3D genome organization during lymphocyte development and activation

Chromosomes have a complex three-dimensional (3D) architecture comprising A/B compartments, topologically associating domains and promoter-enhancer interactions. At all these levels, the 3D genome has functional consequences for gene transcription and therefore for cellular identity. The development and activation of lymphocytes involves strict control of gene expression by transcription factors (TFs) operating in a three-dimensionally organized chromatin landscape. As lymphocytes are indispensable for tissue homeostasis and pathogen defense, and aberrant lymphocyte activity is involved in a wide range of human morbidities, acquiring an in-depth understanding of the molecular mechanisms that control lymphocyte identity is highly relevant. Here we review current knowledge of the interplay between 3D genome organization and transcriptional control during B and T lymphocyte development and antigen-dependent activation, placing special emphasis on the role of TFs

Nurse forecasting in Europe (RN4CAST): Rationale, design and methodology

Contains fulltext : 97171.pdf (postprint version ) (Open Access)BACKGROUND: Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care. METHODS/DESIGN: A multi-country, multilevel cross-sectional design is used to obtain important unmeasured factors in forecasting models including how features of hospital work environments impact on nurse recruitment, retention and patient outcomes. In each of the 12 participating European countries, at least 30 general acute hospitals were sampled. Data are gathered via four data sources (nurse, patient and organizational surveys and via routinely collected hospital discharge data). All staff nurses of a random selection of medical and surgical units (at least 2 per hospital) were surveyed. The nurse survey has the purpose to measure the experiences of nurses on their job (e.g. job satisfaction, burnout) as well as to allow the creation of aggregated hospital level measures of staffing and working conditions. The patient survey is organized in a sub-sample of countries and hospitals using a one-day census approach to measure the patient experiences with medical and nursing care. In addition to conducting a patient survey, hospital discharge abstract datasets will be used to calculate additional patient outcomes like in-hospital mortality and failure-to-rescue. Via the organizational survey, information about the organizational profile (e.g. bed size, types of technology available, teaching status) is collected to control the analyses for institutional differences.This information will be linked via common identifiers and the relationships between different aspects of the nursing work environment and patient and nurse outcomes will be studied by using multilevel regression type analyses. These results will be used to simulate the impact of changing different aspects of the nursing work environment on quality of care and satisfaction of the nursing workforce. DISCUSSION: RN4CAST is one of the largest nurse workforce studies ever conducted in Europe, will add to accuracy of forecasting models and generate new approaches to more effective management of nursing resources in Europe

Oscillatory Activity of the Hippocampus in Prodromal Alzheimer's Disease: A Source-Space Magnetoencephalography Study

Background: In Alzheimer's disease (AD), oscillatory activity of the human brain slows down. However, oscillatory slowing varies between individuals, particularly in prodromal AD. Cortical oscillatory changes have shown suboptimal accuracy as diagnostic markers. We speculated that focusing on the hippocampus might prove more successful, particularly using magnetoencephalography (MEG) for capturing subcortical oscillatory activity. Objective: We explored MEG-based detection of hippocampal oscillatory abnormalities in prodromal AD patients. Methods: We acquired resting-state MEG data of 18 AD dementia patients, 18 amyloid-β-positive amnestic mild cognitive impairment (MCI, prodromal AD) patients, and 18 amyloid-β-negative persons with subjective cognitive decline (SCD). Oscillatory activity in 78 cortical regions and both hippocampi was reconstructed using beamforming. Between-group and hippocampal-cortical differences in spectral power were assessed. Classification accuracy was explored using ROC curves. Results: The MCI group showed intermediate power values between SCD and AD, except for the alpha range, where it was higher than both (p < 0.05 and p < 0.001). The largest differences between MCI and SCD were in the theta band, with higher power in MCI (p < 0.01). The hippocampi showed several unique group differences, such as higher power in the higher alpha band in MCI compared to SCD (p < 0.05). Classification accuracy (MCI versus SCD) was best for absolute theta band power in the right hippocampus (AUC = 0.87). Conclusion: In this MEG study, we detected oscillatory abnormalities of the hippocampi in prodromal AD patients. Moreover, hippocampus-based classification performed better than cortex-based classification. We conclude that a focus on hippocampal MEG may improve early detection of AD-related neuronal dysfunction

Interactions Between a Belowground Herbivore and Primary and Secondary Root Metabolites in Wild Cabbage.

International audiencePlants are attacked by both above- and belowground herbivores. Toxic secondary compounds are part of the chemical defense arsenal of plants against a range of antagonists, and are subject to genetic variation. Plants also produce primary metabolites (amino acids, nutrients, sugars) that function as essential compounds for growth and survival. Wild cabbage populations growing on the Dorset coast of the UK exhibit genetically different chemical defense profiles, even though they are located within a few kilometers of each other. As in other Brassicaceae, the defensive chemicals in wild cabbages constitute, among others, secondary metabolites called glucosinolates. Here, we used five Dorset populations of wild cabbage to study the effect of belowground herbivory by the cabbage root fly on primary and secondary chemistry, and whether differences in chemistry affected the performance of the belowground herbivore. There were significant differences in total root concentrations and chemical profiles of glucosinolates, amino acids, and sugars among the five wild cabbage populations. Glucosinolate concentrations not only differed among the populations, but also were affected by root fly herbivory. Amino acid and sugar concentrations also differed among the populations, but were not affected by root fly herbivory. Overall, population-related differences in plant chemistry were more pronounced for the glucosinolates than for amino acids and sugars. The performance of the root herbivore did not differ among the populations tested. Survival of the root fly was low (<40%), suggesting that other belowground factors may override potential differences in effects related to primary and secondary chemistry

Effects of click polarity on brainstem auditory evoked potentials in cochlear hearing loss: a working hypothesis

The rarefaction-condensation differential potential (RCDP) obtained by subtracting brainstem auditory-evoked potentials (BAEPs) to C clicks from those to R clicks has been studied in 32 normal subjects and 31 cases of cochlear hearing loss. In normal subjects, no RCDP was recorded along the lower 30-55 dB of the JV latency-intensity function, thus defining the pre-RCDP range. The pre-RCDP range was always abolished in losses unmasking BAEPs from lower (<1 kHz) tonotopic regions. When the BAEP originated from higher (< 1 kHz) tonotopic regions, the pre-RCDP range was either reduced or abolished. These results led to a working hypothesis based on single-unit data and stating a dual dependence of polarity effects on variables distributed along the tonotopic and intensity dimensions, with respective break-points at 1 kHz, and at the junction of the tip and tail of unit frequency tuning curves. The 1 kHz break-point could represent the upper frequency limit for phase locking in man. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.SCOPUS: ar.jinfo:eu-repo/semantics/publishe