Adverse events following pandemic A (H1N1) 2009 monovalent vaccines in pregnant women--Taiwan, November 2009-August 2010

Background

During the 2009 H1N1 pandemic, pregnant women were prioritized to receive the unadjuvanted or MF59®-adjuvanted pandemic A (H1N1) 2009 monovalent vaccines (“2009 H1N1 vaccines”) in Taiwan regardless of stage of pregnancy. Monitoring adverse events following 2009 H1N1 vaccination in pregnant women was a priority for the mass immunization campaign beginning November 2009.

Methods/Findings

We characterized reports to the national passive surveillance from November 2009 through August 2010 involving adverse events following 2009 H1N1 vaccines among pregnant women. Reports from the passive surveillance were matched to a large-linked database on a unique identifier, date of vaccination, and date of diagnosis in a capture-recapture analysis to estimate the true number of spontaneous abortion after 2009 H1N1 vaccination. We verified 16 spontaneous abortions, 11 stillbirths, 4 neonatal deaths, 4 nonpregnancy-specific adverse events, and 2 inadvertent immunizations in recipients who were unaware of pregnancy at time of vaccination. The Chapman capture-recapture estimator of true number of spontaneous abortion after 2009 H1N1 vaccination was 329 (95% confidence interval [CI] 196–553). Of the 14,474 pregnant women who received the 2009 H1N1 vaccines, the estimated risk of spontaneous abortion was 2.3 (95% CI, 1.4–3.8) per 100 pregnancies, compared with a local background rate of 12.8 (95% CI, 12.8–12.9) per 100 pregnancies.

Conclusions

The passive surveillance provided rapid initial assessment of adverse events after 2009 H1N1 vaccination among pregnant women. Its findings were reassuring for the safety of 2009 H1N1 vaccines in pregnancy.     

Cloning, expression, and characterization of a new xylanase from alkalophilic Paenibacillus sp. 12-11

A xylanase gene, xyn7c, was cloned from Paenibacillus sp. 12-11, an alkalophilic strain isolated from the alkaline wastewater sludge of a paper mill, and expressed in Escherichia coli. The full-length gene consists of 1,296 bp and encodes a mature protein of 400 residues (excluding the putative signal peptide) that belongs to the glycoside hydrolase family 10. The optimal pH of the purified recombinant XYN7C was found to be 8.0, and the enzyme had good pH adaptability at 6.5-8.5 and stability over a broad pH range of 5.0-11.0. XYN7C exhibited maximum activity at 55 degrees C and was thermostable at 50 degrees C and below. Using wheat arabinoxylan as the substrate, XYN7C had a high specific activity of 1,886 U/mg, and the apparent Km and Vmax values were 1.18 mg/ml and 1,961 μmol/mg/min, respectively. XYN7C also had substrate specificity towards various xylans, and was highly resistant to neutral proteases. The main hydrolysis products of xylans were xylose and xylobiose. These properties make XYN7C a promising candidate to be used in biobleaching, baking, and cotton scouring processes.     

Contributions of A2A and A2B adenosine receptors in coronary flow responses in relation to the KATP channel using A2B and A2A/2B double-knockout mice

Adenosine plays a role in physiological and pathological conditions, and A(2) adenosine receptor (AR) expression is modified in many cardiovascular disorders. In this study, we elucidated the role of the A(2B)AR and its relationship to the A(2A)AR in coronary flow (CF) changes using A(2B) single-knockout (KO) and A(2A/2B) double-KO (DKO) mice in a Langendorff setup. We used two approaches: 1) selective and nonselective AR agonists and antagonists and 2) A(2A)KO and A(2B)KO and A(2A/2B)DKO mice. BAY 60-6583 (a selective A(2B) agonist) had no effect on CF in A(2B)KO mice, whereas it significantly increased CF in wild-type (WT) mice (maximum of 23.3 ± 9 ml·min(-1)·g(-1)). 5'-N-ethylcarboxamido adenosine (NECA; a nonselective AR agonist) increased CF in A(2B)KO mice (maximum of 34.6 ± 4.7 ml·min(-1)·g(-1)) to a significantly higher degree compared with WT mice (maximum of 23.1 ± 2.1 ml·min(-1)·g(-1)). Also, CGS-21680 (a selective A(2A) agonist) increased CF in A(2B)KO mice (maximum of 29 ± 1.9 ml·min(-1)·g(-1)) to a significantly higher degree compared with WT mice (maximum of 25.1 ± 2.3 ml·min(-1)·g(-1)). SCH-58261 (an A(2A)-selective antagonist) inhibited the NECA-induced increase in CF to a significantly higher degree in A(2B)KO mice (19.3 ± 1.6 vs. 0.5 ± 0.4 ml·min(-1)·g(-1)) compared with WT mice (19 ± 3.5 vs. 3.6 ± 0.5 ml·min(-1)·g(-1)). NECA did not induce any increase in CF in A(2A/2B)DKO mice, whereas a significant increase was observed in WT mice (maximum of 23.1 ± 2.1 ml·min(-1)·g(-1)). Furthermore, the mitochondrial ATP-sensitive K(+) (K(ATP)) channel blocker 5-hydroxydecanoate had no effect on the NECA-induced increase in CF in WT mice, whereas the NECA-induced increase in CF in WT (17.6 ± 2 ml·min(-1)·g(-1)), A(2A)KO (12.5 ± 2.3 ml·min(-1)·g(-1)), and A(2B)KO (16.2 ± 0.8 ml·min(-1)·g(-1)) mice was significantly blunted by the K(ATP) channel blocker glibenclamide (to 0.7 ± 0.7, 2.3 ± 1.1, and 0.9 ± 0.4 ml·min(-1)·g(-1), respectively). Also, the CGS-21680-induced (22 ± 2.3 ml·min(-1)·g(-1)) and BAY 60-6583-induced (16.4 ± 1.60 ml·min(-1)·g(-1)) increase in CF in WT mice was significantly blunted by glibenclamide (to 1.2 ± 0.4 and 1.8 ± 1.2 ml·min(-1)·g(-1), respectively). In conclusion, this is the first evidence supporting the compensatory upregulation of A(2A)ARs in A(2B)KO mice and demonstrates that both A(2A)ARs and A(2B)ARs induce CF changes through K(ATP) channels. These results identify AR-mediated CF responses that may lead to better therapeutic approaches for the treatment of cardiovascular disorders.     

