The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

Copyright © 2014 Al-Mahdawi, Anjomani Virmouni and Pook. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC) modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC), which is formed by oxidation of 5mC by ten-eleven translocation (TET) enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS). The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA), Huntington's disease (HD), and Parkinson's disease (PD).Sara Anjomani Virmouni was supported by funding to Mark A. Pook from the Friedreich’s Ataxia Research Alliance(FARA)

Genomic organization and chromosomal localization of the murine 2 P domain potassium channel gene Kcnk8: conservation of gene structure in 2 P domain potassium channels.

A 2 P domain potassium channel expressed in eye, lung, and stomach, Kcnk8, has recently been identified. To initiate further biochemical and genetic studies of this channel, we assembled the murine Kcnk8 cDNA sequence, characterized the genomic structure of the Kcnk8 gene, determined its chromosomal localization, and analyzed its activity in a Xenopus laevis oocyte expression system. The composite cDNA has an open reading frame of 1029 bp and encodes a protein of 343 amino acids with a predicted molecular mass of 36 kDa. Structure analyses predict 2 P domains and four potential transmembrane helices with a potential single EF-hand motif and four potential SH3-binding motifs in the COOH-terminus. Cloning of the Kcnk8 chromosomal gene revealed that it is composed of three exons distributed over 4 kb of genomic DNA. Genome database searching revealed that one of the intron/exon boundaries identified in Kcnk8 is present in other mammalian 2 P domain potassium channels genes and many C. elegans 2P domain potassium channel genes, revealing evolutionary conservation of gene structure. Using fluorescence in situ hybridization, the murine Kcnk8 gene was mapped to chromosome 19, 2B, the locus of the murine dancer phenotype, and syntenic to 11q11-11q13, the location of the human homologue. No significant currents were generated in a Xenopus laevis oocyte expression system using the composite Kcnk8 cDNA sequence, suggesting, like many potassium channels, additional channel subunits, modulator substances, or cellular chaperones are required for channel function

Vitrification of human immature oocytes before and after in vitro maturation: a review

The use of immature oocytes subjected to in vitro maturation (IVM) opens interesting perspectives for fertility preservation where ovarian reserves are damaged by pathologies or therapies, as in PCO/PCOS and cancer patients. Human oocyte cryopreservation may offer some advantages compared to embryo freezing, such as fertility preservation in women at risk of losing fertility due to oncological treatment or chronic disease, egg donation and postponing childbirth. It also eliminates religious and/or other ethical, legal, and moral concerns of embryo freezing. In addition, a successful oocyte cryopreservation program could eliminate the need for donor and recipient menstrual cycle synchronization. Recent advances in vitrification technology have markedly improved the oocyte survival rate after warming, with fertilization and implantation rates comparable with those of fresh oocytes. Healthy live births can be achieved from the combination of IVM and vitrification, even if vitrification of in vivo matured oocytes is still more effective. Recently, attention is given to highlight whether vitrification procedures are more successful when performed before or after IVM, on immature GV-stage oocytes, or on in vitro matured MII-stage oocytes. In this review, we emphasize that, even if there are no differences in survival rates between oocytes vitrified prior to or post-IVM, reduced maturation rates of immature oocytes vitrified prior to IVM can be, at least in part, explained by underlying ultrastructural and biomolecular alterations

Bench Blasting Design for Optimum Recovery of Blocks in Dimension Stone Quarries: A Case Study of Crushed Rock Industry, Supare-Nigeria

Dimension stone quarry is believed to be type of mining operation that always result to low recovery since what is expected from the extracting operation is a cubical block with no fracture. It is noticed that majority of the damage in the natural blocks are always from poor extraction method. In aggregate quarry, series of work have been done on powder factor that gives economical blasting. In this research work, breaking factor is used in place of powder factor since breaking is required not powder. The aim of this research work is to establish a standard breaking factor for bench blasting in dimension quarries that will improve recovery.Two cases were considered. In case 1, gun powder is used for basal cutting. Of the seven patterns considered, pattern3 gives highest recovery (70%) with breaking factor of 23.15g/m3 (i.e. 5kg of Gun powder for (6 by 6 by 6) m bench design). In the case 2, dynacord is used for basal cutting. Of the four patterns considered, pattern 2 gives highest recovery (55%) with breaking factor of 15g/m3 ( i.e. 3.24kg of explosive for (6 by 6 by 6) m bench design.Keywords: Extracting, powder factor, aggregate, recovery, breaking facto

