Clinical presentation and early evolution of spastic ataxia of Charlevoix-Saguenay.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an increasingly recognized form of spastic ataxia worldwide, but early diagnosis remains a challenge.

Methods: We reviewed the initial presentation (n = 40) and early clinical evolution (n = 50) of a large ARSACS cohort that was followed at the Saguenay Neuromuscular clinic.

Results: The average age at presentation was 3.

Widespread distribution of soluble di-iron monooxygenase (SDIMO) genes in Arctic groundwater impacted by 1,4-dioxane.

Soluble di-iron monooxygenases (SDIMOs), especially group-5 SDIMOs (i.e., tetrahydrofuran and propane monooxygenases), are of significant interest due to their potential role in the initiation of 1,4-dioxane (dioxane) degradation.

Hypoxia induces re-entry of committed cells into pluripotency.

Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self-renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC- or iPSC-derived differentiated cells back to a stem cell-like state, as evidenced by re-activation of an Oct4-promoter reporter.

Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

The lethal toxin (LT) of Bacillus anthracis, composed of the protective antigen (PA) and the lethal factor (LF), plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF) to form the edema toxin (ET), which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF.

Regulation of stem cell populations by microRNAs.

miRNAs are small non-coding RNAs that have emerged as crucial post-transcriptional regulators of gene expression. They are key players in various critical cellular processes such as proliferation, cell cycle progression, apoptosis and differentiation. Self-renewal capacity and differentiation potential are hallmarks of stem cells.

Copper deficiency leads to anemia, duodenal hypoxia, upregulation of HIF-2α and altered expression of iron absorption genes in mice.

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes.

[Prevalence survey of cardiovascular risk factors in the general population in St. Louis (Senegal)].

Background: Cardiovascular diseases are becoming with their risk factors a real health problem in Africa. The objectives of this study were to assess the prevalence of risk factors for cardiovascular diseases in the general population in Saint-Louis, Senegal.

Methodology: This is a cross-sectional, descriptive and analytical made in May 2010, in the Senegalese aged 15, residing in the city of Saint-Louis, Senegal.

Isolation of antibodies from non-human primates for clinical use.

Antibodies intended for clinical use have been isolated from non-human primates (NHP), chimpanzees (Pan troglodytes) and macaques (Macaca fascicularis and Macaca mulatta), essentially with the use of the phage-display technology. All studies presenting such isolations have been reviewed and presented here, following the main steps of this technology, and advantages and disadvantages of NHP species were analyzed. Optimization of the tolerance of chimeric NHP-human antibodies by germline humanization was mentioned, and the recent alleviation of legal constraints was revealed.

In vivo three-dimensional kinematics of the cervical spine during maximal axial rotation.

The cervical spine exhibits considerable mobility, especially in axial rotation. Axial rotation exerts stress on anatomical structures, such as the vertebral artery which is commonly assessed during clinical examination. The literature is rather sparse concerning the in vivo three-dimensional segmental kinematics of the cervical spine.

Nonhost resistance of tomato to the bean pathogen Pseudomonas syringae pv. syringae B728a is due to a defective E3 ubiquitin ligase domain in avrptobb728a.

The bean pathogen Pseudomonas syringae pv. syringae B728a expresses homologs of the type III effectors AvrPto and AvrPtoB, either of which can trigger resistance in tomato cultivars expressing Pto and Prf genes. We found that strain B728a also elicits nonhost resistance in tomato cultivars VFNT Cherry and Moneymaker that lack Pto but express other members of the Pto family (e.

Diversity of ARSACS mutations in French-Canadians.

Background: The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability.

Methods: Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause.

Prevalence of lifestyle risk factors in myotonic dystrophy type 1.

Background: The prevalence of unhealthy lifestyle habits such as smoking has seldom been described in neuromuscular disorders, including myotonic dystrophy type 1 (DM1). However, it is essential to document the unhealthy lifestyle habits as they can exacerbate existing impairments and disabilities. The objectives are: 1) To determine the prevalence of risk factors among individuals with DM1; 2) To compare the prevalence among classic and mild phenotypes.

C9orf72 hexanucleotide repeat expansions as the causative mutation for chromosome 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia.

Objective: To further assess the presence of a large hexanucleotide repeat expansion in the first intron of the C9orf72 gene identified as the genetic cause of chromosome 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) in 4 unrelated families with a conclusive linkage to c9ALS/FTD.

Design: A repeat-primed polymerase chain reaction assay.

Setting: Academic research.

Argonaute proteins couple chromatin silencing to alternative splicing.

