2,3,4-Triacet­oxy-1-[5-(1,2,3,4-tetra­acetoxy­butyl)pyrazin-2-yl]butyl acetate

The title compound, C28H36N2O16, was obtained unintentionally in an attempt to synthesize 1,3,4,6-tetra-O-acetyl-2-azido-2-de­oxy-d-mannopyran­ose. The crystal packing utilizes methyl–acet­oxy C—H⋯O and meth­yl–pyrazine C—H⋯N hydrogen bonding

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery

OBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized num-bers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impair-ment. METHODS The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of >= 10 points. Two prospective registries in Swit- zerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS In the development (2437 patients, 48.2% male; mean age +/- SD: 55 +/- 15 years) and external validation (2427 patients, 42.4% male; mean age +/- SD: 58 +/- 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, al- though machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Microbial shifts in the aging mouse gut

YesBackground: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice. Results: The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis. Conclusion: We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.This work was supported by the Canadian Institutes of Health Research (CIHR) through an Emerging Team Grant to RGB, CIHR Operating Grants to Langille et al. Microbiome 2014, 2:50 Page 10 of 12 http://www.microbiomejournal.com/content/2/1/50 SEH (MOP 126018) and RAR (MOP 93718), and a CIHR Fellowship to MGIL. Infrastructure was supported by the Canada Foundation for Innovation through a grant to RGB. RGB also acknowledges the support of the Canada Research Chairs program

Biological Action of Phosphonate Analogs of Fructose 2,6-Bisphosphate on Enzymes from Higher-Plants

AbstractTwo analogs of fructose 2,6-bisphosphate have been prepared, in which the phosphoryl group on the second carbon is replaced by a methylphosphonoyl or a phosphonoyl group. Both inhibited spinach leaf cytosolic fructose-1,6-bisphosphatase and activated potato tuber pyrophosphate:fructose-6-phosphate phosphotransferase. Their relative effectiveness depended on the enzyme, revealing differences in the fructose 2,6-bisphosphate binding sites on the two enzymes. Their relative effectiveness and their binding constants were the same when pyrophosphate:fructose-6-phosphate phosphotransferase was assayed in the forward and in the reverse direction. It is concluded that pyrophosphate:fructose-6-phosphate phosphotransferase possesses one type of fructose 2,6-bisphosphate binding site, and catalysis is modified in parallel in both directions as the activator concentration is altered. These results led to the reinterpretation of the role of pyrophosphate:fructose-6-phosphate phosphotransferase and fructose 2,6-bisphosphate in higher plants

Probing specific lectin-carbohydrate interactions using atomic force microscopy imaging and force measurements

Knowledge of the molecular interactions between lectins and carbohydrates is a key to understand cellular interactions and to develop new bioanalytical applications. We have used atomic force microscopy (AFM) imaging and force measurements to probe the specific interactions between the lectin concanavalin A (Con A) and oligoglucose saccharides. To this end, gold-coated substrates were first functionalized with Con A and thiol-terminated hexasaccharide molecules. The functionalization procedures were validated by means of X-ray photoelectron spectroscopy and AFM. AFM images recorded in aqueous solution revealed that the hexasaccharide-terminated substrates interact specifically with the lectin. Force-distance curves were then recorded between hexasaccharide-terminated AFM probes and Con A-terminated substrates. About half of the retraction curves showed unbinding forces of 96 +/- 55 pN (n = 100), along with elongation forces and rupture lengths ranging from 0 to 200 nm. These features were not observed when the measurements were performed in the presence of mannose or with a hydroxyl-terminated probe. These results, together with the AFM images, indicate that the measured unbinding forces originate from specific lectin-carbohydrate interactions. The carbohydrate AFM probes designed here offer promising prospects for mapping lectin receptors at cell surfaces