B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte glycoprotein (MOG) and compare the response with a standard model foreign antigen. Both antigens generate productive primary responses, as evidenced by GC development, circulating antigen-specific antibodies, and differentiation of memory B cells. However, in the MOG response, the status of the cognate T cell partner drives preferential B cell differentiation to a memory phenotype at the expense of GC maintenance, resulting in a truncated GC. Reduced plasma cell differentiation is largely independent of T cell influence. Interestingly, memory-phenotype B cells formed in the MOG GC are not long lived, resulting in a failure of the B cell response to secondary challenge.

Antibody affinity maturation, which is an antigen-based selection process for B cells, occurs in germinal centers (GCs). GCB cells must efficiently recognize, acquire, and present antigens from follicular dendritic cells (FDCs) to receive positive selection signals from T helper cells. Previous studies showed that GCB cells undergo adhesive interactions with FDCs, but the regulatory mechanisms underlying the cell adhesions and their functional relevance remain unclear. Here, we identified H3K36me2 methyltransferase Nsd2 as a critical regulator of GCB cell-FDC adhesion. Nsd2 deletion modestly reduced GC responses but strongly impaired B cell affinity maturation. Mechanistically, Nsd2 directly regulated expression of multiple actin polymerization-related genes in GCB cells. Nsd2 loss reduced B cell adhesion to FDC-expressed adhesion molecules, thus affecting both B cell receptor (BCR) signaling and antigen acquisition. Overall, Nsd2 coordinates GCB positive selection by enhancing both BCR signaling and T cell help.

Single-nucleotide polymorphisms in ETS1 are associated with systemic lupus erythematosus (SLE). Ets1-/- mice develop SLE-like symptoms, suggesting that dysregulation of this transcription factor is important to the onset or progression of SLE. We used conditional deletion approaches to examine the impact of Ets1 expression in different immune cell types. Ets1 deletion on CD4+ T cells, but not B cells or dendritic cells, resulted in the SLE autoimmunity, and this was associated with the spontaneous expansion of T follicular helper type 2 (Tfh2) cells. Ets1-/- Tfh2 cells exhibited increased expression of GATA-3 and interleukin-4 (IL-4), which induced IgE isotype switching in B cells. Neutralization of IL-4 reduced Tfh2 cell frequencies and ameliorated disease parameters. Mechanistically, Ets1 suppressed signature Tfh and Th2 cell genes, including Cxcr5, Bcl6, and Il4ra, thus curbing the terminal Tfh2 cell differentiation process. Tfh2 cell frequencies in SLE patients correlated with disease parameters, providing evidence for the relevance of these findings to human disease.

Nanoparticles can be used in a large variety of applications, including magnetic sensing, biological, superconductivity, tissue engineering, and other fields. In this study, we explore the fabrication of gas phase silver nanoparticles using a sputtering evaporation source. This setup composed of a dual magnetron cluster source holds several advantages over other techniques. The system has independent control over the cluster concentration and a wide range of cluster size and materials that can be used for the clusters and for the matrix where it can be embedded. Characterization of these silver nanoparticles was done using transmission electron microscopy (TEM). We obtain a lateral width of 10.6 nm with a dispersion of 0.24 nm. With atomic force microscopy (AFM) a Gaussian fit of this distribution yields and average height of 6.3 nm with a standard deviation of 1.4 nm. We confirm that the deposited silver nanoparticles have a homogenous area distribution, that they have a defined shape and size distribution, and that they are single standing nanoparticles. Given that the scientific literature is not precise regarding the toxic concentration of the nanoparticles, devices such as ours can help clarify these questions. In order to explore further biological applications, we have done preliminary experiments of cell spreading (myoblast adhesion), obtaining interesting morphological changes correlated with the silver concentration on the surface. With a deposited silver concentration ranging from 100⁻620 ng/cm², the cells showed morphological changes in a short time of 2 h. We conclude that this high precision nanoparticle fabrication technique is adequate for further biological research.

Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation. The present study is aimed at determining the effects of ZNF521 on the osteoblastic differentiation of hADSCs to clarify whether it can influence their osteogenic commitment. The enforced expression or silencing of ZNF521 in hADSCs was achieved by lentiviral vector transduction. Cells were cultured in a commercial osteogenic medium for up to 20 days. The ZNF521 enforced expression significantly reduced osteoblast development as assessed by the morphological and molecular criteria, resulting in reduced levels of collagen I, alkaline phosphatase, osterix, osteopontin, and calcium deposits. Conversely, ZNF521 silencing, in response to osteoblastic stimuli, induced a significant increase in early molecular markers of osteogenesis and, at later stages, a remarkable enhancement of matrix mineralization. Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in hADSCs and suggest that its expression may contribute to maintaining the immature properties of hADSCs.

We found previously that white adipose tissue (WAT) hyperplasia in obese mice was limited by dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA). Here we aimed to characterize the underlying mechanism. C57BL/6N mice were fed a high-fat diet supplemented or not with omega-3 PUFA for one week or eight weeks; mice fed a standard chow diet were also used. In epididymal WAT (eWAT), DNA content was quantified, immunohistochemical analysis was used to reveal the size of adipocytes and macrophage content, and lipidomic analysis and a gene expression screen were performed to assess inflammatory status. The stromal-vascular fraction of eWAT, which contained most of the eWAT cells, except for adipocytes, was characterized using flow cytometry. Omega-3 PUFA supplementation limited the high-fat diet-induced increase in eWAT weight, cell number (DNA content), inflammation, and adipocyte growth. eWAT hyperplasia was compromised due to the limited increase in the number of preadipocytes and a decrease in the number of endothelial cells. The number of leukocytes and macrophages was unaffected, but a shift in macrophage polarization towards a less inflammatory phenotype was observed. Our results document that the counteraction of eWAT hyperplasia by omega-3 PUFA in dietary-obese mice reflects an effect on the number of adipose lineage and endothelial cells.

The study applied ¹H NMR-based plasma metabolomics to identify candidate biomarkers of aflatoxin B1 (AFB₁) ingestion in dairy cows fed no sequestering agents and evaluate the effect of supplementing clay and/or a Saccharomyces cerevisiae fermentation product (SCFP) on such biomarkers. Eight lactating cows were randomly assigned to 1 of 4 treatments in a balanced 4 × 4 Latin square design with 2 squares. Treatments were: control, toxin (T; 1725 µg AFB₁/head/day), T with clay (CL; 200 g/head/day), and CL with SCFP (CL + SCFP; 35 g of SCFP/head/day). Cows in T, CL, and CL + SCFP were dosed with AFB₁ from d 26 to 30. The sequestering agents were top-dressed from d 1 to 33. On d 30 of each period, 15 mL of blood was taken from the coccygeal vessels and plasma samples were prepared by centrifugation. Compared to the control, T decreased plasma concentrations of alanine, acetic acid, leucine, arginine and valine. In contrast, T increased plasma ethanol concentration 3.56-fold compared to control. Treatment with CL tended to reduce sarcosine concentration, whereas treatment with CL + SCFP increased concentrations of mannose and 12 amino acids. Based on size of the area under the curve (AUC) of receiver operating characteristic and fold change (FC) analyses, ethanol was the most significantly altered metabolite in T (AUC = 0.88; FC = 3.56); hence, it was chosen as the candidate biomarker of aflatoxin ingestion in dairy cows fed no sequestering agent.

Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that significantly contributes to morbidity and mortality. Macrophage migration inhibitory factor (MIF) is a critical factor in vascular remodeling of the pulmonary circulation.

Access to assistive products (AP) is an under-researched public health issue. Using an adaptation of a draft World Health Organization tool-the 'Assistive Technology Assessment-Needs (ATA-N)' for measuring unmet needs and use of AP, we aimed to understand characteristics of AP users, self-reported needs and unmet needs for AP, and current access patterns in Bangladesh. The ATA-N was incorporated in a Rapid Assessment of Disability (RAD), a population-based survey to estimate prevalence and correlates of disability. In each of two unions of Kurigram and Narsingdi districts, 60 clusters of 50 people each aged two years and older were selected using a two-staged cluster random sampling process, of whom, 4250 (59% Female; 41% Male) were adults, including 333 using AP. We estimate 7.1% of the studied population used any AP. AP use is positively associated with age and self-reported functional difficulty. The proportion of people using AP is higher for mobility than for sensory and cognitive difficulties. Of all people with any functional difficulty, 71% self-reported an unmet need for AP. Most products were home or self-made, at low cost, but provided benefits. Needs and unmet needs for AP are high, especially for people with greater functional difficulties. Assessing unmet needs for AP revealed important barriers to scale that can inform policy and practice.

Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 48 h to induce ER stress in the liver and examined the metabolic pathway that synthesizes the endogenous antioxidant, glutathione (GSH). Tunicamycin (TM) treatment significantly increased mRNA levels of CHOP and GRP78, and induced lipid accumulation in the liver. Lipid peroxidation in the liver tissue also increased from TM treatment (CON vs. TM; 3.0 ± 1.8 vs. 11.1 ± 0.8 nmol MDA/g liver, p < 0.001), which reflects an imbalance between the generation of reactive substances and antioxidant capacity. To examine the involvement of GSH synthetic pathway, we determined the metabolomic changes of sulfur amino acids in the liver. TM significantly decreased hepatic S-adenosylmethionine concentration in the methionine cycle. The levels of cysteine in the liver were increased, while taurine concentration was maintained and GSH levels profoundly decreased (CON vs. TM; 8.7 ± 1.5 vs. 5.4 ± 0.9 µmol GSH/g liver, p < 0.001). These results suggest that abnormal cysteine metabolism by TM treatment resulted in a decrease in GSH, followed by an increase in oxidative stress in the liver. In HepG2 cells, decreased GSH levels were examined by TM treatment in a dose dependent manner. Furthermore, pretreatment with TM in HepG2 cells potentiated oxidative cell death, by exacerbating the effects of tert-butyl hydroperoxide. In conclusion, TM-induced ER stress was accompanied by oxidative stress by reducing the GSH synthesis, which made the liver more susceptible to oxidative stress.

