Early regional hypometabolism in presymptomatic MAPT carriers : a GENFI sub-study

Presqu’un tier des cas de démence frontotemporale est causé par une mutation sur les gènes progranulin (GRN), microtubule-associated protein tau (MAPT) ou chromosome 9 open reading frame 72 (C9ORF72). Plusieurs années avant le début de la maladie, plusieurs études montrent déjà des changements au niveau cérébral chez les porteurs présymptomatiques de ces mutations. En utilisant la TEP-FDG, nous posons l’hypothèse que les changements cérébraux de ces porteurs de mutations apparaîtront de façon plus précoce qu’en utilisant des techniques d’imagerie traditionnelles. Nous avons recruté 18 participants venant de familles à risque de DFT (6 porteurs de mutations MAPT et 12 nonporteurs) de l’étude GENFI. Un examen clinique et neuropsychologique complet a été effectué. Une TEP-FDG a été effectuée chez tous nos participants. Les images ont été segmentées et analysées par le logiciel MIMNeuro. Les porteurs et non-porteurs ne diffèrent pas significativement entre les groupes quant au métabolisme cérébral peu importe la région. L’évaluation visuelle par un médecin nucléiste expert ne semble pas non-plus être en mesure de différencier les porteurs des non-porteurs. L’observation qualitative des imageries des patients semble montrer des altérations médiales temporales chez la majorité des porteurs de mutation et chez quelques non-porteurs.About one third of frontotemporal dementia (FTD) are caused by mutations on the progranulin (GRN), microtubule-associated protein tau (MAPT) or chromosome 9 open reading frame 72 (C9ORF72) genes. Several studies show that there are cerebral changes many years prior to the actual onset of the disease in pre-symptomatic carriers. Using fluorodeoxyglucose-positron emission tomography (FDG-PET), we expected to observe cerebral changes in carriers earlier than other traditional imaging techniques. We recruited 18 participants from families at risk of FTD (6 carriers and 12 non-carriers) from the GENFI study. A complete clinical and neuropsychological examination was performed. FDG-PET scan was done in all participants. Carriers and non-carriers did not differ significantly regarding brain metabolism (regardless of the region). Visual inspection by an expert nuclear medicine specialist could not differentiate carriers from non-carriers. Qualitative analyses of imaging of patients showed medial temporal alterations in most carriers and in some noncarriers

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. HIGHLIGHTS: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors

BACKGROUND: PAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements. RESULTS: Due to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1. CONCLUSION: Our data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair

A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk

Background This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations. Aims This review and summary of the conference focus on four key areas related to the biology of dairy foods and fats and their potential impact on human health: (a) the effect of dairy foods on CVD in prospective cohort studies; (b) the impact of dairy fat on plasma lipid risk factors for CVD; (c) the effects of dairy fat on non-lipid risk factors for CVD; and (d) the role of dairy products as essential contributors of micronutrients in reference food patterns for the elderly. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD. Thus, recommendations to reduce dairy food consumption irrespective of the nature of the dairy product should be made with cautionJ. Bruce German, Robert A. Gibson, Ronald M. Krauss, Paul Nestel, Benoît Lamarche, Wija A. van Staveren, Jan M. Steijns, Lisette C. P. G. M. de Groot, Adam L. Lock and Frédéric Destaillat

