Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration

Mutations in SIGMAR1, which encodes the Sigma 1 receptor, cause a familial form of amyotrophic lateral sclerosis, but the underlying molecular mechanisms are unclear. Bernard-Marissal et al. reveal that disruption of Sigma 1 receptor function disturbs endoplasmic reticulum-mitochondria interactions and functions, resulting in degeneration specifically of motor neuron

Normative Values of Bone Mineral Content and Bone Mineral Density Assessed by Double X-ray Absorptiometry in Congolese Urban Women

Introduction: The World Health Organization (WHO) have validated dual X-ray absorptiometry as the “gold standard” densitometric technique for assessing Bone Mineral Density (BMD) and Bone Mineral Content (BMC).The definitions of osteopenia and osteoporosis are based on its results Loss of bone mass with ageing or osteoprosis leads to decline of bone strength and fragility fractures. There are racial/ethnic differences in bone mass parameters for populations of different ethnic origins although living in the same environmental. WHO criteria for the diagnosis of osteoporosis and the associated risks of fractures are based on bone parameters assessed by dual x absorptiometry in postmenopausal Caucasian women. Studies have shown the necessity to establish reference data for bone mass measurements for each population according to habit and ethnicity.These data are lacking for Congolese populations. This study aims to establish spine and hip normative values in healthy Congolese women population and to compare them with those for Caucasian, Asian, and others ethnical groups. Materials and methods: 604 bantus women aged from 18 to 92 years were recruited after public media advertising and undergoes DXA of spine and hip. To be included in the study, women must fulfill the conditions of absence of factor affecting bone metabolism. Results: Bone mass parameters shows a growth up to the peak that is reached in the fourth decade followed by a slow decay that causes a loss of nearly 14.2% in BMD and BMC over a period of 20 years and, then a decrease more pronounced towards the sixtieth year (1.5% yearly), higher than among Caucasians Asians and Arabs. We found that the references curves for the lumbar spine and total hip are significantly differences from the Caucasian, Asean or Arab. Conclusion: Spine and hip normatives values of BMD and BMC of Congolese urban women was etablished and were different to those of compared populations

Expression of mitofusin 2R94Q in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A

Charcot-Marie-Tooth disease type 2A is an autosomal dominant axonal form of peripheral neuropathy caused by mutations in the mitofusin 2 gene. Mitofusin 2 encodes a mitochondrial outer membrane protein that participates in mitochondrial fusion in mammalian cells. How mutations in this protein lead to Charcot-Marie-Tooth disease type 2A pathophysiology remains unclear. We have generated a transgenic mouse expressing either a mutated (R94Q) or wild-type form of human mitofusin 2 in neurons to evaluate whether the R94Q mutation was sufficient for inducing a Charcot-Marie-Tooth disease type 2A phenotype. Only mice expressing mitofusin 2R94Q developed locomotor impairments and gait defects thus mimicking the Charcot-Marie-Tooth disease type 2A neuropathy. In these animals, the number of mitochondria per axon was significantly increased in the distal part of the sciatic nerve axons with a diameter smaller than 3.5 μm. Importantly, the analysis of R94Q transgenic animals also revealed an age-related shift in the size of myelinated axons leading to an over-representation of axons smaller than 3.5 μm. Together these data suggest a link between an increased number of mitochondria in axons and a shift in axonal size distribution in mitofusin 2R94Q transgenic animals that may contribute to their neurological phenotyp

Ultrasound Assessment of Bone Mass in Central Africans Population

Background: Osteodensitometry, a procedure increasingly accepted by clinicians to access osteoporosis is not yet fully validated by WHO. It requires the establishment of normal values and references curves for each population, and in our community, this is not yet assessed.The purpose of this study was twofold: to describe the profile of the speed of sound of proximal phalangeal metaphysis and establish references curves in central Africans and to compare them with those of other populations specially Caucasians.Methods: This cross sectional study was carried out at Kinshasa, Democratic Republic of the Congo in Central Africa from January to December 2016.Four hundred twenty four subjects aged from 20 to 87 years old, were explored and the speed of sound in theirs proximal phalanges measured using ultrasound equipment. Age, gender, hormonal status and speed of sound were collected and analyzed.Results: The mean value of the Amplitude Dependent Speed of Sound (AD-SoS) showed a growth feature with age (from 2056 m/sec at second decade of life to 2145.27 m/sec at fourth decade followed by a progressive decrease which was present in both sexes but more marked in postmenopausal women (1927.06 m/sec). This mean value was higher than in Caucasian studies. In this study, age and hormonal status seems to be the bone quality most influencing anthropometric factors as seen in many series.The curve profile with age was also a polynomial curve as seen in others populations of the world.Conclusion: This study provides normal data for phalangeal ultrasound measurements and reference curve of central Africans which were compared to those of Western studies

PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

Summary: The sensation of pain is essential for the preservation of the functional integrity of the body. However, the key molecular regulators necessary for the initiation of the development of pain-sensing neurons have remained largely unknown. Here, we report that, in mice, inactivation of the transcriptional regulator PRDM12, which is essential for pain perception in humans, results in a complete absence of the nociceptive lineage, while proprioceptive and touch-sensitive neurons remain. Mechanistically, our data reveal that PRDM12 is required for initiation of neurogenesis and activation of a cascade of downstream pro-neuronal transcription factors, including NEUROD1, BRN3A, and ISL1, in the nociceptive lineage while it represses alternative fates other than nociceptors in progenitor cells. Our results thus demonstrate that PRDM12 is necessary for the generation of the entire lineage of pain-initiating neurons. : The sensation of pain, temperature, and itch by neurons of the nociceptive lineage is essential for animal survival. Bartesaghi et al. report that the transcriptional regulator PRDM12 is indispensable in neural crest cells (NCCs) for the initiation of the sensory neuronal differentiation program that generates the entire nociceptive lineage. Keywords: neurogenesis, pain, nociceptive neurons, Prdm12, neural crest cell

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cell

Global Transcriptional Programs in Peripheral Nerve Endoneurium and DRG Are Resistant to the Onset of Type 1 Diabetic Neuropathy in Ins2Akita/+ Mice

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2Akita/+ mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2Akita/+ and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2Akita/+ mice and sex-matched littermate controls. Our phenotypic analysis of Ins2Akita/+ mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM

Introduction d'un logiciel de simulation d'algorithmes dans le processus enseignement apprentissage de l'algorithmique chez les apprenants débutants de l'ENSET de Libreville

International audienceThis article is a reflection from our project of doctoral thesis through which we try to verify whether the introduction of ICT tools, here an application of simulation algorithms (called " Algobox "), in the teaching-learning algorithms among learners can improve the effectiveness of the teaching-learning process. The objective of this research is to provide some solution to the problem of high failure rate found by the administrative and educational leaders for several years in the teaching of algorithmic at the ENSET of LibrevilleCet article qui présente notre projet de thèse est une première approche visant à faire la présentation d'une tentative d'introduction des TICE, en l'occurrence une application de simulation d'algorithme (Algobox) dans le processus enseignement-apprentissage de l'algorithmique chez des apprenants débutants. L'utilisation de ce logiciel vise pour objectif de proposer une contribution au problème du fort taux d'échec constaté par les respon-sables administratifs et pédagogiques depuis plusieurs années dans l'enseignement de l'algorithmique à l'ENSET de Libreville

Introduction d'un logiciel de simulation d'algorithmes dans le processus enseignement apprentissage de l'algorithmique chez les apprenants débutants de l'ENSET de Libreville

International audienceThis article is a reflection from our project of doctoral thesis through which we try to verify whether the introduction of ICT tools, here an application of simulation algorithms (called " Algobox "), in the teaching-learning algorithms among learners can improve the effectiveness of the teaching-learning process. The objective of this research is to provide some solution to the problem of high failure rate found by the administrative and educational leaders for several years in the teaching of algorithmic at the ENSET of LibrevilleCet article qui présente notre projet de thèse est une première approche visant à faire la présentation d'une tentative d'introduction des TICE, en l'occurrence une application de simulation d'algorithme (Algobox) dans le processus enseignement-apprentissage de l'algorithmique chez des apprenants débutants. L'utilisation de ce logiciel vise pour objectif de proposer une contribution au problème du fort taux d'échec constaté par les respon-sables administratifs et pédagogiques depuis plusieurs années dans l'enseignement de l'algorithmique à l'ENSET de Libreville