Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylobacterium sp. 2A Is a Plant Growth-Promoting Rhizobacteria That Has the Potential to Improve Potato Crop Yield Under Adverse Conditions

A Gram-negative pink-pigmented bacillus (named 2A) was isolated from Solanum tuberosum L. cv. Desirée plants that were strikingly more developed, presented increased root hair density, and higher biomass than other potato lines of the same age. The 16S ribosomal DNA sequence, used for comparative gene sequence analysis, indicated that strain 2A belongs to the genus Methylobacterium. Nucleotide identity between Methylobacterium sp. 2A sequenced genome and the rest of the species that belong to the genus suggested that this species has not been described so far. In vitro, potato plants inoculated with Methylobacterium sp. 2A had a better performance when grown under 50 mM NaCl or when infected with Phytophthora infestans. We inoculated Methylobacterium sp. 2A in Arabidopsis thaliana roots and exposed these plants to salt stress (75 mM NaCl). Methylobacterium sp. 2A-inoculated plants, grown in control or salt stress conditions, displayed a higher density of lateral roots (p < 0.05) compared to noninoculated plants. Moreover, under salt stress, they presented a higher number of leaves and larger rosette diameter. In dual confrontation assays, Methylobacterium sp. 2A displayed biocontrol activity against P. infestans, Botrytis cinerea, and Fusarium graminearum, but not against Rhizoctonia solani, and Pythium dissotocum. In addition, we observed that Methylobacterium sp. 2A diminished the size of necrotic lesions and reduced chlorosis when greenhouse potato plants were infected with P. infestans. Methylobacterium sp. 2A produces indole acetic acid, solubilizes mineral phosphate and is able to grow in a N2 free medium. Whole-genome sequencing revealed metabolic pathways associated with its plant growth promoter capacity. Our results suggest that Methylobacterium sp. 2A is a plant growth-promoting rhizobacteria (PGPR) that can alleviate salt stress, and restricts P. infestans infection in potato plants, emerging as a potential strategy to improve crop management.
Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused by autoantibodies targeting neuromuscular junction proteins. In the majority of patients (~85%) antibodies against the muscle acetylcholine receptor (AChR) are detected, while in 6% antibodies against the muscle-specific kinase (MuSK) are detected. In ~10% of MG patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG), making the improvement of methods for the detection of known autoantibodies or the discovery of novel antigenic targets imperative. Over the past years, using cell-based assays or improved highly sensitive immunoprecipitation assays, it has been possible to detect autoantibodies in previously SN-MG patients, including the identification of the low-density lipoprotein receptor-related protein 4 (LRP4) as a third MG autoantigen, as well as AChR and MuSK antibodies undetectable by conventional methods. Furthermore, antibodies against other extracellular or intracellular targets, such as titin, the ryanodine receptor, agrin, collagen Q, Kv1.4 potassium channels and cortactin have been found in some MG patients, which can be useful biomarkers. In addition to the improvement of diagnosis, the identification of the patients' autoantibody specificity is important for their stratification into respective subgroups, which can differ in terms of clinical manifestations, prognosis and most importantly their response to therapies. The knowledge of the autoantibody profile of MG patients would allow for a therapeutic strategy tailored to their MG subgroup. This is becoming especially relevant as there is increasing progress toward the development of antigen-specific therapies, targeting only the specific autoantibodies or immune cells involved in the autoimmune response, such as antigen-specific immunoadsorption, which have shown promising results. We will herein review the advances made by us and others toward development of more sensitive detection methods and the identification of new antibody targets in MG, and discuss their significance in MG diagnosis and therapy. Overall, the development of novel autoantibody assays is aiding in the more accurate diagnosis and classification of MG patients, supporting the development of advanced therapeutics and ultimately the improvement of disease management and patient quality of life.
The Secretome Derived From Mesenchymal Stromal Cells Cultured in a Xeno-Free Medium Promotes Human Cartilage Recovery in vitro

Osteoarthritis (OA) is a disabling joint disorder causing articular cartilage degeneration. Currently, the treatments are mainly aimed to pain and symptoms relief, rather than disease amelioration. Human bone marrow stromal cells (hBMSCs) have emerged as a promising paracrine mechanism-based tool for OA treatment. Here, we investigate the therapeutic potential of conditioned media (CM) and extracellular vesicles (EVs) isolated from hBMSC and grown in a xeno-free culture system (XFS) compared to the conventional fetal bovine serum-culture system (FBS) in an in vitro model of OA. First, we observed that XFS promoted growth and viability of hBMSCs compared to FBS-containing medium while preserving their typical phenotype. The biological effects of the CM derived from hBMSC cultivated in XFS- and FBS-based medium were tested on IL-1α treated human chondrocytes, to mimic the OA enviroment. Treatment with CM derived from XFS-cultured hBMSC inhibited IL-1α-induced expression of IL-6, IL-8, and COX-2 by hACs compared to FBS-based condition. Furthermore, we observed that hBMSCs grown in XFS produced a higher amount of EVs compared to FBS-culture. The hBMSC-EVs not only inhibit the adverse effects of IL-1α-induced inflammation, but play a significant in vitro chondroprotective effect. In conclusion, the XFS medium was found to be suitable for isolation and expansion of hBMSCs with increased safety profile and intended for ready-to-use clinical therapies.
Factors Influencing Professional Help-Seeking Behavior During First Episode Psychosis in Schizophrenia: An Exploratory Study on Caregivers’ Perspective

Schizophrenia is a severe mental illness that leads to significant productivity loss and is listed in the top 15 global burdens of disease. One important contributor to the high disease burden is duration of untreated psychosis (DUP) which can be shortened with promotion of professional help-seeking behavior. This study explored caregivers' perspective on factors influencing professional help-seeking behavior during first episode psychosis (FEP) in schizophrenia in Malaysia. The results of this study would inform the development of intervention strategies targeted at promoting professional help-seeking behavior in caregivers of individuals experiencing first episode psychosis (FEP). This is a thematic exploratory study which employed purposive sampling using focus group discussion (FGD). These interviews were audio recorded and transcribed verbatim. Basic thematic approach was used in analyzing the transcribed interviews. Two main themes identified were adequacy of knowledge and stigma. These two factors were found to co-influence each other. Stigma undermined the impact of knowledge on professional help-seeking; likewise, the reverse was also observed. Intervention strategies for promoting help-seeking behavior during FEP should simultaneously focus on improving knowledge about schizophrenia and reducing the stigma attached to it.
Beneficial Endophytic Bacterial Populations Associated With Medicinal Plant Thymus vulgaris Alleviate Salt Stress and Confer Resistance to Fusarium oxysporum

As a result of climate change, salinity has become a major abiotic stress that reduces plant growth and crop productivity worldwide. A variety of endophytic bacteria alleviate salt stress; however, their ecology and biotechnological potential has not been fully realized. To address this gap, a collection of 117 endophytic bacteria were isolated from wild populations of the herb Thymus vulgaris in Sheikh Zuweid and Rafah of North Sinai Province, Egypt, and identified based on their 16S rRNA gene sequences. The endophytes were highly diverse, including 17 genera and 30 species. The number of bacterial species obtained from root tissues was higher (n = 18) compared to stem (n = 14) and leaf (n = 11) tissue. The endophytic bacteria exhibited several plant growth-promoting activities in vitro, including auxin synthesis, diazotrophy, phosphate solubilization, siderophore production, and production of lytic enzymes (i.e., chitinase, cellulase, protease, and lipase). Three endophytes representing Bacillus species associated with T. vulgaris such as EGY05, EGY21, and EGY25 were selected based on their ex-situ activities for growth chamber assays to test for their ability to promote the growth of tomato (Solanum lycopersicum L.) under various NaCl concentrations (50–200 mM). All three strains significantly (P < 0.05) promoted the growth of tomato plants under salt stress, compared to uninoculated controls. In addition, inoculated tomato plants by all tested strains decreased (P < 0.05) the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase). Six strains, representing Bacillus and Enterobacter species EGY01, EGY05, EGY16, EGY21, EGY25, and EGY31 were selected based on in vitro antagonistic activity to F. oxysporum for pot experiments under salt stress. All tested strains reduced the disease severity index (DSI) of tomato plants at all tested salt concentrations. Gas-chromatography/mass-spectrometry analysis of cell-free extracts of B. subtilis (EGY16) showed at least ten compounds were known to have antimicrobial activity, with the major peaks being benzene, 1,3-dimethyl-, p-xylene, dibutyl phthalate, bis (2-ethylhexyl) phthalate, and tetracosane. This study demonstrates that diverse endophytes grow in wild thyme populations and that some are able to alleviate salinity stress and inhibit F. oxysporum pathogenesis, making them promising candidates for biofertilizers and biocontrol agents.
Tailoring Biodegradability of Poly(Butylene Succinate)/Poly(Lactic Acid) Blends With a Deep Eutectic Solvent