Liriodendron is a genus of Magnoliaceae, which consists of two relict species, Liriodendron chinense and L. tulipifera. Although the morphologies are highly similar, the two species exhibit different adaptive capacity. Dehydrins (DHNs) are abiotic stresses resistant proteins in planta, which are associated with adaptive evolution. To better understand the evolution divergence between L. chinense and L. tulipifera and how DHN genes are associated with adaptation evolution, we firstly investigated the DNA polymorphisms of the LcDHN-like gene in 21 L. chinense and 6 L. tulipifera populations.

To introduce and manage a Pharmaceutical care programs in geriatric care institutions presents difficulties such as reduced pharmacy service staff, complexity of the patients or lack of integration of the pharmacist in the health care team. This work describes the evolution of the implementations of a program of pharmaceutical care centered in drug related problems (DRP) in a group of geriatric institutions of different levels of complexity.

Most patients with antihypertensive medication do not achieve their blood pressure (BP) target. The most important factor behind this failure is poor medication adherence. However, non-adherence to therapy does not concern only patients. Clinicians also tend to lack adherence to hypertension guidelines, overestimate BP control and be satisfied with inadequate BP control. The aim of this non-blinded, cluster-randomised, controlled study was to investigate if using a checklist would improve the quality of care in the initiation of new antihypertensive medication and help reduce non-adherence.

Bovine papillomavirus (BPV) belongs to the Papillomaviridae family and infects epithelial cells of bovines and closely related animals, causing hyperproliferative lesions known as warts or papillomas, which may regress or progress to form benign or malignant tumors. The virus enters the host cell and interacts with it by altering the regulation of genes that are responsible for controlling the cell cycle, thus triggering lesion formation. It is not yet known which host genes are regulated by viral infection. Therefore, the objective of this study was to make use of next-generation RNA sequencing methods to identify differentially expressed genes associated with BPV infection, which might elucidate possible marker genes that could be used to control the disease.

To describe pre-hospital, emergency department and acute care assessment and management practices of senior clinicians for patients with acute traumatic spinal cord injury (TSCI) across Australia; and to describe clinical practice variation.

Breast cancer is the most common malignancy in women affecting one out of eight females throughout their lives. Autotaxin (ATX) is upregulated in breast cancer which results in increased lysophosphatidic acid (LPA) formation within the tumor. This study's aim was to identify the role of different mammary cell populations within the ATX-LPA axis.

Duchenne Muscular Dystrophy (DMD) is a severe, life-limiting and incurable condition. However, studies estimating quality of life and those measuring actual quality of life in people living with DMD vary considerably. This discrepancy indicates potential difficulties with assessing quality of life using common generic quality of life instruments in this rare and unique population. This study sought to document the range of themes relevant to quality of life for people with DMD by examining the published literature and additionally to investigate the themes that are relevant to quality of life for carers and the wider family. Eligible studies for the review were primary studies of any study design that reported outcomes or themes relevant to quality of life for either people with DMD, their families, or both. A review of studies identified from searching medical bibliographic sources between 2010 and 2016 found 45 relevant published studies. A thematic framework is proposed to categorise the themes identified into: i. physical; ii. psychological; iii. Social; iv. well-being domains. A final "other" domain was included to encompass themes identified from the literature that are not covered by commonly used quality of life instruments. The rich variety of themes identified from the review highlights that DMD has a complex quality of life profile which is not currently captured by standard quality of life tools that are commonly employed in the healthcare setting. The findings also highlight that the resulting impact on the quality of life of carers and wider family of people with DMD requires consideration.

Rapid transmission and high mortality of Ebola virus disease (EVD) highlight a urgent need of large scale, convenient and effective measure for Ebola virus screening. Application of monoclonal antibodies (mAbs) are crucial for establishment of an enzyme-linked immunosorbent assay (ELISA) with high sensitivity and specificity.

Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products for cellular therapies. Since the healing of bone fractures depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist.

Post-traumatic Stress Disorder (PTSD) is a common sequelae of severe combat-related emotional trauma that is often associated with significantly reduced quality of life in afflicted veterans. To date, no published study has examined the effect of an active, music-instruction intervention as a complementary strategy to improve the psychological well-being of veterans with PTSD. The purpose of this study was to examine the feasibility and potential effectiveness of an active, music-instruction intervention in improving psychological health and social functioning among Veterans suffering from moderate to severe PTSD.