Altered activity-regulated H3K9 acetylation at TGF-beta signaling genes during egocentric memory in Huntington's disease.

Molecular mechanisms underlying cognitive deficits in Huntington's disease (HD), a striatal neurodegenerative disorder, are unknown. Here, we generated ChIPseq, 4Cseq and RNAseq data on striatal tissue of HD and control mice during striatum-dependent egocentric memory process. Multi-omics analyses showed altered activity-dependent epigenetic gene reprogramming of neuronal and glial genes regulating striatal plasticity in HD mice, which correlated with memory deficit. First, our data reveal that spatial chromatin re-organization and transcriptional induction of BDNF-related markers, regulating neuronal plasticity, were reduced since memory acquisition in the striatum of HD mice. Second, our data show that epigenetic memory implicating H3K9 acetylation, which established during late phase of memory process (e.g. during consolidation/recall) and contributed to glia-mediated, TGFß-dependent plasticity, was compromised in HD mouse striatum. Specifically, memory-dependent regulation of H3K9 acetylation was impaired at genes controlling extracellular matrix and myelination. Our study investigating the interplay between epigenetics and memory identifies H3K9 acetylation and TGFß signaling as new targets of striatal plasticity, which might offer innovative leads to improve HD.

Age-related and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in Huntington's disease mice.

Temporal dynamics and mechanisms underlying epigenetic changes in Huntington's disease (HD), a neurodegenerative disease primarily affecting the striatum, remain unclear. Using a slowly progressing knockin mouse model, we profile the HD striatal chromatin landscape at two early disease stages. Data integration with cell type-specific striatal enhancer and transcriptomic databases demonstrates acceleration of age-related epigenetic remodelling and transcriptional changes at neuronal- and glial-specific genes from prodromal stage, before the onset of motor deficits. We also find that 3D chromatin architecture, while generally preserved at neuronal enhancers, is altered at the disease locus. Specifically, we find that the HD mutation, a CAG expansion in the Htt gene, locally impairs the spatial chromatin organization and proximal gene regulation. Thus, our data provide evidence for two early and distinct mechanisms underlying chromatin structure changes in the HD striatum, correlating with transcriptional changes: the HD mutation globally accelerates age-dependent epigenetic and transcriptional reprogramming of brain cell identities, and locally affects 3D chromatin organization.

Epigenetic mechanisms underlying enhancer modulation of neuronal identity, neuronal activity and neurodegeneration.

Neurodegenerative diseases, including Huntington's disease (HD) and Alzheimer's disease (AD), are progressive conditions characterized by selective, disease-dependent loss of neuronal regions and/or subpopulations. Neuronal loss is preceded by a long period of neuronal dysfunction, during which glial cells also undergo major changes, including neuroinflammatory response. Those dramatic changes affecting both neuronal and glial cells associate with epigenetic and transcriptional dysregulations, characterized by defined cell-type-specific signatures. Notably, increasing studies support the view that altered regulation of transcriptional enhancers, which are distal regulatory regions of the genome capable of modulating the activity of promoters through chromatin looping, play a critical role in transcriptional dysregulation in HD and AD. We review current knowledge on enhancers in HD and AD, and highlight challenging issues to better decipher the epigenetic code of neurodegenerative diseases.

New Acridine-Based Tridentate Ligand for Ruthenium(II): Coordination with a Twist.

A new tridentate ligand based on acridine has been synthetized. The central acridine heterocycle bears two pyridine coordinating units at positions 4 and 5. The terdentate 2,7-di- tert-butyl-4,5-di(pyridin-2-yl)acridine (dtdpa) was then coordinated to a ruthenium(II) cation. The corresponding homoleptic complex could only be obtained where both ligands coordinate to the ruthenium in a fac fashion. Thus, a heteroleptic compound (2) was constructed in combination with a terpyridine ligand in order to constrain the ligand to adopt a mer geometry. Such a coordination imposes a dramatic twist on the acridine heterocycle, resulting in an unexpected photophysical behavior. The electrochemical and photophysical properties of both complexes were studied, and the molecular structure of 2 was determined by X-ray diffraction. The two compounds absorb at low energy wavelengths, and a very weak luminescence is detected only for complex 2 in the near-infrared region.

In situ evaluation of the fruit and oil characteristics of the main Lebanese olive germplasm.

BACKGROUND: Very little information is available on the characteristics of the Lebanese olive germplasm. Therefore, the aim of this work was to evaluate the fruit and oil characteristics of the main Lebanese olive varieties (Aayrouni, Abou chawkeh, Baladi, Del and Soury) from two successive crop seasons (2010-2011). RESULTS: All of the genotypes had medium-high oil content in the fruit, indicating their suitability for oil production; Aayrouni had particularly high values. The variety Abou chawkeh also had a high pulp/pit ratio, which is a very desirable trait in table olives. For all the varieties the values of free fatty acids, peroxide values, absorbances in ultraviolet, fatty acid composition, sterol content and composition and erythrodiol + uvaol content of the oils were within the requirements of the International Olive Council's Trade Standard for extra virgin olive oil. The only exception was for the values of Δ-7-stigmastenol in 2011 in Soury and, especially, in Baladi, which were higher than 0.5%. In some cases, stearic and arachidic acids fluctuated around the maximum values allowed. CONCLUSION: The findings of this study provide a first picture of the main characteristics of olives and oils currently produced in Lebanon. © 2015 Society of Chemical Industry.

Modelling and simulation of an infant's whole body plethysmograph.

In this paper, we describe a computational model dedicated to building an apnoea monitoring system for newborn babies. The proposed model is based on whole body plethysmography, which involves non-invasive measurement of lung ventilation indirectly from the pressure deflections generated when a subject breathes inside a chamber of fixed volume (Bert in C R Soc Biol Paris 20:22-23, 1868). The computational model simulates thermal and environmental flow conditions occurring in the neonate chamber, especially steady state flow with heat transfer and carbon dioxide (CO2) transport during the exhalation phase. This permits the variance of all critical parameters and the analysis of their effects on the distributions of interest. The main objective is to study thermal and air quality comfort conditions under which infants can be monitored for long-term periods. The method deploys computational fluid dynamics techniques and parametric modelling which, by allowing input parameters to be modulated, represent a more efficient and flexible analytical tool than previous experimental techniques. Simulation data reveal that the largest flow rates occur in areas near the openings with slight formation of air recirculation zones; temperature distribution shows signs of stratification, with higher temperatures than the supplied air, CO2 distribution presents acceptable air quality level and predicted mean vote index affords a relatively acceptable thermal comfort level. This analytical approach can be considered as innovative, and can find a new application in clinical infant apnoea monitoring in a way that allows determination of the optimal location for placing a sensor to detect respiration activity without any contact with the infant's body, and without any risk, in contrast to available whole body plethysmography techniques previously tested in infants (Fleming et al. in J Appl Physiol 55:1924-1931, 1983).

Ruptura bilateral simultânea do tendäo tricipital em paciente renal crônico em hemodiálise / Simutaneous bilateral rupture of the triceps tendon in a patient in hemodialysis for chronic renal failure

Os autores relatam o caso de uma paciente com insuficiência renal crônica em hemodiálise que apresentou ruptura bilateral simultânea do tendao tricipital, sendo submetida a tratamento cirúrgico, com recuperaçao dos movimentos ativos após três meses.