Widespread gamma-secretase activity in the cell, but do we need it at the mitochondria?

gamma-Secretase cleavage of the amyloid precursor protein already subjected to a prior beta-secretase cleavage generates beta-amyloid (Abeta) peptide fragments, which are major constituents of the amyloid plagues found in Alzheimer's disease brain tissues. gamma-Secretase activity and components of the gamma-secretase complex are found in the endoplasmic reticulum-Golgi intermediate compartment, the Golgi, the trans-Golgi network, the plasma membrane, the endosomal-lysosomal system and recently, the mitochondria. Abeta fragments have been shown to be neurotoxic, leading to mitochondrial dysfunction and enhanced apoptotic cell death. However, if Abeta fragments are indeed detrimental to neurons, the widespread presence of enzymatic activity that would result in their generation in the cell appears to make little sense. The presence of a gamma-secretase complex in the mitochondrion, an organelle that is particularly susceptible to Abeta toxicity, is even more puzzling. Emerging evidence suggests that both secreted and intracellular Abeta fragments have endogenous functions. Also, while the fibrillogenic Abeta1-42 is clearly neurotoxic, the more abundant and soluble Abeta1-40 is an antioxidant and could potentially be neuroprotective in several ways. A "physiological" amount of Abeta1-40 production by cellular gamma-secretase activity may be part of the neuron's natural counter against oxidative damage, in addition to endogenous roles in neuronal survival and modulation of synaptic transmission. In any case, whether Abeta is produced locally in the mitochondria and the function for mitochondrial Abeta, if produced, is yet unclear.     

Biochemical genetic markers in the Kadazans of Sabah,Malaysia

Summary Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C₅, group specific component, haptoglobin and transferrin.Kadazans were found to be polymorphic for GLOI, PGMI, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C₅, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK.     

Vinyl Chloride Monomer (VCM) Induces High Occurrence of Neural Tube Defects in Embryonic Mouse Brain During Neurulation

The aim of this study was to explore the direct embryonic teratogenicity of vinyl chloride monomer (VCM), especially the toxic effects on the early development of the nervous system and its underlying mechanisms. Pregnant mice at embryonic day 6.5 (E6.5) were injected with different doses of VCM (200, 400 and 600 mg/kg) and embryos were harvested at E10.5. Our results showed that doses higher than 400 mg/kg of VCM increased the incidence of malformed embryos, especially the neural tube defects (NTDs). In addition, high-dose of VCM decreased mitotic figure counts in the neuroepithelium and enhanced the percentage of cells in G0/G1 phase, while they were reduced in S phase. The more VCM was injected into mice, the fewer positive PCNA cells were seen and the more positive TUNEL cells were observed in the neuroepithelium. Moreover, significant increases in the levels of caspase-3 protein were observed in NTD embryos. Our results demonstrate that during early pregnancy, exposure to doses higher than 400 mg/kg of VCM increases the incidence of malformations and particularly the rate of NTDs. High-dose of VCM inhibits the proliferation of neural cells and induces cell apoptosis, leading to an imbalance in the ratio of proliferation and apoptosis. Meanwhile, the apoptosis of neuroepithelial cells might be accelerated by the activation of the caspase-3 pathway, and it might be a reason for NTDs.     

Alpine grassland plants grow earlier and faster but biomass remains unchanged over 35 years of climate change

Satellite data indicate significant advancement in alpine spring phenology over decades of climate warming, but corresponding field evidence is scarce. It is also unknown whether this advancement results from an earlier shift of phenological events, or enhancement of plant growth under unchanged phenological pattern. By analyzing a 35‐year dataset of seasonal biomass dynamics of a Tibetan alpine grassland, we show that climate change promoted both earlier phenology and faster growth, without changing annual biomass production. Biomass production increased in spring due to a warming‐induced earlier onset of plant growth, but decreased in autumn due mainly to increased water stress. Plants grew faster but the fast‐growing period shortened during the mid‐growing season. These findings provide the first in situ evidence of long‐term changes in growth patterns in alpine grassland plant communities, and suggest that earlier phenology and faster growth will jointly contribute to plant growth in a warming climate.