RRx-001, A novel dinitroazetidine radiosensitizer.

The 'holy grail' in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer-a systemic chemical/biochemical agent that additively or synergistically sensitizes tumor cells to radiation in the absence of significant toxicity. Similar to the oxygen effect, in which DNA bases modified by reactive oxygen species prevent repair of the cellular radiation damage, these compounds in general magnify free radical formation, leading to the permanent "fixation" of the resultant chemical change in the DNA structure. The purpose of this review is to present the origin story of the radiosensitizer, RRx-001, which emerged from the aerospace industry. The activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews

A Systematic Analysis of miRNA Transcriptome in Marek’s Disease Virus-Induced Lymphoma Reveals Novel and Differentially Expressed miRNAs

Marek’s disease is a lymphoproliferative neoplastic disease of the chicken, which poses a serious threat to poultry health. Marek’s disease virus (MDV)-induced T-cell lymphoma is also an excellent biomedical model for neoplasia research. Recently, miRNAs have been demonstrated to play crucial roles in mediating neoplastic transformation. To investigate host miRNA expression profiles in the tumor transformation phase of MDV infection, we performed deep sequencing in two MDVinfected samples (tumorous spleen and MD lymphoma from liver), and two non-infected controls (non-infected spleen and lymphocytes). In total, 187 and 16 known miRNAs were identified in chicken and MDV, respectively, and 17 novel chicken miRNAs were further confirmed by qPCR. We identified 28 down-regulated miRNAs and 11 up-regulated miRNAs in MDVinfected samples by bioinformatic analysis. Of nine further tested by qPCR, seven were verified. The gga-miR-181a, gga-miR- 26a, gga-miR-221, gga-miR-222, gga-miR-199*, and gga-miR-140* were down-regulated, and gga-miR-146c was upregulated in MDV-infected tumorous spleens and MD lymphomas. In addition, 189 putative target genes for seven differentially expressed miRNAs were predicted. The luciferase reporter gene assay showed interactions of gga-miR-181a with MYBL1, gga-miR-181a with IGF2BP3, and gga-miR-26a with EIF3A. Differential expression of miRNAs and the predicted targets strongly suggest that they contribute to MDV-induced lymphomagenesis

Metabolic Dysfunction Underlying Autism Spectrum Disorder and Potential Treatment Approaches

Autism spectrum disorder (ASD) is characterized by deficits in sociability and communication, and increased repetitive and/or restrictive behaviors. While the etio-pathogenesis of ASD is unknown, clinical manifestations are diverse and many possible genetic and environmental factors have been implicated. As such, it has been a great challenge to identify key neurobiological mechanisms and to develop effective treatments. Current therapies focus on co-morbid conditions (such as epileptic seizures and sleep disturbances) and there is no cure for the core symptoms. Recent studies have increasingly implicated mitochondrial dysfunction in ASD. The fact that mitochondria are an integral part of diverse cellular functions and are susceptible to many insults could explain how a wide range of factors can contribute to a consistent behavioral phenotype in ASD. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), used for nearly a century to treat medically intractable epilepsy, has been shown to enhance mitochondrial function through a multiplicity of mechanisms and affect additional molecular targets that may address symptoms and comorbidities of ASD. Here, we review the evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD as well as emerging co-morbid models of epilepsy and autism. Future research directions aimed at validating such therapeutic approaches and identifying additional and novel mechanistic targets are also discussed

Experimental and theoretical cross sections for molecular-frame electron-impact excitation-ionization of D 2

We present both experimental and theoretical results for the dissociative ionization of D2 molecules induced by electron impact. Cross sections are determined in the molecular frame and are fully differential in the energies and emission angles of the di

Brain-State Dependent Stimulation boosts functional recovery following stroke

This is the peer reviewed version of the following article: “Brain-State Dependent Stimulation boosts functional recovery following stroke”, which has been published in final form at http://dx.doi.org/10.1002/ana.25375. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived.Objective Adjuvant protocols devised to enhance motor recovery in subacute stroke patients have failed to show benefits with respect to classic therapeutic interventions. Here we evaluate the efficacy of a novel brain-state dependent intervention based on known mechanisms of memory and learning, that is integrated as part of the weekly rehabilitation program in subacute stroke patients. Methods Twenty-four hospitalized subacute stroke patients were randomly assigned to two intervention groups; 1. The associative group received thirty pairings of a peripheral electrical nerve stimulus (ES) such that the generated afferent volley arrived precisely during the most active phase of the motor cortex as patients attempted to perform a movement; 2. In the control group the ES intensity was too low to generate a stimulation of the nerve. Functional (including the lower extremity Fugl-Meyer assessment (LE-FM; primary outcome measure)) and neurophysiological (changes in motor evoked potentials (MEPs)) assessments were performed prior to and following the intervention period. Results The associative group significantly improved functional recovery with respect to the control group (median (interquartile range) LE-FM improvement: 6.5 (3.5-8.25) and 3 (0.75-3), respectively; p=0.029). Significant increases in MEP amplitude were seen following all sessions in the associative group only (p’s≤0.006). Interpretation This is the first evidence of a clinical effect of a neuromodulatory intervention in the subacute phase of stroke. This was evident with relatively few repetitions in comparison to available techniques, making it a clinically-viable approach. The results indicate the potential of the proposed neuromodulation system in daily clinical routine for stroke rehabilitation. This article is protected by copyright. All rights reserved.Kong Christian den Tiendes Fond (39/2016

Dynamical (e, 2e) Studies Using Tetrahydrofuran As a DNA Analog

Triple differential cross sections for the electron-impact ionization of the outer valence orbital of tetrahydrofuran have been measured using the (e, 2e) technique. The measurements have been performed with coplanar asymmetric kinematics, at an incident electron energy of 250 eV and at an ejected electron energy of 10 eV, over a range of momentum transfers. The experimental results are compared with theoretical calculations carried out using the molecular three-body distorted wave model. The results obtained are important for gaining an understanding of electron driven processes at a molecular level and for modeling energy deposition in living tissue