Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 Landes Bioscience.The potential of mesenchymal stem cells (MSC) to differentiate into neural lineages has raised the possibility of autologous cell transplantation as a therapy for neurodegenerative diseases. We have identified a population of circulating human fetal mesenchymal stem cells (hfMSC) that are highly proliferative and can readily differentiate into mesodermal lineages such as bone, cartilage, fat and muscle. Here, we demonstrate for the first time that primary hfMSC can differentiate into cells with an oligodendrocyte phenotype both in vitro and in vivo. By exposing hfMSC to neuronal conditioned medium or by introducing the pro-oligodendrocyte gene, Olig-2, hfMSC adopted an oligodendrocyte-like morphology, expressed oligodendrocyte markers and appeared to mature appropriately in culture. Importantly we also demonstrate the differentiation of a clonal population of hfMSC into both mesodermal (bone) and ectodermal (oligodendrocyte) lineages. In the developing murine brain transplanted hfMSC integrated into the parenchyma but oligodendrocyte differentiation of these naïve hfMSC was very low. However, the proportion of cells expressing oligodendrocyte markers increased significantly (from 0.2% to 4%) by pre-exposing the cells to differentiation medium in vitro prior to transplantation. Importantly, the process of in vivo differentiation occurred without cell fusion. These findings suggest that hfMSC may provide a potential source of oligodendrocytes for study and potential therapy

Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK

BACKGROUND: The burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or the extent to which they relate to disease severity. METHODS: We performed a cross-sectional analysis using IID cases identified from a large population-based survey, to explore the association between socioeconomic status (SES) and symptom severity and sickness absence; and to assess the role of symptom severity on the relationship between SES and absence. Regression modelling was used to investigate these associations, whilst controlling for potential confounders such as age, sex and ethnicity. RESULTS: Among 1164 cases, those of lower SES versus high had twice the odds of experiencing severe symptoms (OR 2.2, 95%CI;1.66-2.87). Lower SES was associated with higher odds of sickness absence (OR 1.8, 95%CI;1.26-2.69), however this association was attenuated after adjusting for symptom severity (OR 1.4, 95%CI;0.92-2.07). CONCLUSIONS: In a large sample of IID cases, those of low SES versus high were more likely to report severe symptoms, and sickness absence; with greater severity largely explaining the higher absence. Public health interventions are needed to address the unequal consequences of IID identified

Socioeconomic status and infectious intestinal disease in the community: a longitudinal study (IID2 study).

Infectious intestinal diseases (IID) are common, affecting around 25% of people in UK each year at an estimated annual cost to the economy, individuals and the NHS of £1.5 billion. While there is evidence of higher IID hospital admissions in more disadvantaged groups, the association between socioeconomic status (SES) and risk of IID remains unclear. This study aims to investigate the relationship between SES and IID in a large community cohort.Longitudinal analysis of a prospective community cohort in the UK following 6836 participants of all ages was undertaken. Hazard ratios for IID by SES were estimated using Cox proportional hazard, adjusting for follow-up time and potential confounding factors.In the fully adjusted analysis, hazard ratio of IID was significantly lower among routine/manual occupations compared with managerial/professional occupations (HR 0.74, 95% CI 0.61-0.90).In this large community cohort, lower SES was associated with lower IID risk. This may be partially explained by the low response rate which varied by SES. However, it may be related to differences in exposure or recognition of IID symptoms by SES. Higher hospital admissions associated with lower SES observed in some studies could relate to more severe consequences, rather than increased infection risk

Do cognitive training strategies improve motor and positive psychological skills development in soccer players? Insights from a systematic review

Soccer players are required to have well-developed physical, technical and cognitive abilities. The present systematic review, adhering to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, examined the effects of cognitive training strategies on motor and positive psychological skills development in soccer performance and identified the potential moderators of the “cognitive training-soccer performance” relationship. Thirteen databases were systematically searched using keywords related to psychological or cognitive training in soccer players. The review is based on 18 studies, employing 584 soccer players aged 7-39 years. Cognitive strategies, particularly imagery, appear to improve sports performance in soccer players. Regarding imagery, the combination of two different types of cognitive imagery training (i.e., cognitive general and cognitive specific) have a positive influence on soccer performance during training, whereas motivational imagery (i.e., motivational general-arousal, motivational general-mastery, and motivational specific) enhance competition performance. Younger soccer players employ cognitive general and cognitive specific imagery techniques to a greater extent than older soccer players. Combined cognitive training strategies were more beneficial than a single cognitive strategy relative to motor skills enhancement in elite (particularly midfielders) and amateur (i.e., when practicing complex and specific soccer skills in precompetitive period) soccer players. In conclusion, it appears that there are differences in cognitive/psychological training interventions, and their efficacy, according to whether they are directed towards training or competition, and the age, standard and playing position of the players