Argonaute proteins play a major part in transcriptional gene silencing in many organisms, but their role in the nucleus of somatic mammalian cells remains elusive. Here, we have immunopurified human Argonaute-1 and Argonaute-2 (AGO1 and AGO2) chromatin-embedded proteins and found them associated with chromatin modifiers and, notably, with splicing factors. Using the CD44 gene as a model, we show that AGO1 and AGO2 facilitate spliceosome recruitment and modulate RNA polymerase II elongation rate, thereby affecting alternative splicing.

Both lethal and edema toxins of Bacillus anthracis disrupt the human dendritic cell chemokine network.

Bacillus anthracis, the agent of anthrax, produces two main virulence factors: a capsule and two toxins. Both lethal toxin (LT) and edema toxin (ET) paralyze the immune defense system. Here, we analyze the effects of LT and ET on the capacity of human monocyte-derived dendritic cells (MoDC) to produce proinflammatory chemokines.

Epidemiological surveillance of myotonic dystrophy type 1: a 25-year population-based study.

This epidemiological study investigates the evolution of the prevalence and the phenotypes in a large cohort of myotonic dystrophy type 1 (DM1) patients living in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) over a 25-year period (1985-2010). In 1985, 406 patients with DM1 were known. From 1985 to 2010, 352 new DM1 patients were diagnosed and 321 patients died.

[Screening for asymptomatic peripheral arterial occlusive disease of the lower limbs by measuring the ankle-brachial index in the general population (Senegal)].

Objectives: The purpose of this study was to investigate the prevalence of peripheral arterial disease (PAOD) and cardiovascular risk factors associated with the ankle-brachial index (ABI) in Senegalese patients aged 40 years and over.

Methodology: We prospectively studied a random sample of Senegalese aged 40 years and older, residing in the city of St.-Louis, Senegal.

Plant preference for ammonium versus nitrate: a neglected determinant of ecosystem functioning?

Although nitrogen (N) availability is a major determinant of ecosystem properties, little is known about the ecological importance of plants' preference for ammonium versus nitrate (β) for ecosystem functioning and the structure of communities. We modeled this preference for two contrasting ecosystems and showed that β significantly affects ecosystem properties such as biomass, productivity, and N losses. A particular intermediate value of β maximizes the primary productivity and minimizes mineral N losses.

Defense mechanisms of Pseudomonas aeruginosa PAO1 against quantum dots and their released heavy metals.

The growing use of quantum dots (QDs) in numerous applications increases the possibility of their release to the environment. Bacteria provide critical ecosystem services, and understanding their response to QDs is important to assess the potential environmental impacts of such releases. Here, we analyze the microbial response to sublethal exposure to commercial QDs, and investigate potential defense and adaptation mechanisms in the model bacterium Pseudomonas aeruginosa PAO1.

Understanding and estimating the power to detect cross-level interaction effects in multilevel modeling.

Cross-level interaction effects lie at the heart of multilevel contingency and interactionism theories. Researchers have often lamented the difficulty of finding hypothesized cross-level interactions, and to date there has been no means by which the statistical power of such tests can be evaluated. We develop such a method and report results of a large-scale simulation study, verify its accuracy, and provide evidence regarding the relative importance of factors that affect the power to detect cross-level interactions.

Efficacy and tolerability of a 20-mg dose of methylphenidate for the treatment of daytime sleepiness in adult patients with myotonic dystrophy type 1: a 2-center, randomized, double-blind, placebo-controlled, 3-week crossover trial.

Background: Despite the fact that excessive daytime sleepiness (EDS) is one of the most common manifestations in patients with myotonic dystrophy type 1 (DM1), no treatment is yet available. Methylphenidate is being studied for prospective use in the treatment of EDS.

Objective: The aim of this investigator-initiated study was to evaluate the efficacy and tolerability of a single 20-mg morning dose of methylphenidate for the treatment of EDS in adults with DM1.

Vitamin D status among 4-month-old infants in New England: a prospective cohort study.

Background: Concerns over vitamin D deficiency in infants and children recently prompted the American Academy of Pediatrics to recommend increased supplementation. Few studies have examined vitamin D status in the same infants over time. Also, while many researchers label "breastfeeding" as a risk factor for vitamin D deficiency, few differentiate between any breastfeeding, exclusive breastfeeding, and supplemented or unsupplemented breastfeeders.

Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans.

An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues.

Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase.

7-Ketocholesterol (7KC) is a cytotoxic oxysterol that plays a role in many age-related degenerative diseases. 7KC formation and accumulation often occurs in the lysosome, which hinders enzymatic transformations that reduce its toxicity and increase the sensitivity to lysosomal membrane permeabilization. We assayed the potential to mitigate 7KC cytotoxicity and enhance cell viability by overexpressing 7KC-active enzymes in human fibroblasts.