Identification of Sequence Specificity of 5-Methylcytosine Oxidation by Tet1 Protein with High-Throughput Sequencing.

Tet (ten-eleven translocation) family proteins have the ability to oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC). However, the oxidation reaction of Tet is not understood completely. Evaluation of genomic-level epigenetic changes by Tet protein requires unbiased identification of the highly selective oxidation sites.

Mycobacterium tuberculosis Infection Induces HDAC1-Mediated Suppression of IL-12B Gene Expression in Macrophages.

Downregulation of host gene expression is one of the many strategies employed by intracellular pathogens such as Mycobacterium tuberculosis (MTB) to survive inside the macrophages and cause disease. The underlying molecular mechanism behind the downregulation of host defense gene expression is largely unknown. In this study we explored the role of histone deacetylation in macrophages in response to infection by virulent MTB H37Rv in manipulating host gene expression.

C1q Nephropathy: The Unique Underrecognized Pathological Entity.

C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and proliferative glomerulonephritis.

Revisiting Cardiac Cellular Composition.

Rationale: Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration.

Objective: To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.

Methods And Results: Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart.

Cerebral CT Venography Using a 320-MDCT Scanner With a Time-Density Curve Technique and Low Volume of Contrast Agent: Comparison With Fixed Time-Delay Technique.

Objective: The purpose of this study was to compare a cerebral CT venography (CTV) technique performed on a 320-MDCT scanner with the use of a time-density curve (TDC) and a small volume of IV contrast medium (35 mL, with 15 mL used for the test bolus) with CTV performed using an established reference technique in which scanning is performed at a fixed time delay of 30 seconds with the use of a larger volume of contrast medium (100 mL).

Materials And Methods: The time of peak enhancement was determined from the TDC generated from a scan in which a test bolus dose was used. CTV was performed at the time of peak enhancement.

A study to evaluate cephalometric hard tissue profile of Tamil population for orthognathic surgery.

The primary aim of this study is to compare, the cephalometric hard tissue profile values and analysis between Tamil and Caucasian population. The study also aims to create a better understanding in the facial proportions of Tamil Nadu population and to have better diagnosis and treatment planning for orthognathic surgery for Tamil population in Tamil Nadu.

Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections.

Methods: This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation.

Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase.

We isolated an 8 kDa mycobacterial hypothetical protein, Rv3423.1, from the chromatin of human macrophages infected with Mycobacterium tuberculosis H37Rv. Bioinformatics predictions followed by in vitro biochemical assays with purified recombinant protein showed that Rv3423.

Investigation on the temporal variation and source tracking of faecal bacteria in a forest dominated watershed (Comox Lake), British Columbia, Canada.

Aims: The aims of this study were to investigate the temporal variation in Escherichia coli density and its sources at the drinking water intake of Comox Lake for a period of 3 years (2011-2013).

Methods And Results: Density of E. coli was assessed by standard membrane filtration method.

Accuracy of four-dimensional CT angiography in detection and characterisation of arteriovenous malformations and dural arteriovenous fistulas.

A retrospective review was made to assess the accuracy of four dimensional CT angiogram (4D-CTA) in diagnosis of arteriovenous malformations (AVM) and dural arteriovenous fistulas (DAVF), with catheter-based digital-subtraction angiogram (DSA) being gold standard. 33 pairs of investigations (DSA and 4D-CTA) were performed primarily for suspicion of AVM/DAVF. Based on blinded reports, sensitivity and specificity for detection of AVM/DAVF were 77% (95% CI: 46-95%) and 100% (95% CI: 83-100%) respectively.

Selective Targeting of the KRAS Codon 12 Mutation Sequence by Pyrrole-Imidazole Polyamide seco-CBI Conjugates.

Mutation of KRAS is a key step in many cancers. Mutations occur most frequently at codon 12, but the targeting of KRAS is notoriously difficult. We recently demonstrated selective reduction in the volume of tumors harboring the KRAS codon 12 mutation in a mouse model by using an alkylating hairpin N-methylpyrrole-N-methylimidazole polyamide seco-1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one conjugate (conjugate 4) designed to target the KRAS codon 12 mutation sequence.

Magnetic resonance imaging of the subthalamic nucleus for deep brain stimulation.

The subthalamic nucleus (STN) is one of the most important stereotactic targets in neurosurgery, and its accurate imaging is crucial. With improving MRI sequences there is impetus for direct targeting of the STN. High-quality, distortion-free images are paramount.

A Study on the Influence of the Osteotomy Slope on Bony Changes after Advancement Genioplasty.

Introduction: The slope of the osteotomy used for the genioplasty dictates the vertical change. The horizontal bony changes after advancement genioplasty are not identical to the intercortical bony changes, because the variety of osteotomy slopes result in different vertical changes.

Material And Methodology: Ten of these patients had additional osteotomies as follows: five maxillary, three mandibular and two both maxillary and mandibular.

Novel use of 4D-CTA in imaging of intranidal aneurysms in an acutely ruptured arteriovenous malformation: is this the way forward?

Ruptured arteriovenous malformation (AVM) is a frequent cause of intracranial hemorrhage. The presence of associated aneurysms, especially intranidal aneurysms, is considered to increase the risk of re-hemorrhage. We present two cases where an intranidal aneurysm was demonstrated on four-dimensional CT angiography (time-resolved CT angiography) (4D-CTA).

