Mir-125a-3p negatively regulates oligodendrocyte precursor cells maturation and is altered in human multiple sclerosis

In the central nervous system, oligodendrocytes provide support to axons thanks to the production of a myelin sheath. During their maturation oligodendroglial precursors (OPCs) follow a very precise differentiation program, finely orchestrated by transcription factors, epigenetic factors and microRNAs, a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis. Recently, we identified miR-125a-3p as a new actor of oligodendroglial maturation, that could also be involved in the pathological consequences of multiple sclerosis, showing that its over-expression impairs, whereas its silencing promotes, oligodendrocyte maturation (Lecca et al., Sci Rep, 2016). To shed light on the mechanism underlying this effect, we performed a microarray analysis on OPCs after miR-125a-3p over-expression. This analysis suggested that miR-125a-3p is indeed involved in the regulation of biological processes important for OPC maturation, such as cell-cell interaction and morphological differentiation. To evaluate whether miR-125a-3p modulation may influence the progression of remyelination in vivo, we overexpressed the miR-125a-3p by lentiviral approach in a focal lysolecithin-mediated demyelinating lesion in the subcortical white matter of adult mice. Interestingly, also in this case, we found that miRNA-overexpressing OPCs persisted in an immature (i.e. PDGR\u3b1+/NG2+) state. Moreover, we found that miR-125a-3p levels are altered in both brain active lesions and cerebrospinal fluid of multiple sclerosis patients, suggesting that it could be a potential biomarker of disease. The identification of a new miRNA modulating oligodendrocyte differentiation provides new findings about the complex regulation of myelination processes and we postulate that an antago-miRNA for miR-125a-3p may help promoting oligodendrocyte maturation in diseases characterized by impaired myelin repair. Sponsored by Fondazione Italiana Sclerosi Multipla 2013/R-1 project to MPA and by Fondazione Cariplo, grant n\ub0 2014-1207 to DL

Use of ultrasonography exams to determinate the parturition day by Yorkshire canine breed

The purpose of this study was verify the efficacy of ultrasonography to determinate the parturitionday by Yorkshire canine breed also to determinate a measures pattern embryonic vesicle diameter crown rumplenght biparietal diameter body diameter torax diameter abdomen diameter and femur length and also toestablish the linear regression formula to be used by veterinarians for this breed. The length of pregnancy fromthe date of the first mated to the first parturition signs resulted in 63,57 days. So to predict the date of parturitionwas used a multiple linear regression analyses. It was possible determinate a formula to predict the date ofparturition utilizing crown-rump length, biparietal diameter and femur length obtained a major correlation(R 0,998)., ,²Oobjetivo deste trabalho foi verificar a eficácia do método ultra-sonografico visando prever a data departo em cadelas da raça Yorkshire. Também foi objetivo determinar um padrão de mensurações de vesículagestacional, comprimento do feto, diâmetro biparietal, diâmetro do corpo, diâmetro do tórax, diâmetro deabdome e comprimento do fêmur, além de estabelecer uma fórmula de regressão linear para ser utilizada poroutros veterinários ultra-sonografistas nesta raça.Aduração da gestação a partir da data de primeira cópula atéos primeiros sinais de parto resultou numa média de 63,57 dias. Para poder predizer a data de gestação foirealizada uma análise de regressão linear multivariada. Foi possível determinar uma fórmula para prever a datade parturição em cadelas da raça Yorkshire utilizando o comprimento fetal diâmetro biparietal e comprimentodo fêmur obtendo-se significativa correlação (R =0,998)

Metastable chaos in the ammonia ring laser

We report experimental studies of metastable chaos in the far-infrared ammonia ring: laser. When the laser pump power is switched from above chaos threshold to slightly below, chaotic intensity pulsations continue for a varying time afterward before decaying to either periodic or cw emission. The behavior is in good qualitative agreement with that predicted by the Lorenz equations, previously used to describe this laser. The statistical distribution of the duration of the chaotic transient is measured and shown to be in excellent agreement with the Lorenz equations in showing a modified exponential distribution. We also give a brief numerical analysis and graphical visualization of the Lorenz equations in phase space illustrating the boundary between the metastable chaotic and the stable fixed point basins of attraction. This provides an intuitive understanding of the metastable dynamics of the Lorenz equations and the experimental system

Policy masquerading as science: an examination of non-state actor involvement in European risk assessment policy for genetically modified animals

In 2013, at the request of the European Commission, the European Food Safety Authority (EFSA) announced a new risk assessment policy: Guidance on the environmental risks of genetically modified (GM) animals (‘Guidance’). This policy specifies the issues to be addressed in future risk assessments for GM animals. EFSA is the European Commission's scientific arm, responsible for food-related risk assessment. EFSA relies heavily on independent experts and consults non-state actors. Employing expert interviews and documentary analysis, the article explores non-state actor involvement in a traditionally expert domain through a case study. Analysis of EFSA's consultation demonstrates the inability of non-state actors to influence policy. The article argues that despite international legal obligations to develop risk assessment policy, the European Commission failed to recognize the Guidance as policy. When policy masquerades as science, unjustified restrictions are placed on non-state actor involvement and value judgements are cloaked from public scrutiny

Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice

BACKGROUND: The localisation of AMPA and NMDA receptor subunits was studied in a model of degeneration of cervical spinal motoneurons, the wobbler mouse. Cervical regions from early or late symptomatic wobbler mice (4 or 12 weeks of age) were compared to lumbar tracts (unaffected) and to those of healthy mice. RESULTS: No differences were found in the distribution of AMPA and NMDA receptor subunits at both ages. Western blots analysis showed a trend of reduction in AMPA and NMDA receptor subunits, mainly GluR1 and NR2A, exclusively in the cervical region of late symptomatic mice in the triton-insoluble post-synaptic fraction but not whole homogenates. Colocalisation experiments evidenced the expression of GluR1 and NR2A receptors in activated astrocytes from the cervical spinal cord of wobbler mice, GluR2 did not colocalise with GFAP positive cells. No differences were found in the expression of AMPA and NMDA receptor subunits in the lumbar tract of wobbler mice, where neither motoneuron loss nor reactive gliosis occurs. CONCLUSION: In late symptomatic wobbler mice altered levels of GluR1 and NR2A receptor subunits may be a consequence of motoneuron loss rather than an early feature of motoneuron vulnerability

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening