Paving the way for adequate myelination: The contribution of galectin-3, transferrin and iron

AbstractConsidering the worldwide incidence of well characterized demyelinating disorders such as Multiple Sclerosis (MS) and the increasing number of pathologies recently found to involve hypomyelinating factors such as micronutrient deficits, elucidating the molecular basis of central nervous system (CNS) demyelination, remyelination and hypomyelination becomes essential to the development of future neuroregenerative therapies. In this context, this review discusses novel findings on the contribution of galectin-3 (Gal-3), transferrin (Tf) and iron to the processes of myelination and remyelination and their potentially positive regulation of oligodendroglial precursor cell (OPC) differentiation. Studies were conducted in cuprizone (CPZ)-induced demyelination and iron deficiency (ID)-induced hypomyelination, and the participation of glial and neural stem cells (NSC) in the remyelination process was evaluated by means of both in vivo and in vitro assays on primary cell cultures

Different lesion distribution in calves orally or intratracheally challenged with Mycobacterium bovis: implications for diagnosis

[EN] Animal tuberculosis (TB) remains a major problem in some countries despite the existence of control programmes focused mainly on cattle. In this species, aerogenous transmission is accepted as the most frequent infection route, affecting mainly the respiratory system. Under the hypothesis that the oral route could be playing a more relevant role in transmission, diagnosis and disease persistence than previously thought, this study was performed to assess the course of TB infection in cattle and its effects on diagnosis depending on the route of entry of Mycobacterium bovis. Two groups of five calves each were either endotracheally (EC) or orally (OC) challenged. Necropsies were carried out 12 weeks after challenge except for three OC calves slaughtered 8 weeks later. All animals reacted to the tuberculin skin test and the entire EC group was positive to the interferon-gamma release assay (IGRA) 2 weeks after challenge and thereafter. The first positive IGRA results for OC calves (3/5) were recorded 4 weeks after challenge. Group comparison revealed significant differences in lesion and positive culture location and scoring. TB-compatible gross lesions and positive cultures were more frequently found in the thorax (p < 0.001) and lung (p < 0.05) of EC animals, whereas OC animals presented lesions (p = 0.23) and positive cultures (p < 0.05) mainly located in the abdomen. These results indicate that the infection route seems to be a determining factor for both the distribution and the time needed for the development of visible lesions. Our study suggests that confirmation of TB infection in some skin reactor animals can be problematic if current post-mortem examination and diagnostics are not improvedSIThis study was supported with funds from the Spanish Ministry of Economy and Competitiveness (Research Project AGL2014-56305-C3-3-R) and the Department of Economic Development and Competitiveness of the Basque Government. MS holds a fellowship from the Department of Education of the Basque Government (PRE_2017_2_0043

The Spitzer c2d Survey of Large, Nearby, Interstellar Clouds. IV. Lupus Observed with MIPS

We present maps of 7.78 square degrees of the Lupus molecular cloud complex at 24, 70, and $160\:\mu$m. They were made with the Spitzer Space Telescope's Multiband Imaging Photometer for Spitzer (MIPS) instrument as part of the Spitzer Legacy Program, ``From Molecular Cores to Planet-Forming Disks'' (c2d). The maps cover three separate regions in Lupus, denoted I, III, and IV. We discuss the c2d pipeline and how our data processing differs from it. We compare source counts in the three regions with two other data sets and predicted star counts from the Wainscoat model. This comparison shows the contribution from background galaxies in Lupus I. We also create two color magnitude diagrams using the 2MASS and MIPS data. From these results, we can identify background galaxies and distinguish them from probable young stellar objects. The sources in our catalogs are classified based on their spectral energy distribution (SED) from 2MASS and Spitzer wavelengths to create a sample of young stellar object candidates. From 2MASS data, we create extinction maps for each region and note a strong corresponence between the extinction and the $160\:\mu$m emission. The masses we derived in each Lupus cloud from our extinction maps are compared to masses estimated from $^{13}$CO and C$^{18}$O and found to be similar to our extinction masses in some regions, but significantly different in others. Finally, based on our color-magnitude diagrams, we selected 12 of our reddest candidate young stellar objects for individual discussion. Five of the 12 appear to be newly-discovered YSOs.Comment: 15 pages, 17 figures, uses emulateapj.cls. Accepted for publication in ApJ. A version with high-quality figures can be found at http://peggysue.as.utexas.edu/SIRTF

Public sector reform and demand for human resources for health (HRH)

This article considers some of the effects of health sector reform on human resources for health (HRH) in developing countries and countries in transition by examining the effect of fiscal reform and the introduction of decentralisation and market mechanisms to the health sector. Fiscal reform results in pressure to measure the staff outputs of the health sector. Financial decentralisation often leads to hospitals becoming "corporatised" institutions, operating with business principles but remaining in the public sector. The introduction of market mechanisms often involves the formation of an internal market within the health sector and market testing of different functions with the private sector. This has immediate implications for the employment of health workers in the public sector, because the public sector may reduce its workforce if services are purchased from other sectors or may introduce more short-term and temporary employment contracts. Decentralisation of budgets and administrative functions can affect the health sector, often in negative ways, by reducing resources available and confusing lines of accountability for health workers. Governance and regulation of health care, when delivered by both public and private providers, require new systems of regulation. The increase in private sector provision has led health workers to move to the private sector. For those remaining in the public sector, there are often worsening working conditions, a lack of employment security and dismantling of collective bargaining agreements. Human resource development is gradually being recognised as crucial to future reforms and the formulation of health policy. New information systems at local and regional level will be needed to collect data on human resources. New employment arrangements, strengthening organisational culture, training and continuing education will also be needed

Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. in 18-mo-old rats, such restriction increased glomerulosclerosis. in this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C IS rats. the R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well its significant proteinuria from 12 mo on. in RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was si,significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mu m, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.Universidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Sch Med, Dept Physiol & Biophys, Brookline, MA 02146 USAUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilWeb of Scienc

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

Strawberry GRN forever: insights into the transcriptional regulatory network controlling strawberry fruit ripening and quality

Ripening is a critical step for the development of flavor quality in fruits. This character has significantly declined in many fleshy fruits over recent decades. This is particularly significant in strawberry (Fragaria × ananassa), where current cultivars are derived from a narrow germplasm collection. Improving fruit quality requires two important breakthroughs: 1) a precise understanding of the fruit ripening process that will allow the targeting of relevant genes, and 2) the identification of novel alleles responsible for fruit quality traits. In our project, we aim at the identification and characterization of key transcription factors (TF) involved in fruit ripening regulation and their target genes, in order to infer the Gene Regulatory Network controlling this process. Among them, we have identified two TFs belonging to the NAC (FaRIF) and the BLH9 (FaRPL) family. Functional analyses establishing stable silencing and overexpression lines support that both TFs play a critical role in the regulation of fruit ripening and development. Furthermore, using a stage- and tissue-specific transcriptome analysis, we have identified TFs specifically expressed in the external layer of ripe receptacles of F. vesca fruits, which are involved in the regulation of wax and cuticle formation. Finally, we have implemented the use of the genome-editing tool CRISPR/Cas9 in the cultivated strawberry, which we expect to open opportunities for engineering this species to improve traits of economic importance