Differential miRNA expression profiles in cumulus and mural granulosa cells from human pre-ovulatory follicles

BACKGROUND: mural granulosa cells (MGCs) and cumulus cells (CCs) are two specialized cell types that differentiate from a common progenitor during folliculogenesis. Although these two cell types have specialized functions and gene expression profiles, little is known about their microRNA (miRNA) expression patterns.OBJECTIVE: to describe the miRNA profile of mural and cumulus granulosa cells from human pre-ovulatory follicles Methods: using small RNA sequencing, we definedinvestigated the miRNA expression profiles of human primary MGCs and CCs, isolated from healthy women undergoing ovum pick-up for in vitro fertilization (IVF).RESULTS: small RNA sequencing revealed expression of several hundreds of miRNAs in MGCsMGC and CCsCC with 53 miRNAs being significantly differentially expressed between MGCs and CCs. We validated differential expression for miR-146a-5p, miR-149-5p, miR-509-3p and miR-182-5p by RT-qPCR. Analysis of proven targets revealed 37 targets for miR-146a-5p, 43 for miR-182-5p, 2 for miR-509-3p and 9 for miR-149-5p. Gene ontology (GO) analysis for these 4 target gene sets revealed enrichment of 12 GO terms for miR-146a-5p and 10 for miR-182-5p. The GO term ubiquitin-like protein conjugation was enriched within both miRNA target gene sets.CONCLUSION: we generated miRNA expression profiles for MGCs and CCs and identified several differentially expressed miRNAs.</p

Not just a matter of size:a hospital-level risk factor analysis of MRSA bacteraemia in Scotland

Background: Worldwide, there is a wealth of literature examining patient-level risk 6 factors for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. At the hospital-level it is generally accepted that MRSA bacteraemia is more common in larger hospitals. In Scotland, size does not fully explain all the observed variation among hospitals. The aim of this study was to identify risk factors for the presence and rate of MRSA bacteraemia cases in Scottish mainland hospitals. Specific hypotheses regarding hospital size, type and connectivity were examined. Methods: Data from 198 mainland Scottish hospitals (defined as having at least one inpatient per year) were analysed for financial year 2007-08 using logistic regression (Model 1: presence/absence of MRSA bacteraemia) and Poisson regression (Model 2: rate of MRSA bacteraemia). The significance of risk factors representing various measures of hospital size, type and connectivity were investigated. Results: In Scotland, size was not the only significant risk factor identified for the presence and rate of MRSA bacteraemia. The probability of a hospital having at least one case of MRSA bacteraemia increased with hospital size only if the hospital exceeded a certain level of connectivity. Higher levels of MRSA bacteraemia were associated with the large, highly connected teaching hospitals with high ratios of patients to domestic staff. Conclusions: A hospital’s level of connectedness within a network may be a better measure of a hospital’s risk of MRSA bacteraemia than size. This result could be used to identify high risk hospitals which would benefit from intensified infection control measures

Spectroscopic Properties of a Self-Assembled Zinc Porphyrin Tetramer. II. Time-Resolved Fluorescence Spectroscopy.

Excited-state kinetics of complexes of a functionalized zinc tetraphenylporphyrin (ZnTPP) derivative, zinc mono(4-pyridyl)triphenylporphyrin (ZnPyP) in toluene and polystyrene/toluene mixtures have been investigated by time-resolved fluorescence spectroscopy. In addition to the ∼2.0 ns monomer fluorescence lifetime, a ≈ 1.5 ns component was found by applying global analysis to the time-resolved fluorescence decay. The 1.5 ns component is assigned to a cyclic porphyrin tetramer [Part I], with a ≈ 1 ns rotational correlation time at 10 °C. The initial fluorescence anisotropy of the monomer is found to be 0.1. In the tetramer an additional depolarization process occurs with a correlation time of ∼31 ps, resulting in a further decrease of the anisotropy from 0.1 to 0.025. This additional depolarization is ascribed to singlet energy transfer between the porphyrin units that constitute the tetramer. The intramolecular energy transfer processes have been simulated using the Monte Carlo method, yielding rate constants of (26 ± 4 ps

Optimized Trigger for Ultra-High-Energy Cosmic-Ray and Neutrino Observations with the Low Frequency Radio Array

When an ultra-high energy neutrino or cosmic ray strikes the Lunar surface a radio-frequency pulse is emitted. We plan to use the LOFAR radio telescope to detect these pulses. In this work we propose an efficient trigger implementation for LOFAR optimized for the observation of short radio pulses.Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section

Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients

Management of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria. Meta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated. Six studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden. Pre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC

Damage accumulation in thin ruthenium films induced by repetitive exposure to femtosecond XUV pulses below the single shot ablation threshold

The process of damage accumulation in thin ruthenium films exposed to multiple femtosecond XUV free electron laser FEL pulses below the critical angle of reflectance at the Free electron LASer facility in Hamburg FLASH was experimentally analyzed. The multi shot damage threshold is found to be lower than single shot damage threshold. Detailed analysis of the damage morphology and its dependence on irradiation conditions justifies the assumption that cavitation induced by the FEL pulse is the prime mechanism responsible for multi shot damage in optical coating

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

OBJECTIVE: Progranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way. METHODS: We included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes. RESULTS: Language functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA. CONCLUSION: Degeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage

Variations in task constraints shape emergent performance outcomes and complexity levels in balancing

This study investigated the extent to which specific interacting constraints of performance might increase or decrease the emergent complexity in a movement system, and whether this could affect the relationship between observed movement variability and the central nervous system's capacity to adapt to perturbations during balancing. Fifty-two healthy volunteers performed eight trials where different performance constraints were manipulated: task difficulty (three levels) and visual biofeedback conditions (with and without the center of pressure (COP) displacement and a target displayed). Balance performance was assessed using COP-based measures: mean velocity magnitude (MVM) and bivariate variable error (BVE). To assess the complexity of COP, fuzzy entropy (FE) and detrended fluctuation analysis (DFA) were computed. ANOVAs showed that MVM and BVE increased when task difficulty increased. During biofeedback conditions, individuals showed higher MVM but lower BVE at the easiest level of task difficulty. Overall, higher FE and lower DFA values were observed when biofeedback was available. On the other hand, FE reduced and DFA increased as difficulty level increased, in the presence of biofeedback. However, when biofeedback was not available, the opposite trend in FE and DFA values was observed. Regardless of changes to task constraints and the variable investigated, balance performance was positively related to complexity in every condition. Data revealed how specificity of task constraints can result in an increase or decrease in complexity emerging in a neurobiological system during balance performance