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Belgium & Luxembourg
Lonely Planet's Belgium & Luxembourg is your passport to the most relevant, up-to-date advice on what to see and skip, and what hidden discoveries await you. Explore Unesco-listed belfries in Bruges and Tournai, savour Belgian pralines at a Brussels chocolatier and stroll along the river gorge in Luxembourg City - all with your trusted travel companion. Get to the heart of Belgium & Luxembourg and begin your journey now!
Book
Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia
It remains an enigma whether gestational hypertension (GH) and pre-eclampsia (PE) are distinct entities or different spectrum of the same disease. We aimed to compare the risk factors and outcomes between GH and PE.
A total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the analysis. Cox proportional hazards model was used to identify and compare the risk factors for GH and PE by treating gestational age at delivery as the survival time. Logistic regression model was used to compare outcome. Subgroup analysis was performed for early- and late-onset PE.
GH and PE shared most risk factors including overweight and obesity, nulliparity, PE history, type 1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs. RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed substantial difference. Risk factors modified gestational age at delivery in patients with GH and PE in similar pattern. Subgroup analysis showed that early- and late-onset PE shared some risk factors with different effect sizes, whereas folic acid supplementation showed protective effect for early-onset PE only. PE was strongly associated with several adverse outcomes including cesarean section, placental abruption, small for gestational age, preterm birth, and 5 min Apgar score < 7, whereas GH was associated with increased risk of preterm birth only.
GH and PE shared common risk factors. Differences in effect sizes of risk factors and outcomes indicate that the conditions may have different pathophysiology and mechanism.
Journal Article
Pathogenesis, epidemiology and control of Group A Streptococcus infection
Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.In this Review, Brouwer et al. summarize recent developments in our understanding of Group A Streptococcus (GAS), focusing on the epidemiologic and clinical features of GAS infection and the molecular mechanisms associated with GAS virulence and drug resistance.
Journal Article
Avengers arena : the complete collection
\"Trapped on an isolated island, sixteen superhuman teens -- including members of the Runaways and Avengers Academy -- are given a chilling ultimatum by their demented captor. And only one of them will make it out alive! Thus begins a primal battle that tests each combatant's skills, stamina, and morals. Welcome to Arcade's Murderworld -- where secrets are plenty, alliances are fleeting, and the key to victory might be rewriting the rules of the game\"--Page [4] of cover.
Book
Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis
To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain.
Journal Article
Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family
Background
Lanthipeptides belong to the ribosomally synthesized and post-translationally modified peptide group of natural products and have a variety of biological activities ranging from antibiotics to antinociceptives. These peptides are cyclized through thioether crosslinks and can bear other secondary post-translational modifications. While lanthipeptide biosynthetic gene clusters can be identified by the presence of genes encoding characteristic enzymes involved in the post-translational modification process, locating the precursor peptides encoded within these clusters is challenging due to their short length and high sequence variability, which limits the high-throughput exploration of lanthipeptide biosynthesis. To address this challenge, we enhanced the predictive capabilities of Rapid ORF Description & Evaluation Online (RODEO) to identify members of all four known classes of lanthipeptides.
Results
Using RODEO, we mined over 100,000 bacterial and archaeal genomes in the RefSeq database. We identified nearly 8500 lanthipeptide precursor peptides. These precursor peptides were identified in a broad range of bacterial phyla as well as the Euryarchaeota phylum of archaea. Bacteroidetes were found to encode a large number of these biosynthetic gene clusters, despite making up a relatively small portion of the genomes in this dataset. A number of these precursor peptides are similar to those of previously characterized lanthipeptides, but even more were not, including potential antibiotics. One such new antimicrobial lanthipeptide was purified and characterized. Additionally, examination of the biosynthetic gene clusters revealed that enzymes installing secondary post-translational modifications are more widespread than initially thought.
Conclusion
Lanthipeptide biosynthetic gene clusters are more widely distributed and the precursor peptides encoded within these clusters are more diverse than previously appreciated, demonstrating that the lanthipeptide sequence-function space remains largely underexplored.
Journal Article
Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB
Structural and biochemical studies show that the biosynthesis of the food preservative nisin involves the tRNA-dependent glutamylation of serine and threonine.
Mechanisms of lantibiotic biosynthesis
Nisin, a member of the lantibiotic family of thioether-bridge containing antibiotics, has been used widely in the food industry for more than 40 years without substantial development of resistance. This property has become of particular interest in light of the emergence of resistance to many clinically used antibiotics. Wilfred van der Donk and colleagues present the X-ray structure of the lantibiotic dehydratase NisB, an enzyme involved in nisin biosynthesis, and use biochemical data to show that NisB utilizes glutamyl-tRNA
Glu
in the critical activation of Ser/Thr residues. These findings provide a basis for the functional characterization of the many lantibiotic-like dehydratases involved in the biosynthesis of other classes of natural products.
Lantibiotics are a class of peptide antibiotics that contain one or more thioether bonds. The lantibiotic nisin is an antimicrobial peptide that is widely used as a food preservative to combat food-borne pathogens
1
. Nisin contains dehydroalanine and dehydrobutyrine residues that are formed by the dehydration of Ser/Thr by the lantibiotic dehydratase NisB (ref.
2
). Recent biochemical studies revealed that NisB glutamylates Ser/Thr side chains as part of the dehydration process
3
. However, the molecular mechanism by which NisB uses glutamate to catalyse dehydration remains unresolved. Here we show that this process involves glutamyl-tRNA
Glu
to activate Ser/Thr residues. In addition, the 2.9-Å crystal structure of NisB in complex with its substrate peptide NisA reveals the presence of two separate domains that catalyse the Ser/Thr glutamylation and glutamate elimination steps. The co-crystal structure also provides insights into substrate recognition by lantibiotic dehydratases. Our findings demonstrate an unexpected role for aminoacyl-tRNA in the formation of dehydroamino acids in lantibiotics, and serve as a basis for the functional characterization of the many lantibiotic-like dehydratases involved in the biosynthesis of other classes of natural products.
Journal Article
Streptococcal superantigens and the return of scarlet fever
Streptococcus pyogenes (group A Streptococcus ) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators. Although scarlet fever had largely declined in both prevalence and severity since the late 19th century, outbreaks have now reemerged in multiple geographical regions over the past decade. Here, we review recent findings that address the role of superantigens in promoting a fitness advantage for S . pyogenes within human populations and discuss how superantigens may be suitable targets for vaccination strategies.
Journal Article