Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration.

In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5hmC). We generated genome-wide 5hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5hmC changes that are associated with distinct signaling pathways.

Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors.

Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo.

Reduction of biological response modifiers in the supernatant of washed paediatric red blood cells.

Background: Washing of red blood cells (RBC) can reduce unwanted biological response modifiers (BRMs) that can mediate transfusion complications in infants. The aim of this study was to examine the in vitro quality and the changes in BRMs following washing in paediatric RBC units.

Materials And Methods: A pool and split design was used to prepare RBC (either 1 or 4 days old; n = 26 pairs).

Nickel-Catalyzed Facile [2+2+2] Cyclotrimerization of Unactivated Internal Alkynes to Polysubstituted Benzenes.

A catalytic [2+2+2] cyclotrimerization of unactivated internal alkynes providing cyclotrimerization products in excellent yields with high regioselectivity is described. The transformation is accomplished by using a simple catalytic mixture comprising Ni(acac) , an imidazolium salt and a Grignard reagent at room temperature or 60 °C for 20 min or 1 h.

Structure of the NS2B-NS3 protease from Zika virus after self-cleavage.

The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.

Self-Paced Reaching after Stroke: A Quantitative Assessment of Longitudinal and Directional Sensitivity Using the H-Man Planar Robot for Upper Limb Neurorehabilitation.

Technology aided measures offer a sensitive, accurate and time-efficient approach for the assessment of sensorimotor function after neurological insult compared to standard clinical assessments. This study investigated the sensitivity of robotic measures to capture differences in planar reaching movements as a function of neurological status (stroke, healthy), direction (front, ipsilateral, contralateral), movement segment (outbound, inbound), and time (baseline, post-training, 2-week follow-up) using a planar, two-degrees of freedom, robotic-manipulator (H-Man). Twelve chronic stroke (age: 55 ± 10.

Aberrant H3.3 dynamics in NAc promote vulnerability to depressive-like behavior.

Human major depressive disorder (MDD), along with related mood disorders, is among the world's greatest public health concerns; however, its pathophysiology remains poorly understood. Persistent changes in gene expression are known to promote physiological aberrations implicated in MDD. More recently, histone mechanisms affecting cell type- and regional-specific chromatin structures have also been shown to contribute to transcriptional programs related to depressive behaviors, as well as responses to antidepressants.

An exploration of the applicability of the refined disease risk index and its integration with other independent risk factors for individualized prognostication.

The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication.

Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment.

Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF-α1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex.

The Chromogranin A-derived sympathomimetic serpinin depresses myocardial performance in teleost and amphibian hearts.

Chromogranin A (CgA) is an acidic protein co-stored with catecholamines, hormones and neuropeptides in the secretory granules of endocrine, neuronal and other cell types (including cardiomyocytes). Proteolytic cleavage in the C terminus of CgA generates a 2.9kDa peptide named serpinin (Serp; Ala26Leu) that can be modified at its N terminus to form a pyroglutamate residue (pGlu-Serp).

Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis.

Importance: The association of nonmotor features and Parkinson disease (PD) is increasingly recognized. Evidence suggests that inflammation may play a role in PD pathologic features and symptoms.

Objective: To quantitatively summarize the peripheral inflammatory cytokine data available for patients with PD.

Association of Peripheral Blood Levels of Brain-Derived Neurotrophic Factor With Autism Spectrum Disorder in Children: A Systematic Review and Meta-analysis.

Importance: Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) may be implicated in the developmental outcomes of children with autism spectrum disorder (ASD).

Objective: To use meta-analysis to determine whether children with ASD have altered peripheral blood levels of BDNF.

Data Source: A systematic search of PubMed, PsycINFO, and Web of Science was performed for English-language literature through February 7, 2016.

Telomerase reverse transcriptase promotes cancer cell proliferation by augmenting tRNA expression.

Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes telomerase activity in the majority of human cancers. Here, we found that ectopic TERT expression increases cell proliferation, while acute reductions in TERT levels lead to a dramatic loss of proliferation without any change in telomere length, suggesting that the effects of TERT could be telomere independent. We observed that TERT determines the growth rate of cancer cells by directly regulating global protein synthesis independently of its catalytic activity.

Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons.

Basic Fibroblast growth factor (FGF2) is important in development and maintenance of central nervous system function. Studies have demonstrated that low molecular weight (LMW) FGF2 is a neuroprotective factor against various insults in vivo and in vitro. In the present study we investigated the neuroprotective effects of high molecular weight (HMW) and LMW FGF2 against amyloid beta-induced neurotoxicity.

Derivation of Transgene-Free Induced Pluripotent Stem Cells from a Single Drop of Blood.

Human-induced pluripotent stem cells (hiPSCs) have great potential for future use in therapeutic regenerative medicine. Based on the current protocol for deriving hiPSCs, invasive procedures such as skin biopsies and venipuncture are required for obtaining donor samples. Herein, we present a detailed protocol for deriving hiPSCs from human finger-prick (FP) blood.

Single-cell multimodal profiling reveals cellular epigenetic heterogeneity.

Sample heterogeneity often masks DNA methylation signatures in subpopulations of cells. Here, we present a method to genotype single cells while simultaneously interrogating gene expression and DNA methylation at multiple loci. We used this targeted multimodal approach, implemented on an automated, high-throughput microfluidic platform, to assess primary lung adenocarcinomas and human fibroblasts undergoing reprogramming by profiling epigenetic variation among cell types identified through genotyping and transcriptional analysis.

Neuroserpin Attenuates HO-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways.

Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits HO-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays.

Neuronal Deletion of Kmt2a/Mll1 Histone Methyltransferase in Ventral Striatum is Associated with Defective Spike-Timing-Dependent Striatal Synaptic Plasticity, Altered Response to Dopaminergic Drugs, and Increased Anxiety.

Lysine (K) methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4 methylation, a histone modification enriched at promoters and enhancers, are widely expressed throughout the brain, but molecular and cellular phenotypes in subcortical areas remain poorly explored. We report that Kmt2a conditional deletion in postnatal forebrain is associated with excessive nocturnal activity and with absent or blunted responses to stimulant and dopaminergic agonist drugs, in conjunction with near-complete loss of spike-timing-dependent long-term potentiation in medium spiny neurons (MSNs). Selective ablation of Kmt2a, but not the ortholog Kmt2b, in adult ventral striatum/nucleus accumbens neurons markedly increased anxiety scores in multiple behavioral paradigms.

Treatment of cerebral vasospasm with self-expandable retrievable stents: proof of concept.

Objective: To report our preliminary experience with the use of stent retrievers to cause vasodilation in patients with delayed cerebral vasospasm secondary to subarachnoid hemorrhage.

Methods: Four patients from two different high volume neurointerventional centers developed cerebral vasospasm following subarachnoid hemorrhage. In addition to standard techniques for the treatment of cerebral vasospasm, we used commercially available stent retrievers (Solitaire and Capture stent retrievers) to treat the vasospastic segment including M2, M1, A2, and A1.

Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform.

In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation.

Vasorelaxation Study and Tri-Step Infrared Spectroscopy Analysis of Malaysian Local Herbs.

Objectives: The aim of this paper is to investigate the activities of Malaysian local herbs (Clinacanthus nutans Lindau, Strobilanthes crispus, Murdannia bracteata, Elephantopus scaber Linn., Pereskia bleo, Pereskia grandifolia Haw., Vernonia amygdalina, and Swietenia macrophylla King) for anti-hypertensive and vasorelaxant activity.

Metastatic follicular thyroid carcinoma: a case report.

Objective: A case of oral metastatic follicular thyroid carcinoma is presented.

Background: Metastatic tumours are more frequent in older individuals and can be the only sign/symptom of an undiagnosed primary malignancy.

Case Report: A 69-year-old lady presented with an enlarging mandibular swelling.