Biodegradable polymers concern an important topic for innovation in materials, as they are supposed to contribute to the reduction in the amount of waste materials, which lead to microplastics with similar properties as conventional polymer materials. Poly(butylene succinate) and poly(lactic acid) blends are polymers with interesting properties offering possible alternatives to some conventional petrochemical-sourced polymers. Some of the physical properties of such blends can be tailored from the addition of small amounts of deep eutectic solvents (DESs) that can act as compatibilizers, i.e., interfacial agents between poly(butylene succinate) (PBS) and poly(lactic acid) (PLA). In our study, materials formulated with a DES having a coarse morphology according to the dispersed particle sizes display thermal and mechanical properties rather close to the non-compatibilized PBS/PLA blends but a higher ability to biodegrade. In comparison with PBS/PLA blend, biodegradation experiments show that PBS/PLA/DES blend exhibits higher weight losses and faster fragmentation under conventional conditions. A significant decrease in PLA melting temperature under composting conditions, i.e., at 58°C, is observed indicating that PLA phase is the component mainly concerned. As a conclusion, this work demonstrates that morphologies as well as the biodegradability process can be tailored by adding a small amount of a DES in such biosourced polymer blends. Indeed, designing polymer materials, for which degradation processes are targeted in the dispersed phase, i.e., in multiple locations of the material, can be an efficient route to “predegrade” phases in a polymer matrix to accelerate macroscopic biodegradation.
Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Pericytes are mural vascular cells found predominantly on the abluminal wall of capillaries, where they contribute to the maintenance of capillary structural integrity and vascular permeability. Generally quiescent cells in the adult, pericyte activation and proliferation occur during both physiological and pathological vascular and tissue remodeling. A considerable body of research indicates that pericytes possess attributes of a multipotent adult stem cell, as they are capable of self-renewal as well as commitment and differentiation into multiple lineages. However, pericytes also display phenotypic heterogeneity and recent studies indicate that lineage potential differs between pericyte subpopulations. While numerous microenvironmental cues and cell signaling pathways are known to regulate pericyte functions, the roles that metabolic pathways play in pericyte quiescence, self-renewal or differentiation have been given limited consideration to date. This review will summarize existing data regarding pericyte metabolism and will discuss the coupling of signal pathways to shifts in metabolic pathway preferences that ultimately regulate pericyte quiescence, self-renewal and trans-differentiation. The association between dysregulated metabolic processes and development of pericyte pathologies will be highlighted. Despite ongoing debate regarding pericyte classification and their functional capacity for trans-differentiation in vivo, pericytes are increasingly exploited as a cell therapy tool to promote tissue healing and regeneration. Ultimately, the efficacy of therapeutic approaches hinges on the capacity to effectively control/optimize the fate of the implanted pericytes. Thus, we will identify knowledge gaps that need to be addressed to more effectively harness the opportunity for therapeutic manipulation of pericytes to control pathological outcomes in tissue remodeling.
Monocytes and Macrophages as Protagonists in Vascular Complications of Diabetes

With the increasing prevalence of diabetes worldwide, vascular complications of diabetes are also on the rise. Diabetes results in an increased risk of macrovascular complications, with atherosclerotic cardiovascular disease (CVD) being the leading cause of death in adults with diabetes. The exact mechanisms for how diabetes promotes CVD risk are still unclear, although it is evident that monocytes and macrophages are key players in all stages of atherosclerosis both in the absence and presence of diabetes, and that phenotypes of these cells are altered by the diabetic environment. Evidence suggests that at least five pro-atherogenic mechanisms involving monocytes and macrophages contribute to the accelerated atherosclerotic lesion progression and hampered lesion regression associated with diabetes. These changes include (1) increased monocyte recruitment to lesions; (2) increased inflammatory activation; (3) altered macrophage lipid accumulation and metabolism; (4) increased macrophage cell death; and (5) reduced efferocytosis. Monocyte and macrophage phenotypes and mechanisms have been revealed mostly by different animal models of diabetes. The roles of specific changes in monocytes and macrophages in humans with diabetes remain largely unknown. There is an ongoing debate on whether the changes in monocytes and macrophages are caused by altered glucose levels, insulin deficiency or insulin resistance, lipid abnormalities, or combinations of these factors. Current research in humans and mouse models suggests that reduced clearance of triglyceride-rich lipoproteins and their remnants is one important mechanism whereby diabetes adversely affects macrophages and promotes atherosclerosis and CVD risk. Although monocytes and macrophages readily respond to the diabetic environment and can be seen as protagonists in diabetes-accelerated atherosclerosis, they are likely not instigators of the increased CVD risk.
Extracellular Vesicles and Chemotherapy Resistance in the AML Microenvironment

Extracellular vesicle (EV) trafficking provides for a constitutive mode of cell-cell communication within tissues and between organ systems. Different EV subtypes have been identified that transfer regulatory molecules between cells, influencing gene expression, and altering cellular phenotypes. Evidence from a range of studies suggests that EV trafficking enhances cell survival and resistance to chemotherapy in solid tumors. In acute myeloid leukemia (AML), EVs contribute to the dynamic crosstalk between AML cells, hematopoietic elements and stromal cells and promote adaptation of compartmental bone marrow (BM) function through transport of protein, RNA, and DNA. Careful analysis of leukemia cell EV content and phenotypic outcomes provide evidence that vesicles are implicated in transferring several known key mediators of chemoresistance, including miR-155, IL-8, and BMP-2. Here, we review the current understanding of how EVs exert their influence in the AML niche, and identify research opportunities to improve outcomes for relapsed or refractory AML patients.
Cell Tracking in Cancer Immunotherapy

The impressive development of cancer immunotherapy in the last few years originates from a more precise understanding of control mechanisms in the immune system leading to the discovery of new targets and new therapeutic tools. Since different stages of disease progression elicit different local and systemic inflammatory responses, the ability to longitudinally interrogate the migration and expansion of immune cells throughout the whole body will greatly facilitate disease characterization and guide selection of appropriate treatment regiments. While using radiolabeled white blood cells to detect inflammatory lesions has been a classical nuclear medicine technique for years, new non-invasive methods for monitoring the distribution and migration of biologically active cells in living organisms have emerged. They are designed to improve detection sensitivity and allow for a better preservation of cell activity and integrity. These methods include the monitoring of therapeutic cells but also of all cells related to a specific disease or therapeutic approach. Labeling of therapeutic cells for imaging may be performed in vitro, with some limitations on sensitivity and duration of observation. Alternatively, in vivo cell tracking may be performed by genetically engineering cells or mice so that may be revealed through imaging. In addition, SPECT or PET imaging based on monoclonal antibodies has been used to detect tumors in the human body for years. They may be used to detect and quantify the presence of specific cells within cancer lesions. These methods have been the object of several recent reviews that have concentrated on technical aspects, stressing the differences between direct and indirect labeling. They are briefly described here by distinguishing ex vivo (labeling cells with paramagnetic, radioactive, or fluorescent tracers) and in vivo (in vivo capture of injected radioactive, fluorescent or luminescent tracers, or by using labeled antibodies, ligands, or pre-targeted clickable substrates) imaging methods. This review focuses on cell tracking in specific therapeutic applications, namely cell therapy, and particularly CAR (Chimeric Antigen Receptor) T-cell therapy, which is a fast-growing research field with various therapeutic indications. The potential impact of imaging on the progress of these new therapeutic modalities is discussed.
Evaluation of EEG Headset Mounting for Brain-Computer Interface-Based Stroke Rehabilitation by Patients, Therapists, and Relatives

Brain-computer interfaces (BCIs) have successfully been used for motor recovery training in stroke patients. However, the setup of BCI systems is complex and may be divided into (1) mounting the headset and (2) calibration of the BCI. One of the major problems is mounting the headset for recording brain activity in a stroke rehabilitation context, and usability testing of this is limited. In this study, the aim was to compare the translational aspects of mounting five different commercially available headsets from a user perspective and investigate the design considerations associated with technology transfer to rehabilitation clinics and home use. No EEG signals were recorded, so the effectiveness of the systems have not been evaluated. Three out of five headsets covered the motor cortex which is needed to pick up movement intentions of attempted movements. The other two were as control and reference for potential design considerations. As primary stakeholders, nine stroke patients, eight therapists and two relatives participated; the stroke patients mounted the headsets themselves. The setup time was recorded, and participants filled in questionnaires related to comfort, aesthetics, setup complexity, overall satisfaction, and general design considerations. The patients had difficulties in mounting all headsets except for a headband with a dry electrode located on the forehead (control). The therapists and relatives were able to mount all headsets. The fastest headset to mount was the headband, and the most preferred headsets were the headband and a behind-ear headset (control). The most preferred headset that covered the motor cortex used water-based electrodes. The patients reported that it was important that they could mount the headset themselves for them to use it every day at home. These results have implications for design considerations for the development of BCI systems to be used in rehabilitation clinics and in the patient’s home.