ObjectiveMeningococcal meningitis is a public health burden. Immunization strategies have reduced global incidence of the disease. Glycoconjugate vaccines are the most effective type of vaccine to combat most causes of meningococcal meningitis. These vaccines contain capsular polysaccharide fragments from disease-causing serogroups of Neisseria meningitidis that are chemically attached to a carrier protein. The enzymes responsible for capsular polysaccharide synthesis can serve as tools to make these critical vaccine components. One such enzyme is the N. meningitidis serogroup W capsule polymerase. This enzyme is responsible for creating the galactose-sialic acid containing capsular polysaccharide of this serogroup. Our aim in this study was to determine the binding affinities of nucleotide sugar donors CMP-sialic acid and UDP-galactose using a coupled transferase assay to inform future work to modulate polysaccharide synthesis by this enzyme.ResultsWe determined a Km of 66.8 µM for CMP-sialic acid and a Km for UDP-galactose of 3.9 µM. These values are lower than reported values for other retaining galactosyltransferases and inverting sialyltransferases respectively. There were difficulties obtaining reliable data for galactosyltransferase activity. An alternate strategy is needed to assess kinetic parameters of the separate transferase activities for this enzyme.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3596-y) contains supplementary material, which is available to authorized users.
To better understand the endocrine mechanisms that underlie sexually dimorphic growth (females grow faster) in yellow perch (Perca flavescens), real-time quantitative polymerase chain reaction (qPCR) was used to measure pituitary, liver, and ovary mRNA levels of genes related to growth and reproduction-sex in this species. Adult perch were collected from Lake Erie and body mass, age, gonadosomatic index (I (G)), hepatosomatic index (I (H)), and gene expression for growth hormone (GH), prolactin, somatolactin, insulin-like growth factor Ib (IGF-Ib), estrogen receptor alpha (esr1), estrogen receptor betaa (esr2a), and aromatase (cyp19a1a) were measured. Females had higher body mass, I (H), and liver esr1 mRNA level than males, while males had higher liver IGF-Ib, liver esr2a, and liver cyp19a1a mRNA levels. In both sexes, season had a significant effect on GH and liver IGF-Ib mRNAs with higher levels occurring in spring, which also corresponded with higher liver cyp19a1a mRNA levels. For females, I (G), liver esr1, and ovary cyp19a1a mRNA levels were higher in autumn than the spring, and ovary cyp19a1a mRNA levels showed a significant negative correlation with pituitary GH and liver IGF-Ib mRNA levels. The most significant (p = 0.001) relationships across the parameters measured were positive correlations between liver IGF-Ib and esr2a mRNA levels and liver IGF-Ib and cyp19a1a mRNA levels. This study shows significant effects of season and sex on adult yellow perch endocrine physiology.
Introduction: Tenecteplase has been demonstrated to be an effective option for thrombolysis in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Thrombolysis decision making is an important component of telestroke consultations. Data is scarce concerning tenecteplase usage in telestroke patients. We aimed to evaluate if tenecteplase was safe and feasible for patients with confirmed LVO in a large telestroke network. Methods: We conducted a retrospective analysis of AIS patients with LVO and treated with thrombolysis from May 2018 to April 2021. We compared outcomes in telestroke patients treated with IV alteplase (May 2018 - April 2020) to patients treated with IV tenecteplase (May 2020 - April 2021). We evaluated our primary efficacy and safety outcomes: 90 day functional outcome as measured by modified Rankin Scale (mRS) and complications related to thrombolysis. Secondary outcomes included door to needle time (DTN) and door in door out time (DIO). Ordinal regression assessed 90 day mRS and binomial logistic regression analysis evaluated complications between the groups. Quantile regression models assessed the median to compared groups for DTN and DIO. Results: There were 3747 telestroke consults during the study period and 537 (14.3%) were found to have an LVO, of which 109 (39 IV tenecteplase; 70 IV alteplase) were eligible, received thrombolysis and were included in this study. Patients treated with IV tenecteplase had significantly less disability at 90 days compared to patients treated with IV alteplase [1 (0 - 4.5) vs. 3 (1 - 6)], adjusted odds ratio (aOR) = 0.31 [95%CI, 0.14 - 0.72], p = 0.006, based on mRS ordinal shift analysis. Similar complication rates were reported between the thrombolysis groups, aOR = 3.73 [95%CI, 0.23 - 59.95], p = 0.35. An adjusted quantile regression model found IV tenecteplase was administered 9.40 minutes quicker, standard error (SE) = 3.67, [95%CI, 2.11 - 16.69] than IV alteplase, p = 0.01. There were no differences reported between thrombolysis groups and DIO, p = 0.63. Conclusion: Telestroke patients presenting with confirmed LVO and treated with IV tenecteplase were found to have better 90 day outcomes compared to patients treated with IV alteplase, without increased complication rates.
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