Hybrid solid state qubits: the powerful role of electron spins

We review progress on the use of electron spins to store and process quantum information, with particular focus on the ability of the electron spin to interact with multiple quantum degrees of freedom. We examine the benefits of hybrid quantum bits (qubits) in the solid state that are based on coupling electron spins to nuclear spin, electron charge, optical photons, and superconducting qubits. These benefits include the coherent storage of qubits for times exceeding seconds, fast qubit manipulation, single qubit measurement, and scalable methods for entangling spatially separated matter-based qubits. In this way, the key strengths of different physical qubit implementations are brought together, laying the foundation for practical solid-state quantum technologies.Comment: 54 pages, 7 figure

Clinical Profile of Patients with Osteoarthritis of the Knee A Study of 162 Cases

One hundred sixty two patients of osteoarthritis (OA)knee were studied to describe their clinical profile. Thepatients were included according to the criteria developedby the American College of Rheumatology. Detailedhistory, clinical examination and X-rays were carried out.The data were analysed statistically and the results wereexpressed in percentage and frequency. In this study, 96(59.3%) were male and 66 (40.7%) were female. Themean age of the subject was 53.73 ± 11.35 years. Mostof the patients of were in the age group of 50 to 59 years.Maximum number of females in the age group of 35 to45 years was affected. Most of the males were affectedin the later ages, between 55 to 65 years. Most of thepatients were middle class (68.5%) and housewives(35.8%). Mean height was 159.99 ± 8.12 cm and meanweight was 63.34 ± 11.60 kg. Mean duration of symptomswas 25.25 ± 38.85 months. Most patients gave the historyof gradual onset of the pain (87.7%). Most of the patientshad no morning stiffness in the knee (90.1%). Morningstiffness was present in 9.3% but it was for less than onehour. Maximum patients had intermittent pain (53.7%)but 46.3% patients had constant pain. By this study, itcan be concluded that OA knee is commoner in malesbut females develop it earlier in the life than the males

Hybrid electric vehicle fuel minimization by DC-DC converter dual-phase-shift control

The paper introduces an advanced DC-link variable voltage control methodology that improves significantly the fuel economy of series Hybrid Electric Vehicles (HEVs). The DC-link connects a rectifier, a Dual Active Bridge (DAB) DC-DC converter and an inverter, interfacing respectively the two sources and the load in a series HEV powertrain. The introduced Dual Phase Shift (DPS) proportional voltage conversion ratio control scheme is realized by manipulating the phase shifts of the gating signals in the DAB converter, to regulate the amount of DAB converter power flow in and out of the DC-link. Dynamic converter efficiency models are utilized to account for switching, conduction, copper and core losses. The control methodology is proposed on the basis of improving the individual efficiency of the DAB converter but with its parameters tuned to minimize the powertrain fuel consumption. Since DPS control has one additional degree of freedom as compared to Single Phase Shift (SPS) voltage control schemes, a Lagrange Multiplier optimization method is applied to minimize the leakage inductance peak current, the main cause for switching and conduction losses. The DPS control scheme is tested in simulations with a full HEV model and two associated conventional supervisory control algorithms, together with a tuned SPS proportional voltage conversion ratio control scheme, against a conventional PI control in which the DC-link voltage follows a constant reference. Nonlinear coupling difficulties associated with the integration of varying DC-link voltage in the powertrain are also exposed and addressed

Implementation of Quantum Gates via Optimal Control

Starting with the basic control system model often employed in NMR pulse design, we derive more realistic control system models taking into account effects such as off-resonant excitation for systems with fixed inter-qubit coupling controlled by globally applied electromagnetic fields, as well as for systems controlled by a combination of a global fields and local control electrodes. For both models optimal control is used to find controls that implement a set of two- and three-qubit gates with fidelity greater than 99.99%. While in some cases the optimal pulses obtained appear to be surprisingly simple and experimentally realistic, the results also show that the "optimal" pulses obtained in other cases are experimentally infeasible, and more sophisticated parametrization of the control fields and numerical algorithms are needed.Comment: 10 pages, 4 figure