Climate change and the aquatic ecosystems of the Rwenzori Mountains, Uganda

The Rwenzori Mountains are home to one of the last remaining tropical icefields outside of the Andes. Over the last century, equatorial icefields of the East African highlands have been steadily shrinking but the precise climate tropical alpine glaciers remain unclear. More than a decade had passed since the last detailed measurements of glacial cover were made in the Rwenzori Mountains. Recent evidence from Kilimanjaro suggests that its icecap will disappear entirely by the year 2020(1). The Rwenzori glaciers contribute meltwater flows to aquatic ecosystems of the Rwenzori Mountains National Park, a Word Heritage Site featuring spectacular, rare Afroalpine flora and fauna, and are headwaters of the River Nile. With the overall aim of assessing the impact of recent climate change on alpine aquatic ecosystems of the Rwenzori Mountains, a collaborative, international research team led by the University College London (United Kingdom) and Makerere University (Uganda), and involving the Institut für Geographie from the University of Innsbruck (Austria) and Water Resources Management Department (Uganda) was assembled in order to pursue three primary scientific objectives: • to assess the magnitude of current glacial recession; • to assess the impact of glacial recession on alpine riverflow; and • to assess recent environmental change from observational datasets and available, environmental archives stored in lake sediment and glacial ice

Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

Neurospora from natural populations: Population genomics insights into the Life history of a model microbial Eukaryote

The ascomycete filamentous fungus Neurospora crassa played a historic role in experimental biology and became a model system for genetic research. Stimulated by a systematic effort to collect wild strains initiated by Stanford geneticist David Perkins, the genus Neurospora has also become a basic model for the study of evolutionary processes, speciation, and population biology. In this chapter, we will first trace the history that brought Neurospora into the era of population genomics. We will then cover the major contributions of population genomic investigations using Neurospora to our understanding of microbial biogeography and speciation, and review recent work using population genomics and genome-wide association mapping that illustrates the unique potential of Neurospora as a model for identifying the genetic basis of (potentially adaptive) phenotypes in filamentous fungi. The advent of population genomics has contributed to firmly establish Neurospora as a complete model system and we hope our review will entice biologists to include Neurospora in their research

Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis

Objective Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical outcomes. Methods An integrated analysis was conducted by pooling data from 3 completed phase III trials comparing placebo with baricitinib treatment (RA‐BEAM, RA‐BUILD, and RA‐BEACON) and 1 ongoing long‐term extension study (RA‐BEYOND) in patients with active RA (n = 2,186). Results Baricitinib treatment was associated with an early transient increase in total lymphocyte count at week 4, which returned to baseline by week 12. Transient changes within normal reference ranges in T cells and subsets were observed with baricitinib treatment, up to week 104. B cells and relevant subpopulations increased after 4 weeks of baricitinib treatment, with no further increases noted through 104 weeks of treatment. Natural killer (NK) cells temporarily increased after 4 weeks of baricitinib treatment, before decreasing below baseline levels and then stabilizing over time. With baricitinib treatment, few correlations were observed between changes in lymphocyte subsets and clinical end points, and most correlations were also observed within the placebo group. A modest potential association between low NK cell numbers and treatment‐emergent infections was observed in the baricitinib 4 mg/day treatment group, but not for serious infections or herpes zoster. Conclusion Overall, these findings demonstrate that changes in lymphocyte subsets were largely within normal reference ranges across the baricitinib phase III RA clinical program and were not associated with increased risk of serious infections

Bioenergetic model sensitivity to diet diversity across space, time and ontogeny

Consumption is the primary trophic interaction in ecosystems and its accurate estimation is required for reliable ecosystem modeling. When estimating consumption, species' diets are commonly assumed to be the average of those that occur among habitats, seasons, and life stages which introduces uncertainty and error into consumption rate estimates. We present a case study of a teleost (Yellowfin Bream Acanthopagrus australis) that quantifies the potential error in consumption (in mass) and growth rate estimates when using diet data from different regions and times and ignoring ontogenetic variability. Ontogenetic diet trends were examined through gut content analysis (n = 1,130 fish) and incorporated into a bioenergetic model (the "primary " model) that included diet variability (n = 144 prey sources) and ontogenetic changes in metabolism (1-7 year) to estimate lifetime consumption. We quantified error by building nine model scenarios that each incorporated different spatiotemporal diet data of four published studies. The model scenarios produced individual lifetime consumption estimates that were between 25% lower and 15% higher than the primary model (maximum difference was 53%, range 11.7-17.8 kg). When consumption (in mass) was held constant, differences in diet quality among models caused a several-fold range in growth rate (0.04-1.07 g day(-1)). Our findings showcase the large uncertainty in consumption rate estimates due to diet diversity, and illustrate that caution is required when considering bioenergetic results among locations, times, and ontogeny

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/μl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients