N-glycoside neoglycotrimers from 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide

2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl azide is available on large scale from D-glucose by means of a three-step sequence involving acetylation, activation as the glycosyl bromide, and stereospecific displacement with azide anion. The azide functionality then serves as a convenient anchor upon which to introduce new functionality, usually with retention of the beta-stereochemistry. Here we report the synthesis of an amide-linked N-glycosyl trimer, by employing a Staudinger-aza-Wittig process on the azide, as well as a hybrid N-glycosyl triazole-amide-linked trimer in which the sugars are separated by 1,2,3-triazole heterocycles. Both of these neoglycotrimers are isolated in good yield with high beta-selectivity in each case.     

Retroviral MDR1 gene transfer into marrow-engrafting human peripheral blood progenitor cells results in preferential transgene expression in the immature myeloid compartment rather than in mature myeloid progeny in vivo

BACKGROUND: The objective of multidrug resistance-1 (MDR1) gene therapy is protection of the myeloid cell lineage. It is therefore important to examine the effect of retroviral transduction on myeloid maturation. Transfer of the human MDR1 gene can confer resistance to a variety of cytostatic drugs. For a safe application in humans it is paramount to follow-up the development of transduced cells. METHODS: We transduced human mobilized peripheral blood progenitor cells (PBPC) with a viral vector containing the human MDR1 cDNA and transplanted the transduced cells into non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. The progeny of the transduced cells was analyzed in detail by flow cytometry. RESULTS: A detailed analysis by four-color flow cytometry showed that MDR1 transgene-expressing CD33+ myeloid cells were preferentially negative for the maturation-associated myeloid markers CD11b and CD10, while the untransduced CD33+ myeloid cells expressed significantly higher proportions of these Ag (P<0.01 each). There was no difference in the expression of B- or T-lymphoid Ag among the MDR1-transduced and untransduced lymphoid cells. DISCUSSION: These data indicate that retroviral MDR1 gene transfer results in preferential P-glycoprotein expression in myeloid progenitor cells, which is the target cell population for myelotoxicity of cytostatic drugs.     

A new powdery mildew resistance allele at the Pm4 wheat locus transferred from einkorn (Triticum monococcum)

Powdery mildew is one of the most destructive foliar diseases of wheat. A set of differential Blumeria graminis f.sp. tritici (Bgt) isolates was used to test the powdery mildew response of a Triticum monococcum-derived resistant hexaploid line, Tm27d2. Segregation analysis of 95 F_2:3 lines from a Chinese Spring/Tm27d2 cross revealed that the resistance of Tm27d2 is controlled by a single dominant gene. Using monosomic analysis and a molecular mapping approach, the resistance gene was localized to the terminal end of chromosome 2AL. The linkage map of chromosome 2AL consisted of nine simple sequence repeat markers and one sequence-tagged site (STS) marker (ResPm4) indicative for the Pm4 locus. According to the differential reactions of 19 wheat cultivars/lines with known powdery mildew resistance genes to 13 Bgt isolates, Tm27d2 carried a new resistance specificity. The complete association of the resistance allele with STS marker ResPm4 indicated that it represented a new allele at the Pm4 locus. This new allele was designated Pm4d. The two flanking markers Xgwm526 and Xbarc122 closely linked to Pm4d at genetic distances of 3.4 and 1.0 cM, respectively, are present in chromosome bin 2AL1-0.85-1.00.     

Excitability decreasing central motor plasticity is retained in multiple sclerosis patients

ABSTRACT: BACKGROUND: Compensation of brain injury in multiple sclerosis (MS) may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-)acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1) in force control in patients with MS. METHODS: We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP) in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. RESULTS: cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 +/- 22 % of baseline amplitude, p < 0.001) and in MS patients (69 +/- 18 %, p < 0.001). In contrast, post-cTBS force production performance was only impaired in controls (2.2 +/- 2.8, p = 0.011), but not in MS patients (2.0 +/- 4.4, p = 0.108). The decline in force production performance following cTBS correlated with corticomuscular latencies (CML) in MS patients, but did not correlate with MEP amplitude reduction in patients or controls. CONCLUSIONS: Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion-induction by cTBS.     

Small effective population sizes in two planktonic freshwater copepod species (Eudiaptomus) with apparently large census sizes

In small planktonic organisms, large census sizes (N(c)) suggest large effective population sizes (N(e)), but reliable estimates are rare. Here, we present N(e)/N(c) ratios for two freshwater copepod species (Eudiaptomus sp.) using temporal samples of multilocus microsatellite genotypes and a pseudo-likelihood approach. N(e)/N(c) ratios were very small in both Eudiaptomus species (10(-7)-10(-8)). Although we hypothesized that the species producing resting eggs (E. graciloides) had a larger N(e) than the other (E. gracilis), estimates were not statistically different (E. graciloides: N(e) = 672.7, CI: 276-1949; E. gracilis: N(e) = 1027.4, CI: 449-2495), suggesting that the propagule bank of E. graciloides had no detectable influence on N(e).     

Le BNP dans l’exploration de l’insuffisance cardiaque et le syndrome coronarien aigu

Le BNP, ou “Brain Natriuretic Peptide”, initialement mis en évidence au niveau de l’encéphale de porc, est aujourd’hui renommé “B-type natriuretic peptide” en raison de l’origine myocardique chez l’homme. Sa synthèse, principalement réalisée au niveau du ventricule gauche, à partir d’une pro-hormone, le Pro-BNP, est liée à l’état d’étirement de la paroi ventriculaire.     

The merrit alloantigenic system of human B lymphocytes: evidence for thirteen possible factors including one six-member segregant series.

An analysis of the typing results of a 70-member chronic lymphatic leukemia B cell panel revealed evidence for 13 possible groups of the Merrit alloantigenic system. Six of these appeared possibly allelic and may represent a segregant series. The CLL panel was also fully typed for HLA and some degree of linkage dysequilibrium between Merrit and HLA seemed apparent from the data. Merrit antibodies can be absorbed out with selected surface membrane immunoglobulin (SMIG)-positive normal lymphocytes and less so or not at all with E rosette-forming T cells or Fc-positive SMIG-negative lymphocytes.