ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg

In the endoplasmic reticulum (ER) of eukaryotes, N-linked glycans are first assembled on the lipid carrier dolichyl pyrophosphate. The GlcNAc2Man9Glc3 oligosaccharide is transferred to selected asparagine residues of nascent polypeptides. Defects along the biosynthetic pathway of N-glycans are associated with severe multisystemic syndromes called congenital disorders of glycosylation. Here, we describe a deficiency in the ALG12 ER α1,6-mannosyltransferase resulting in a novel type of glycosylation disorder. The severe disease was identified in a child presenting with psychomotor retardation, hypotonia, growth retardation, dysmorphic features and anorexia. In the patient's fibroblasts, the biosynthetic intermediate GlcNAc2Man7 oligosaccharide was detected both on the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins, thus pointing to a defect in the dolichyl pyrophosphate-GlcNAc2Man7-dependent ALG12 α1,6 mannosyltransferase. Analysis of the ALG12 cDNA in the CDG patient revealed compound heterozygosity for two point mutations that resulted in the amino acid substitutions T67M and R146Q, respectively. The impact of these mutations on ALG12 protein function was investigated in the Saccharomyces cerevisiae alg12 glycosylation mutant by showing that the yeast ALG12 gene bearing the homologous mutations T61M and R161Q and the human mutant ALG12 cDNA alleles failed to normalize the growth defect phenotype of the alg12 yeast model, whereas expression of the normal ALG12 cDNA complemented the yeast mutation. The ALG12 mannosyltransferase defect defines a new type of congenital disorder of glycosylation, designated CDG-I

Fragmentation Functions for Lepton Pairs

We calculate the fragmentation function for a light quark to decay into a lepton pair to leading order in the QCD coupling constant. In the formal definition of the fragmentation function, a QED phase must be included in the eikonal factor to guarantee QED gauge invariance. We find that the longitudinal polarization fraction is a decreasing function of the factorization scale, in accord with the intuitive expectation that the virtual photon should behave more and more like a real photon as the transverse momomentum of the fragmenting quark increases.Comment: 13 pages, 4 figures, normalization corrected, text abbreviate

Phase Referencing in Optical Interferometry

One of the aims of next generation optical interferometric instrumentation is to be able to make use of information contained in the visibility phase to construct high dynamic range images. Radio and optical interferometry are at the two extremes of phase corruption by the atmosphere. While in radio it is possible to obtain calibrated phases for the science objects, in the optical this is currently not possible. Instead, optical interferometry has relied on closure phase techniques to produce images. Such techniques allow only to achieve modest dynamic ranges. However, with high contrast objects, for faint targets or when structure detail is needed, phase referencing techniques as used in radio interferometry, should theoretically achieve higher dynamic ranges for the same number of telescopes. Our approach is not to provide evidence either for or against the hypothesis that phase referenced imaging gives better dynamic range than closure phase imaging. Instead we wish to explore the potential of this technique for future optical interferometry and also because image reconstruction in the optical using phase referencing techniques has only been performed with limited success. We have generated simulated, noisy, complex visibility data, analogous to the signal produced in radio interferometers, using the VLTI as a template. We proceeded with image reconstruction using the radio image reconstruction algorithms contained in AIPS IMAGR (CLEAN algorithm). Our results show that image reconstruction is successful in most of our science cases, yielding images with a 4 milliarcsecond resolution in K band. (abridged)Comment: 11 pages, 36 figure

Antiplatelet Therapy and Platelet Function Testing

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58558/1/20370_ftp.pd

Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik

Defects of N-linked glycosylation represent diseases with multiple organ involvements that are classified as congenital disorders of glycosylation (CDG). In recent years, several CDG types have been attributed to defects of dolichol-linked oligosaccharide assembly in the endoplasmic reticulum. The profiling of [3H]mannose-labeled lipid-linked oligosaccharides was instrumental in identifying most of these glycosylation disorders. However, this method is poorly suited for the identification of short lipid-linked oligosaccharide biosynthesis defects. To adequately resolve deficiencies affecting the first steps of lipid-linked oligosaccharide formation, we have used a non-radioactive procedure employing the fluorescence detection of 2-aminobenzamide-coupled oligosaccharides after HPLC separation. By applying this method, we have detected the accumulation of dolichylpyrophosphate-GlcNAc2 in a previously untyped CDG patient. The accumulation pattern suggested a deficiency of the ALG1 β1,4 mannosyltransferase, which adds the first mannose residue to lipid-linked oligosaccharides. This was supported by the finding that this CDG patient was compound heterozygous for three mutations in the ALG1 gene, leading to the amino acid substitutions S150R and D429E on one allele and S258L on the other. The detrimental effect of these mutations on ALG1 protein function was demonstrated in a complementation assay using alg1 Saccharomyces cerevisiae yeast mutants. The ALG1 mannosyltransferase defect described here represents a novel type of CDG, which should be referred to as CDG-I

Kentucky Labor Supply and Demand Surveys

Excerpt from the executive summary: The Center for Business and Economic Research at the University of Kentucky (CBER), along with its partners, the Survey Research Center at the University of Kentucky (UK-SRC), the Survey Research Center in the Urban Studies Institute at the University of Louisville (UL-SRC), and the Department of Economics at the University of Louisville, is pleased to present this final report on the findings of the Kentucky labor supply and demand surveys sponsored by the Kentucky Cabinet for Workforce Development. The two universities have put together a consortium including some of the best scholars in the region in the areas of labor economics, local economic development, and survey design and administration

B Production Asymmetries in Perturbative QCD

This paper explores a new mechanism for B production in which a b quark combines with a light parton from the hard-scattering process before hadronizing into the B hadron. This recombination mechanism can be calculated within perturbative QCD up to a few nonperturbative constants. Though suppressed at large transverse momentum by a factor Lambda_QCD m_b/p_t^2 relative to b quark fragmentation production, it can be important at large rapidities. A signature for this heavy-quark recombination mechanism in proton-antiproton colliders is the presence of rapidity asymmetries in B cross sections. Given reasonable assumptions about the size of nonperturbative parameters entering the calculation, we find that the asymmetries are only significant for rapidities larger than those currently probed by collider experiments.Comment: 17 pages, LaTeX, 4 ps figures, tightenlines, sections added, final version accepted for publication in Phys. Rev.

" Développer une nouvelle approche pédagogique ", questionnement autour du cas de PicoLibre

International audienceCe papier s'intéresse à la problématique de mise en place d'une démarche pédagogique innovante dans le cadre des technologies de l'information et de la communication (TIC). Le sujet de cette analyse est une expérience qui a commencé voilà 2 à 3 ans au GET (Groupe des Ecoles des Télécommunication). Au terme de cette période, nous pointons un certain nombre d'observations et de réflexions par rapport à notre démarche même