Motor neuron disease due to neuropathy target esterase gene mutation: Clinical features of the index families

Recently, we reported that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive motor neuron disease (NTE-MND). We describe clinical, neurophysiologic, and neuroimaging features of affected subjects in the index families. NTE-MND subjects exhibited progressive lower extremity spastic weakness that began in childhood and was later associated with atrophy of distal leg and intrinsic hand muscles. NTE-MND resembles Troyer syndrome, except that short stature, cognitive impairment, and dysmorphic features, which often accompany Troyer syndrome, are not features of NTE-MND. Early onset, symmetry, and slow progression distinguish NTE-MND from typical amyotrophic lateral sclerosis. NTE is implicated in organophosphorus compound–induced delayed neurotoxicity (OPIDN). NTE-MND patients have upper and lower motor neuron deficits that are similar to OPIDN. Motor neuron degeneration in subjects with NTE mutations supports the role of NTE and its biochemical cascade in the molecular pathogenesis of OPIDN and possibly other degenerative neurologic disorders. Muscle Nerve, 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78477/1/21777_ftp.pd

WOULD DISTANCE EDUCATION BE THE ANSWER FOR A PANDEMIC TIME?

This article aims to reflect on the educational policies, for higher education, enacted in the period of Coronavirus pandemic and the conditions for the provision of Distance Education (DE) in an emergency character of the best quality. The researchers tried to understand in this work, as a research problem, if DE would be the answer for a pandemic time. The methodology is based on Bogdan and Biklen (1994) and Creswell (2010; 2014) which deal with the qualitative paradigm. Gil (2008) contributes to this work with the exploratory approach. As a source of data, this work used the educational legal bases researches already consolidated in distance education, and the daily work of the authors as teachers in federal public institutions, as well as the process they experienced in facing the coronavirus pandemic regarding education practices remote / online / distance created based on legislation that allowed face-to-face classes to be replaced by distance activities.El objetivo de este artículo es el de reflexionar acerca de las políticas educacionales, para la enseñanza superior, decretadas en período de pandemia de coronavirus y las condiciones concretas para la oferta de la Educación a Distancia (EaD), en carácter de emergencia, de la mejor calidad. Las investigadoras buscan reflexionar, en este trabajo, ¿si sería la EaD la respuesta para una época de pandemia? La metodología está basada en Bogdan y Biklen (1994) y Creswell (2010; 2014) que tratan del paradigma cualitativo. Gil (2008) contribuye con el abordaje exploratorio. Como fuente de datos fueran utilizadas las bases legales educacionales, investigaciones ya consolidadas en EaD y el cotidiano del trabajo de las autoras, como docentes en instituciones públicas federales, así como el proceso por ellas vivenciado en el enfrentamiento de la pandemia del coronavirus, en lo que se refiere a las prácticas de educación remota/online/a distancia, creadas a partir de la legislación que permitió que las clases presenciales pudiesen ser sustituidas por actividades a distancia.This article aims to reflect on the educational policies, for higher education, enacted in the period of Coronavirus pandemic and the conditions for the provision of Distance Education (DE) in an emergency character of the best quality. The researchers tried to understand in this work, as a research problem, if DE would be the answer for a pandemic time. The methodology is based on Bogdan and Biklen (1994) and Creswell (2010; 2014) which deal with the qualitative paradigm. Gil (2008) contributes to this work with the exploratory approach. As a source of data, this work used the educational legal bases researches already consolidated in distance education, and the daily work of the authors as teachers in federal public institutions, as well as the process they experienced in facing the coronavirus pandemic regarding education practices remote / online / distance created based on legislation that allowed face-to-face classes to be replaced by distance activities

Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise

During submaximal exercise fatty acids are a predominant energy source for muscle contractions. An important regulator of fatty acid oxidation is acetyl‐CoA carboxylase (ACC), which exists as two isoforms (ACC1 and ACC2) with ACC2 predominating in skeletal muscle. Both ACC isoforms regulate malonyl‐CoA production, an allosteric inhibitor of carnitine palmitoyltransferase 1 (CPT‐1); the primary enzyme controlling fatty acyl‐CoA flux into mitochondria for oxidation. AMP‐activated protein kinase (AMPK) is a sensor of cellular energy status that is activated during exercise or by pharmacological agents such as metformin and AICAR. In resting muscle the activation of AMPK with AICAR leads to increased phosphorylation of ACC (S79 on ACC1 and S221 on ACC2), which reduces ACC activity and malonyl‐CoA; effects associated with increased fatty acid oxidation. However, whether this pathway is vital for regulating skeletal muscle fatty acid oxidation during conditions of increased metabolic flux such as exercise/muscle contractions remains unknown. To examine this we characterized mice lacking AMPK phosphorylation sites on ACC2 (S212 in mice/S221 in humans‐ACC2‐knock‐in [ACC2‐KI]) or both ACC1 (S79) and ACC2 (S212) (ACC double knock‐in [ACCD‐KI]) during submaximal treadmill exercise and/or ex vivo muscle contractions. We find that surprisingly, ACC2‐KI mice had normal exercise capacity and whole‐body fatty acid oxidation during treadmill running despite elevated muscle ACC2 activity and malonyl‐CoA. Similar results were observed in ACCD‐KI mice. Fatty acid oxidation was also maintained in muscles from ACC2‐KI mice contracted ex vivo. These findings indicate that pathways independent of ACC phosphorylation are important for regulating skeletal muscle fatty acid oxidation during exercise/muscle contractions

The Role of the Partner of an Entrepreneur

This research examines the role of one’s partner in the motivation of the entrepreneur in the small and medium enterprise. This impact has been analyzed in terms of the hierarchy of needs as explained in the Theory of Human Motivation by Abraham Maslow (1991). The study uses a qualitative analysis of twenty-two cases of entrepreneurs who have had partners in the initial or growth stage of the company, and who have up to fifteen years in the market and that sell less than fifteen million dollars annually. The results of the study show that the motivation of the partner seems to be a factor that is valued and recognized by the entrepreneurs, and the entrepreneurs of both genders acknowledge the moral support of their partners as one of the major factor in the development and growth of their businesses. Among its practical implications, the research provides a theoretical framework for understanding the motivational role of the partners and the entrepreneurs and establishes that entrepreneurs who have managed to stay in the activity of the new business with the support of the partner seem to be perceived as successful people. The originality and value of this study is that it provides primary information on the relationship between the businessperson and his/her partner and contributes to the understanding of the role of partners in the development of the business activities of an entrepreneur

2015 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp

2018 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus

Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer’s Disease using structural MR and FDG-PET images

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1–3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature