Transcription-coupled eviction of histones H2A/H2B governs V(D)J recombination.

Initiation of V(D)J recombination critically relies on the formation of an accessible chromatin structure at recombination signal sequences (RSSs) but how this accessibility is generated is poorly understood. Immunoglobulin light-chain loci normally undergo recombination in pre-B cells. We show here that equipping (earlier) pro-B cells with the increased pre-B-cell levels of just one transcription factor, IRF4, triggers the entire cascade of events leading to premature light-chain recombination. We then used this finding to dissect the critical events that generate RSS accessibility and show that the chromatin modifications previously associated with recombination are insufficient. Instead, we establish that non-coding transcription triggers IgL RSS accessibility and find that the accessibility is transient. Transcription transiently evicts H2A/H2B dimers, releasing 35-40 bp of nucleosomal DNA, and we demonstrate that H2A/H2B loss can explain the RSS accessibility observed in vivo. We therefore propose that the transcription-mediated eviction of H2A/H2B dimers is an important mechanism that makes RSSs accessible for the initiation of recombination

Effect of depth and canopy height on the nursery value of Cystoseira balearica forests for Mediterranean rocky reef fishes

We studied effects of depth and Cystoseira balearica forests canopy height on coastal juvenile fish assemblages of Minorca Island. Results showed a clear differentiation of juvenile fish assemblages due to depth: assemblage in the shallowest range (3-4m) was characterized by higher densities of Thalassoma pavo, deeper ones (6-8, 10-12 m) by higher densities of Coris julis. Smallest juveniles of both species were more abundant within forests displaying the highest canopy height; meanwhile largest juveniles were more abundant within low Cystoseira forests. Also, both species showed predominantly a cryptic behavior on forest of higher canopy height, and a temporal one when canopy was lower. This study supports the importance of preserving healthy Cystoseira forests in order to preserve their nursery value for these two Labrid species0,000

Five key attributes can increase marine protected areas performance for small-scale fisheries management

Marine protected areas (MPAs) have largely proven to be effective tools for conserving marine ecosystem, while socio-economic benefits generated by MPAs to fisheries are still under debate. Many MPAs embed a no-take zone, aiming to preserve natural populations and ecosystems, within a buffer zone where potentially sustainable activities are allowed. Small-scale fisheries (SSF) within buffer zones can be highly beneficial by promoting local socio-economies. However, guidelines to successfully manage SSFs within MPAs, ensuring both conservation and fisheries goals, and reaching a win-win scenario, are largely unavailable. From the peer-reviewed literature, grey-literature and interviews, we assembled a unique database of ecological, social and economic attributes of SSF in 25 Mediterranean MPAs. Using random forest with Boruta algorithm we identified a set of attributes determining successful SSFs management within MPAs. We show that fish stocks are healthier, fishermen incomes are higher and the social acceptance of management practices is fostered if five attributes are present (i.e. high MPA enforcement, presence of a management plan, fishermen engagement in MPA management, fishermen representative in the MPA board, and promotion of sustainable fishing). These findings are pivotal to Mediterranean coastal communities so they can achieve conservation goals while allowing for profitable exploitation of fisheries resources

Functional interaction between Lypd6 and nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain‐containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross‐linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane‐bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine‐induced hippocampal inward currents in rat brain slices and decreases nicotine‐induced extracellular signal‐regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR‐mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post‐natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. [Image: see text] Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine‐induced ERK phosphorylation and attenuates nicotine‐induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain

Effects of Fluids on the Macro- and Microcirculations.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Connecting Variability in Global Transcription Rate to Mitochondrial Variability

The authors demonstrate a connection between variability in the rate of transcription and differences in cellular mitochondrial content

Increased cortical surface area and gyrification following long-term survival from early monocular enucleation

AbstractPurposeRetinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation.MethodsNine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined.ResultsEarly monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation.ConclusionsAltered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss

Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier. RESULTS: The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory' and 'cognition', 'dendrite development' and 'regulation of synaptic plasticity' gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development', 'regulation of synaptic plasticity' and 'positive regulation of synapse assembly' gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant. CONCLUSION: The present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and endocannabinoid mediated pathways in the hippocampal impairments. Taken together the present study provides evidence for the participation of new molecular candidates in the long-term effects of MDMA

Methamphetamine Causes Differential Alterations in Gene Expression and Patterns of Histone Acetylation/Hypoacetylation in the Rat Nucleus Accumbens

Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further