The Academic Senate and University Governance in Canada

This study examines the academic senate within the context of university governance in Canada. Data were obtained from a survey of university senate secretaries on senate structure, composition, and operation, and from a survey of senate members on their perceptions of the senate, their role as senate members, and the nature of their work. The study raises concerns over the effectiveness of the senate and suggests a need to review the senate and its role in contemporary university governance within the context of the current Canadian higher education environment.La présente étude examine le sénat académique dans le cadre de la gouvernance des établissements universitaires au Canada. Des données ont été obtenues à partir d'une enquête menée auprès de secrétaires de sénats universitaires sur la structure, la composition et le fonctionnement des sénats ainsi qu'à partir d'une enquête menée auprès de membres de sénats sur leurs perceptions du sénat, leur rôle en tant que membres de ce dernier et la nature de leur travail. Cette étude soulève des préoccupations sur l'efficacité du sénat et propose la nécessité de réexaminer celui-ci ainsi que le rôle qu'il joue dans la gouvernance des établissements universitaires contemporains, etce dans le contexte de l'environnement actuel de l'enseignement supérieur au Canada

E2F1 induces phosphorylation of p53 that is coincident with p53 accumulation and apoptosis

It has been proposed that the E2F1 transcription factor serves as a link between the Rb/E2F proliferation pathway and the p53 apoptosis pathway by inducing the expression of p19ARF, a protein that regulates p53 stability. We find that although p19ARF contributes to p53 accumulation in response to E2F expression, p19ARF is not required for E2F1-mediated apoptosis. E2F1 can signal p53 phosphorylation in the absence of p19ARF, similar to the observed modifications to p53 in response to DNA damage. These modifications are not observed in the absence of p19ARF following expression of E2F2, an E2F family member that does not induce apoptosis in mouse embryo fibroblasts but can induce p19ARF and p53 protein expression. p53 modification is found to be crucial for E2F1-mediated apoptosis, and this apoptosis is compromised when E2F1 is coexpressed with a p53 mutant lacking many N- and C-terminal phosphorylation sites. Additionally, E2F1-mediated apoptosis is abolished in the presence of caffeine, an inhibitor of phosphatidylinositol 3-kinase-related kinases that phosphorylate p53. These findings suggest that p53 phosphorylation is a key step in E2F1-mediated apoptosis and that this modification can occur in the absence of p19ARF

Artificial Light at Night as a Driver of Evolution Across Urban–Rural Landscapes

Light is fundamental to biological systems, affecting the daily rhythms of bacteria, plants, and animals. Artificial light at night ( ALAN ), a ubiquitous feature of urbanization, interferes with these rhythms and has the potential to exert strong selection pressures on organisms living in urban environments. ALAN also fragments landscapes, altering the movement of animals into and out of artificially lit habitats. Although research has documented phenotypic and genetic differentiation between urban and rural organisms, ALAN has rarely been considered as a driver of evolution. We argue that the fundamental importance of light to biological systems, and the capacity for ALAN to influence multiple processes contributing to evolution, makes this an important driver of evolutionary change, one with the potential to explain broad patterns of population differentiation across urban–rural landscapes. Integrating ALAN ’ s evolutionary potential into urban ecology is a targeted and powerful approach to understanding the capacity for life to adapt to an increasingly urbanized world

Non-paretic Forelimb Training Does Not Interfere with Recovery of Paretic Forelimb Strength After Experimental Middle Cerebral Artery Occlusion

Humans often compensate with their unimpaired (non-paretic) forelimb after surviving a stroke. Research in rats suggests that this can be maladaptive after focal motor cortical strokes. Forelimb weakness is understudied in rodent models of stroke. The purpose of the study is to determine whether behavioral experience with the non-paretic forelimb differentially affects paretic forelimb strength recovery after ischemic injury caused by middle cerebral artery occlusion (MCAo). Because behavioral manipulations can influence patterns of neural connectivity post-stroke, the present study also examined how training with non-paretic limb influenced corticostriatal projections. After training to proficiency with the preferred forelimb on the Isometric Pull Task, rats underwent MCAo in the hemisphere contralateral to this limb. One week after MCAo, rats were probed for initial impairment level and then assigned to either Non-Paretic Limb Training (NPT) or non-training control conditions for 14 days. Paretic limb performance was probed one day later. All rats then received six weeks of Rehabilitative Training (RT). The anterograde tract tracer BDA was then injected into the lesioned hemisphere. Training with the non-paretic limb (NPT) does not interfere with paretic limb recovery on the Isometric Pull Task, increase reliance on the impaired forelimb, or influence ipsi corticostriatal axon quantities after MCAo. Compensatory use of the non-paretic forelimb after strokes involving subcortical damage or cortical damage primarily in the somatosensory region may not be maladaptive for strength. Understanding how behavioral recovery varies with lesion locus could influence clinical management of patients

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and mice

Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended upon this work to develop a simple quantitative measure of forepaw dexterity that is sensitive to lateralized impairments and age-dependent changes. Rodents learn skillful forepaw and digit movements to manage thin pasta pieces, which they eagerly consume. We have previously described methods for quantifying vermicelli handling in rats and showed that the measures are very sensitive to forelimb impairments resulting from unilateral ischemic lesions, middle cerebral artery occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins, D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. & Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)]. Here we present a more detailed protocol for this test in rats and compare it with a newly developed version for mice, the Capellini Handling Test. Rats and mice are videotaped while handling short lengths of uncooked vermicelli or capellini pasta, respectively, with a camera positioned to optimize the view of paw movements. Slow motion video playback allows for the identification of forepaw adjustments, defined as any distinct removal and replacement of the paw, or of any number of digits, on the pasta piece after eating commences. Forepaw adjustments per piece are averaged over trials per each testing session. Repeated testing permits sensitive quantitative analysis of changes in forepaw dexterity over time. Protocols for pre-testing habituation and handling practice, as well as procedures for characterizing atypical handling patterns, are described. Because rats and mice perform the pasta handling tests slightly differently, species-specific differences in administration and scoring of these tests are highlighted. All animal use was in accordance with protocols approved by the University of Texas at Austin Animal Care and Use Committee

The role of DNA methylation in directing the functional organization of the cancer epigenome

The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes.Charles Heidelberger Memorial Fellowshi

Airborne RF Measurement System and Analysis of Representative Flight RF Environment

Environmental radio frequency (RF) data over a broad band of frequencies were needed to evaluate the airspace around several airports. An RF signal measurement system was designed using a spectrum analyzer connected to an aircraft VHF/UHF navigation antenna installed on a small aircraft. This paper presents an overview of the RF measurement system and provides analysis of a sample of RF signal measurement data over a frequency range of 30 MHz to 1000 MHz

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination