Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis.

Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease

Algal Growth Potentials and Heavy Metal Concentrations of the Primary Streams to Upper Beaver Lake

Meyer and Green (1984) demonstrated the probable inhibition of algal growth potential by heavy metals in upper Beaver Lake. Upper Beaver Lake receives water from three tributaries. One contains a small reservoir and the combined streams receive sewage input. Collections were made approximately monthly at eight sites for the Algal Assay Bottle Test (AABT) and heavy metal analysis. In general, AABT results indicated that the collections above the sewage lnput were phosphorus limited while those below were nitrogen or combined nitrogen and phosphorus limited. Growth inhibition occurred during summer and early fall at various sites with greater inhibition at the confluence of the streams. No inhibitions occurred, at the site below the sewage input. Heavy metal concentrations had an overall tendency to increase downstream. Values within the small reservoir were 50-100% higher than in the feeder stream. Highest values of Pb were observed below the reservoir. SO4 ,Cl, Mg, Ca, Na and K had high values during low flow in August-ctober. The low values were independent of high flow. Pb followed an independent pattern. Storm event results showed that the Ca maximum was before the hydrographic peak while Fe, Mn, Pb, In, Co, Ni, Cu and Cd attained their maximum just after the peak. Maximum values were 4-10 times background values. Mn, Pb and Fe exceeded EPA recommended standards for drinking water

Discharge destination from an acute care for the elderly (ACE) unit

Older adults age 65 and over account for a disproportional number of hospital stays and discharges compared to other age groups. The objective of this paper is to describe placement and characteristics of older patients discharged from an acute care for the elderly (ACE) unit. The study sample consists of 1,351 men and women aged 65 years or older that were discharged from the ACE Unit during a 12-month period. The mean number of discharges per month was 109.2 ± 28.4. Most of the subjects were discharged home or home with home health 841, 62.3%. The oldest elderly and patients who had been admitted from long term care institutions or from skilled nursing facilities to the ACE unit were less likely to return to home

Electrical Power Grid Delivery Dynamic Analysis: Using Prime Mover Engines to Balance Dynamic Wind Turbine Output

This paper presents an investigation into integrated wind + combustion engine high penetration electrical generation systems. Renewable generation systems are now a reality of electrical transmission. Unfortunately, many of these renewable energy supplies are stochastic and highly dynamic. Conversely, the existing national grid has been designed for steady state operation. The research team has developed an algorithm to investigate the feasibility and relative capability of a reciprocating internal combustion engine to directly integrate with wind generation in a tightly coupled Hybrid Energy System. Utilizing the Idaho National Laboratory developed Phoenix Model Integration Platform, the research team has coupled demand data with wind turbine generation data and the Aspen Custom Modeler reciprocating engine electrical generator model to investigate the capability of reciprocating engine electrical generation to balance stochastic renewable energy

Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: implications for B-cell selection

Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA still had significantly higher frequency of N-linked motifs compared to all studied mAbs including highly-mutated HIV broadly-neutralizing and malaria-associated mAbs. The Fab glycans of ACPA-mAbs were highly sialylated, contributed to altered charge, but did not influence antigen binding. The analysis revealed evidence of unusual B-cell selection pressure and SHM-mediated decreased in surface charge and isoelectric point in ACPA. It is still unknown how these distinct features of anti-citrulline immunity may have an impact on pathogenesis. However, it is evident that they offer selective advantages for ACPA+ B cells, possibly also through non-antigen driven mechanisms

Using Mixed-Methods to Measure the Perception of Community Capacity In an Academic-Community Partnership for a Walking Intervention

H.U.B. City Steps is a 5-year community-based participatory research walking intervention designed to help lower blood pressure in a majority African American population in southern Mississippi via community collaboration and capacity building, increased walking, culturally tailored health education sessions, and motivational interviewing. Building community capacity for physical activity is a key component of this intervention. Qualitative and quantitative methods have been used to assess how project stakeholders perceive the community capacity-building efforts of the project. This article illustrates the baseline results of this mixed methods approach from the perspective of three groups of stakeholders: project researchers and staff, community advisory board, and intervention walking coaches. Eight constructs were examined, including leadership, resources, external networking, visibility and recognition, personnel sustainability, ability and commitment to organize, communication with community members, and relationships with influential others. Quantitative results indicated significant differences among stakeholder groups for project leadership and personnel sustainability. Qualitative perspectives provided an opportunity to examine possible reasons for these differences. Overall findings provide direction related to improving intervention outcomes and sustainability

Identificat el receptor de la relaxació del còlon

Un grup d'investigadors del Departament de Biologia Cel·lular, Fisiologia e Immunologia i de l'Institut de Neurociències de la UAB han confirmat que el receptor P2Y1 és responsable de la relaxació del còlon. Una recerca prèviament realitzada a la UAB en mostres de colon humà, ha estat confirmada en aquest estudi amb un ratolí genèticament modificat que no té el receptor i per tant el colon no es relaxa. Futurs estudis permetran valorar la funció del receptor en diferents patologies.Un grupo de investigadores del Departamento de Biología Celular, Fisiología e Inmunología y del Instituto de Neurociencias de la UAB han confirmado que el receptor P2Y1 es responsable de la relajación del colon. Una investigación previamente realizada en la UAB en muestras de colon humano, ha sido confirmada en este estudio con ratón genéticamente modificado que no tiene el receptor y por tanto el colon del cual no se relaja. Futuros estudios permitirán valorar la función del receptor en diferentes patologías