L’échec de la fiction

Luís Gustavo Ãlvarez RuedaRector Beatriz Toloza SuárezVicerrectora Académica Leonardo Porras MartínezVicerrector Administrativo y Financiero William Guerrero SalazarDirector Departamento de Investigación  EQUIPO EDITORIALIng. Faver Adrián Amorocho SepúlvedaDecano Facultad de Ciencias Naturales e IngenieríaUNISANGIL M.Sc. Sandra Johana Benítez MuñozEditora C. S-P. Laura Lida Sánchez MartínezCoordinadora de Publicaciones  COMITÉ EDITORIALEsp. Wilson Gamboa ContrerasDirector Grupo de Innovación y Desarrollo Tecnológico de Unisangil - Identus M.Sc. Frank Carlos Vargas TanguaDirector Grupo de Estudios Ambientales para la Sostenibilidad, la Innovación y el Desarrollo, Geasid, UNISANGIL Esp. Henry Javier Barón GonzálezDirector Grupo de estudios avanzados en tecnologías de información y comunicaciones de UNISANGIL - Hydra Ing. Milton Javier Muñoz NeiraDirector Programa Ingeniería Electrónica,UNISANGIL Ing. Enrique Blanco OlarteDirector Programa Ingeniería de MantenimientoUNISANGIL Esp. Edgar Rodríguez DíazDirector Programa Ingeniería AgrícolaUNISANGILIng. Yaneyda Zulay Longas FlórezDirectora Programa Ingeniería de SistemasUNISANGIL Ing. Diana Patricia Torres SolanoDirectora Programa Ingeniería AmbientalUNISANGIL Expedito Archila TrianaDirector Programa Tecnología en SistemasUNISANGIL Ing. Ana Lucía Hurtado MesaDirectora Programa Ingeniería de SistemasUNISANGIL Sede Chiquinquirá Ing. Wilson Arturo Gómez BecerraDirector Programa Ingeniería Electrónica,UNISANGIL Sede Yopal Ing. Erika Sofía Cely GranadosDirectora Programa Ingeniería de SistemasUNISANGIL Sede Yopal Ing. Tatiana Maribel Mahecha ÃngelDirectora Ingeniería AmbientalUNISANGIL Sede Yopal Ing. Lucelly Martínez TrochezDirectora Programa Ingeniería AgrícolaUNISANGIL Sede Yopal  COMITÉ CIENTÃFICOM.Sc. Mayerly Juliana Aparicio QuiñonezCandidato a PhD en Química de MaterialesM.Sc. en Catálisis y ProcesosIngeniera Química Ph.D. Ariel René Carreño OlejuaProfesor asociado e investigadorFacultad de Ingeniería MecánicaUniversidad Pontificia Bolivariana UPB Seccional Bucaramanga M.Sc. Miguel René Mogollón LancherosCandidato a PhD en Ciencias de la AgriculturaM.Sc. en Ingeniería agrícolaIngeniero AgrícolaAsesor Instituto Geográfico Agustín Codazzi - IGAC M.Sc. Héctor Iván Gómez OrtizCandidato a PhD en Ingeniería (Ing. Eléctrica, Electrónica y Gestión & Desarrollo)M.Sc. en CienciasIng. ElectrónicoUniversidad Industrial de Santander  ÃRBITROSDiana Patricia Torres SolanoEspecialista en Química AmbientalIngeniera AmbientalUNISANGIL Yuleimy Ramírez OrdoñezJoven Investigadora ColcienciasIngeniera Ambiental Gerardo Correa PamplonaGestor Empresarial – Ingeniero AmbientalCoordinador de Calidad y Laboratorios Jorge Luis Cornejo PlataIngeniero Electrónico, UPBDocente programas Ingeniería Electrónica,Ingeniería de Mantenimiento Gustavo Adolfo Gómez GómezIngeniero de SistemasDesarrollador Web y Arquitecto de Software Manuel Fernando Lizarazo BallesterosIngeniero en SistemasIngeniero de Proyectos y Docente Catedra Néstor Jesús Páez SarmientoCandidato a M.Sc. en Informática educativaEspecialista en Gerencia InformáticaIngeniero de SistemasDocente, UNISANGIL  TRADUCCIÓNInstituto de Idiomas UNISANGIL REVISIÓN LINGÃœÃSTICAC. S-P. Diana Lucía Díaz PatiñoARTE Y DIAGRAMACIÓNFutura Diseño e Impresión Â

Effects of short-term normobaric hypoxia on haematology, muscle phenotypes and physical performance in highly trained athletes

This study aimed to determine the impact of short-term normobaric hypoxia on physiology and performance in highly trained athletes. Twelve (7 male and 5 female) athletes were randomly assigned into two groups and spent 8 h per night for two consecutive nights a week over 3 weeks under either short-term normobaric hypoxia (simulating 3636 m altitude, inspired O2= 13%) or in normobaric normoxia in a single-blind study. Following a 3 week washout period, athletes were then exposed to the other condition. Athletes were tested for maximal oxygen consumption and time to exhaustion on an electromagnetically braked cycle ergometer before and after each treatment in addition to being tested for anaerobic performance (Wingate test) on a modified Monark cycle ergometer. Blood samples were taken throughout the experiment and vastus lateralis muscle biopsies were taken before and after each treatment. Increases in red blood cell count, haematocrit, haemoglobin, platelet number and erythropoietin concentration were observed following short-term normobaric hypoxia. Except for a modest decrease in phosphofructokinase activity following short-term normobaric hypoxia, no changes were observed in muscle enzyme activities, buffer capacity, capillary density or morphology. No performance measures were changed following short-term normobaric hypoxia or normobaric normoxia. Although short-term normobaric hypoxia exposure increased levels of a number of haematological parameters, this was not associated with improved aerobic or anaerobic performance in highly trained athletes

How do modifiable risk factors affect Alzheimer's disease pathology or mitigate its effect on clinical symptom expression?

Epidemiological studies show that modifiable risk factors account for about 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (sAD). Recent findings suggest that these factors might also modify disease trajectories of people with autosomal dominant Alzheimer's disease (ADAD). With positron emission tomography (PET) imaging it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former "resistance pathway" suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the "resilience pathway" suggests that modifiable risk factors might mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and might appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sAD and ADAD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions

ComputeCanada/magic_castle: Magic Castle 12.6.3

<p>No changes to infrastructure code.</p> <p>Refer to <a href="https://github.com/ComputeCanada/puppet-magic_castle/blob/main/CHANGELOG.md">puppet-magic_castle changelog</a></p&gt