediting, which depletes neoantigens, and central tolerance, which eliminates developing T cells with high-affinity T cell receptors (TCRs) against tumor self-antigens. Remaining tumor-reactive T cells are often exhausted after immune checkpoint blockade (ICB). Whether endogenous T cells with high- affinity TCRs against tumor self-antigens can be generated to circumvent exhaustion and reject neoantigen-poor tumors is unclear. We show that transiently interrupting central tolerance through RANKL blockade unleashes T cells possessing TCRs with self-reactive features that enable ICB to reject poorly immunogenic tumors. Upon recognition of tumor self-antigens, these T cells exhibit enhanced TCR signaling, enrichment in NFAT/AP-1 genes, and lymph node priming. Consequently, memory-precursor T cells against tumor self-antigens are generated, avoid exhaustion, and become effector-memory cells with transcriptional features associated with clinical ICB response. Thus, interrupting central tolerance provides T cells with tumor- directed autoreactivity that avoid exhaustion and improve immunotherapy.
Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p<0.001) but not in KO. Notably, exercise increased trabecular BV/TV in both (+31%, KO-E vs KO, p=0.004; +14%, WT-E vs WT, p=0.006). The presence and distribution of BMAT in SEIPIN KO, though lower than WT, is unexpected and points to a uniqueness of this depot. That trabecular bone increases were achievable in both KO and WT, despite a difference in BMAT quantity/distribution, points to potential metabolic flexibility during exercise-induced skeletal anabolism.
Polysubstance Use Patterns Among High Dose Benzodiazepine Users: A Latent Class Analysis and Differences Between Male and Female Use

Benzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1. The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales.
Effects of an SEL Program in a Diverse Population of Low Achieving Secondary Education Students

Adolescents’ social-emotional skills are associated with positive outcomes in psychosocial health and success in education and work. In this study, we examined the effectiveness of Skills4Life, a Social Emotional Learning program for preparatory vocational secondary education aimed at enhancing self-awareness, social awareness, self-management, relationship skills, and responsible decision making. Low-achieving students with additional educational needs participated in a quasi-experimental study, with an intervention (N = 465) and a control group (N = 274). We assessed the outcomes on social-emotional skills and psychosocial health using self-report questionnaires at pre-test (T0), after finishing the basic module (T1), and after finishing the internship module (T2). Multi-level regression analyses indicated no overall effects on the outcomes at T1 and T2. After completing the entire program at T2, students from non-western backgrounds had significantly unfavorable lower scores on social awareness and relationship skills. Positive effects were found on self-management and preparation for internships in students taught by experienced professional trainers compared to students taught by regular classroom teachers at T2. Alterations in the socio-cultural approach of the Skills4Life program and teacher training are needed to support all students in developing the social-emotional skills that they need for success at school and the workplace.
A Scoping Review of Barriers and Facilitators Affecting the Lives of People With Disabilities During COVID-19

Purpose This scoping review aimed to identify the barriers and facilitators to everyday activities and social participation of people with a disability (PWD) during the first wave of the COVID-19 pandemic. Methods The search terms (disability and COVID-19) were used in four databases: CINAHL, Medline (Ovid), EMBASE and Web of Science. The search conducted from January 2019 to September 22, 2020, identified 465 peer reviewed articles and abstracts and were screened in Covidence software. Studies were included if they had the terms “COVID-19” and “disability,” were published in English, and specifically examined how COVID-19 impacted the daily lives of PWD. Exclusion criteria included: disability as a symptom or result of COVID-19, the health outcomes when PWD acquired COVID-19, disability leave for someone who is sick and the risk of acquiring the disease for PWD. 74 articles met the inclusion criteria and were analyzed via data charting. Charting began with existing barriers and facilitators identified by the World Health Organization and new barriers and facilitators, that emerged from the texts were added during this process. Results The barriers that emerged included: access to information, ease of communication, financial impacts, mental health impacts, access to essential services, physical safety, educational challenges, and changes to care and rehabilitation. Significant facilitators included: changes to care and rehabilitation, new innovations, social and familial support and inclusive policy measures. Conclusion COVID-19 exacerbated existing challenges in the lives of PWD and raised new quality of life concerns. Findings also demonstrate that policy makers, health care professionals and others continually support PWD in times of crisis.
Exploring Neurofilament Light Chain and Exosomes in the Genetic Forms of Frontotemporal Dementia

Differential diagnosis of neurological disorders and their subtype classification are challenging without specific biomarkers. Genetic forms of these disorders, typified by an autosomal dominant family history, could offer a window to identify potential biomarkers by exploring the presymptomatic stages of the disease. Frontotemporal dementia (FTD) is the second cause of dementia with an age of onset < 65, and its most common mutations are in GRN, C9orf72, and MAPT genes. Several studies have demonstrated that the main proteins involved in FTD pathogenesis can be secreted in exosomes, a specific subtype of extracellular vesicles able to transfer biomolecules between cells avoiding cell-to-cell contact. Neurofilament light chain (NfL) levels in central nervous system have been advocated as biomarkers of axonal injury. NfL concentrations have been found increased in FTD and have been related to disease severity and prognosis. Little information on the relationship between NfL and exosomes in FTD has been collected, deriving mainly from traumatic brain injury. Current review deals with this matter in the attempt to provide an updated discussion of the role of NfL and exosomes as biomarkers of genetic forms of FTD.
Case Report: Laser Ablation Guided by State of the Art Source Imaging Ends an Adolescent's 16-Year Quest for Seizure Freedom

Epilepsy surgery is the most effective therapeutic approach for children with drug resistant epilepsy (DRE). Recent advances in neurosurgery, such as the Laser Interstitial Thermal Therapy (LITT), improved the safety and non-invasiveness of this method. Electric and magnetic source imaging (ESI/MSI) plays critical role in the delineation of the epileptogenic focus during the presurgical evaluation of children with DRE. Yet, they are currently underutilized even in tertiary epilepsy centers. Here, we present a case of an adolescent who suffered from DRE for 16 years and underwent surgery at Cook Children's Medical Center (CCMC). The patient was previously evaluated in a level 4 epilepsy center and treated with multiple antiseizure medications for several years. Presurgical evaluation at CCMC included long-term video electroencephalography (EEG), magnetoencephalography (MEG) with simultaneous conventional EEG (19 channels) and high-density EEG (256 channels) in two consecutive sessions, MRI, and fluorodeoxyglucose - positron emission tomography (FDG-PET). Video long-term EEG captured nine focal-onset clinical seizures with a maximal evolution over the right frontal/frontal midline areas. MRI was initially interpreted as non-lesional. FDG-PET revealed a small region of hypometabolism at the anterior right superior temporal gyrus. ESI and MSI performed with dipole clustering showed a tight cluster of dipoles in the right anterior insula. The patient underwent intracranial EEG which indicated the right anterior insular as seizure onset zone. Eventually LITT rendered the patient seizure free (Engel 1; 12 months after surgery). Retrospective analysis of ESI and MSI clustered dipoles found a mean distance of dipoles from the ablated volume ranging from 10 to 25 mm. Our findings highlight the importance of recent technological advances in the presurgical evaluation and surgical treatment of children with DRE, and the underutilization of epilepsy surgery in children with DRE.
Potassium Titanate Assembled Titanium Dioxide Nanotube Arrays Endow Titanium Implants Excellent Osseointegration Performance and Nerve Formation Potential

Titanium based materials have been widely applied in bone-tissue engineering. However, inefficient bone repair remains to be solved due to the lack of neural network reconstruction at the bone-implant interface. Herein, we propose a functional surface modification approach to promote neurogenesis. Using an electrochemical technique and a hydrothermal approach, a potassium titanate nanorod-decorated titanium oxide (K2Ti6O13-TiO2) nanotube array is constructed on the surface of titanium implants. The K2Ti6O13-TiO2 hybrid nanotube array on titanium implants can enhance the osteogenic differentiation of mesenchymal stem cells due to the special nanostructures of titanium oxide nanorods. Meanwhile, the release of potassium ions is able to accelerate the neural differentiation of neural stem cells. This study provides a new approach to promote neuralization on the surface of implants, which is promising for future applications in constructing a fully functional interface in bone repair.
Gastrointestinal Stability and Cytotoxicity of Bacteriocins From Gram-Positive and Gram-Negative Bacteria: A Comparative in vitro Study

Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using in vitro models. In addition cytotoxicity and hemolytic activity of these bacteriocins were investigated on human epithelial colorectal adenocarcinoma cells (Caco-2) and rat erythrocytes, respectively. Pediocin PA-1, bactofencin A, and nisin were observed to lose their stability while passing through the gastrointestinal tract, while microcin J25 is only partially degraded. Besides, selected bacteriocins were not toxic to Caco-2 cells, and integrity of cell membrane was observed to remain unaffected in presence of these bacteriocins at concentrations up to 400 μg/mL. In hemolysis study, pediocin PA-1, bactofencin A, and nisin were observed to lyse rat erythrocytes at concentrations higher than 50 μg/mL, while microcin J25 showed no effect on these cells. According to data indicating gastrointestinal degradation and the absence of toxicity of pediocin PA-1, bactofencin A, and microcin J25 they could potentially be used in food or clinical applications.
Improving Robotic Hand Prosthesis Control With Eye Tracking and Computer Vision: A Multimodal Approach Based on the Visuomotor Behavior of Grasping

The complexity and dexterity of the human hand make the development of natural and robust control of hand prostheses challenging. Although a large number of control approaches were developed and investigated in the last decades, limited robustness in real-life conditions often prevented their application in clinical settings and in commercial products. In this paper, we investigate a multimodal approach that exploits the use of eye-hand coordination to improve the control of myoelectric hand prostheses. The analyzed data are from the publicly available MeganePro Dataset 1, that includes multimodal data from transradial amputees and able-bodied subjects while grasping numerous household objects with ten grasp types. A continuous grasp-type classification based on surface electromyography served as both intent detector and classifier. At the same time, the information provided by eye-hand coordination parameters, gaze data and object recognition in first-person videos allowed to identify the object a person aims to grasp. The results show that the inclusion of visual information significantly increases the average offline classification accuracy by up to 15.61 ± 4.22% for the transradial amputees and of up to 7.37 ± 3.52% for the able-bodied subjects, allowing trans-radial amputees to reach average classification accuracy comparable to intact subjects and suggesting that the robustness of hand prosthesis control based on grasp-type recognition can be significantly improved with the inclusion of visual information extracted by leveraging natural eye-hand coordination behavior and without placing additional cognitive burden on the user.
Expression Profile Analysis to Identify Circular RNA Expression Signatures in the Prolificacy Trait of Yunshang Black Goat Pituitary in the Estrus Cycle

The pituitary gland is an important organ. It is a complex area of the brain involved in endocrine function and reproductive regulation. However, the function of the pituitary in goat reproduction is still unclear. Herein, RNA sequencing was used to explore the expression patterns of circle RNAs (circRNAs) in the pituitary of Yunshang black goats during the various estrus phases. Then the host genes of the circRNAs were predicted, and a competing endogenous RNA (ceRNA) network was constructed. The results showed a total of 6,705 circRNAs in the pituitary of Yunshang black goats, among which 388 differentially expressed (DE) circRNAs (214 were upregulated, while 174 were downregulated) were identified between high- and low-yield Yunshang black goats in the follicular phase (HF vs. LF); moreover, 361 DE circRNAs (136 were upregulated, while 225 were downregulated) were identified between high- and low-yield Yunshang black goats in the luteal phase (HL vs. LL). There were 65 DE circRNAs targeting 40 miRNAs in the HF vs. LF comparison and 46 DE circRNAs targeting 31 miRNAs in the HL vs. LL comparison. We identified chi_circ_0030920, chi_circ_0043017, chi_circ_0008353, chi_circ_0041580, and chi_circ_0016478 as the key circRNAs through functional enrichment analysis. The ceRNA network analysis showed that chi_circ_0031209 and chi_circ_0019448 might play an important role in reproduction by influencing the expression of prolactin receptor (PRLR) in high- and low-yielding goats during the luteal phase, whereas chi_circ_0014542 regulates the expression of WNT5A during the follicular phase. Our study provided the overall expression profiles of circRNAs in the goat pituitary during the estrus phase, which provides new insight into the mechanism of high-yield goats, which can be helpful to guide goat breeding.
Btn2a2 Regulates ILC2–T Cell Cross Talk in Type 2 Immune Responses

Innate lymphoid cells (ILC) not only are responsible for shaping the innate immune response but also actively modulate T cell responses. However, the molecular processes regulating ILC-T cell interaction are not yet completely understood. The protein butyrophilin 2a2 (Btn2a2), a co-stimulatory molecule first identified on antigen-presenting cells, has a pivotal role in the maintenance of T cell homeostasis, but the main effector cell and the respective ligands remain elusive. We analyzed the role of Btn2a2 in the ILC-T cell cross talk. We found that the expression of Btn2a2 is upregulated in ILC2 following stimulation with IL-33/IL-25/TSLP. In vitro and in vivo experiments indicated that lack of Btn2a2 expression on ILC2 resulted in elevated T cell responses. We observed an enhanced proliferation of T cells as well as increased secretion of the type 2 cytokines IL-4/IL-5/IL-13 following cocultures with Btn2a2-deficient ILC2. In vivo transfer experiments confirmed the regulatory role of Btn2a2 on ILC2 as Btn2a2-deficient ILC2 induced stronger T cell responses and prevented chronic helminth infections. Taken together, we identified Btn2a2 as a significant player in the regulation of ILC2–T cell interactions.