Novel use of 4D-CTA in imaging of intranidal aneurysms in an acutely ruptured arteriovenous malformation: is this the way forward?

Ruptured arteriovenous malformation (AVM) is a frequent cause of intracranial hemorrhage. The presence of associated aneurysms, especially intranidal aneurysms, is considered to increase the risk of re-hemorrhage. We present two cases where an intranidal aneurysm was demonstrated on four-dimensional CT angiography (time-resolved CT angiography) (4D-CTA).

Initial experience of coiling cerebral aneurysms using the new Comaneci device.

We present our initial patient experience with an innovative temporary bridging device, the Comaneci (Rapid Medical, Israel), to assist in the coiling of cerebral aneurysms. The Comaneci device confers the same benefits as balloon remodeling but without the risks of parent artery occlusion. This alleviates time pressure on the clinician, and could reduce the risk of parent artery thrombosis.

Initial experience of coiling cerebral aneurysms using the new Comaneci device.

We present our initial patient experience with an innovative temporary bridging device, the Comaneci (Rapid Medical, Israel), to assist in the coiling of cerebral aneurysms. The Comaneci device confers the same benefits as balloon remodeling but without the risks of parent artery occlusion. This alleviates time pressure on the clinician, and could reduce the risk of parent artery thrombosis.

A Synthetic DNA-Binding Domain Guides Distinct Chromatin-Modifying Small Molecules to Activate an Identical Gene Network.

Synthetic dual-function ligands targeting specific DNA sequences and histone-modifying enzymes were applied to achieve regulatory control over multi-gene networks in living cells. Unlike the broad array of targeting small molecules for histone deacetylases (HDACs), few modulators are known for histone acetyltransferases (HATs), which play a central role in transcriptional control. As a novel chemical approach to induce selective HAT-regulated genes, we conjugated a DNA-binding domain (DBD) "I" to N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide (CTB), an artificial HAT activator.

Adherence to Insulin Pen Therapy Is Associated with Reduction in Healthcare Costs Among Patients with Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus is a chronic metabolic disorder that poses a significant economic burden on the US healthcare system associated with direct and indirect medical costs, loss of productivity, and premature mortality.

Objectives: To determine whether increased adherence to therapy among patients with type 2 diabetes who use an insulin pen is associated with reduced healthcare costs, and to describe the overall healthcare costs of patients with type 2 diabetes.

Methods: This retrospective claims database analysis used the Truven Health MarketScan Commercial and Medicare Supplemental databases to identify patients diagnosed with type 2 diabetes with at least 1 insulin pen prescription claim between January 2006 and September 2010.

Distal access using hyperflexible atraumatic distal tip with optimized proximal stability of the Benchmark intracranial guide catheter for the treatment of cerebral vascular diseases: a technical note.

Background: A stable guide catheter position within the intracranial vasculature is critical for safe, successful endovascular treatment.

Objective: To present ourinitial experience with the 0.071 inch inner diameter Benchmark guide catheter used in the treatment of intracranial cerebrovascular pathologies, demonstrating its safety and efficacy.

Glucocorticoid usage in giant cell arteritis over six decades (1950 to 2009).

Objectives: To evaluate the trends in glucocorticoid (GC) therapy in patients with giant cell arteritis (GCA).

Methods: Using a population-based inception cohort, GC therapy details were collected for all patients with GCA diagnosed between 1950-2009. GC usage for patients diagnosed with GCA between 1980-2009 was compared to those diagnosed between 1950-1979.

The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United States.

Background/purpose: Little information exists on the comparative patient and economic burden of chronic widespread pain (CWP) and fibromyalgia (FM) in the United States.

Methods: This multistage, observational study included an online screening survey of a large geographically diverse US sample to assess CWP status, a physician/site visit to determine FM diagnosis, and an online subject questionnaire to capture clinical characteristics, pain, health status, functioning, sleep, healthcare resource use (HRU), productivity, and costs. Based on the screener and physician evaluation, mutually exclusive groups of subjects without CWP (CWP-), with CWP but without FM (CWP+), and with confirmed FM were identified.

A Synthetic Transcriptional Activator of Genes Associated with the Retina in Human Dermal Fibroblasts.

Small molecules capable of modulating epigenetic signatures can activate the transcription of tissue-restricted genes in a totally unrelated cell type and have potential use in epigenetic therapy. To provide an example for an initial approach, we report here on one synthetic small-molecule compound-termed "SAHA-PIP X"-from our library of conjugates. This compound triggered histone acetylation accompanied by the transcription of retinal-tissue-related genes in human dermal fibroblasts (HDFs).

Structural studies on Mycobacterium tuberculosis RecA: molecular plasticity and interspecies variability.

Structures of crystals of Mycobacterium tuberculosis RecA, grown and analysed under different conditions, provide insights into hitherto underappreciated details of molecular structure and plasticity. In particular, they yield information on the invariant and variable features of the geometry of the P-loop, whose binding to ATP is central for all the biochemical activities of RecA. The strengths of interaction of the ligands with the P-loop reveal significant differences.