The Aquaporin Gene Family of the Yellow Fever Mosquito, Aedes aegypti

The mosquito, Aedes aegypti, is the principal vector of the Dengue and yellow fever viruses. During feeding, an adult female can take up more than its own body weight in vertebrate blood. After a blood meal females excrete large amounts of urine through their excretion system, the Malpighian tubules (MT). Diuresis starts within seconds after the mosquito starts feeding. Aquaporins (AQPs) are a family of membrane transporters that regulate the flow of water, glycerol and other small molecules across cellular membranes in both prokaryotic and eukaryotic cells. Our aim was to identify aquaporins that function as water channels, mediating transcellular water transport in MTs of adult female Ae. aegypti.Using a bioinformatics approach we screened genome databases and identified six putative AQPs in the genome of Ae. aegypti. Phylogenetic analysis showed that five of the six Ae. aegypti AQPs have high similarity to classical water-transporting AQPs of vertebrates. Using microarray, reverse transcription and real time PCR analysis we found that all six AQPs are expressed in distinct patterns in mosquito tissues/body parts. AaAQP1, 4, and 5 are strongly expressed in the adult female MT. RNAi-mediated knockdown of the MT-expressed mosquito AQPs resulted in significantly reduced diuresis.Our results support the notion that AQP1, 4, and 5 function as water transporters in the MTs of adult female Ae. aegypti mosquitoes. Our results demonstrate the importance of these AQPs for mosquito diuresis after blood ingestion and highlight their potential as targets for the development of novel vector control strategies

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

<p>Abstract</p> <p>Background</p> <p>Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as <it>bidi </it>and <it>rokok daun </it>are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.</p> <p>Methods</p> <p>Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.</p> <p>Results</p> <p>Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).</p> <p>Conclusions</p> <p>Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.</p

Chemical genetics strategies for identification of molecular targets

Chemical genetics is an emerging field that can be used to study the interactions of chemical compounds, including natural products, with proteins. Usually, the identification of molecular targets is the starting point for studying a drug’s mechanism of action and this has been a crucial step in understanding many biological processes. While a great variety of target identification methods have been developed over the last several years, there are still many bioactive compounds whose target proteins have not yet been revealed because no routine protocols can be adopted. This review contains information concerning the most relevant principles of chemical genetics with special emphasis on the different genomic and proteomic approaches used in forward chemical genetics to identify the molecular targets of the bioactive compounds, the advantages and disadvantages of each and a detailed list of successful examples of molecular targets identified with these approaches

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

How sulphate-reducing microorganisms cope with stress: lessons from systems biology

Sulphate-reducing microorganisms (SRMs) are a phylogenetically diverse group of anaerobes encompassing distinct physiologies with a broad ecological distribution. As SRMs have important roles in the biogeochemical cycling of carbon, nitrogen, sulphur and various metals, an understanding of how these organisms respond to environmental stresses is of fundamental and practical importance. In this Review, we highlight recent applications of systems biology tools in studying the stress responses of SRMs, particularly Desulfovibrio spp., at the cell, population, community and ecosystem levels. The syntrophic lifestyle of SRMs is also discussed, with a focus on system-level analyses of adaptive mechanisms. Such information is important for understanding the microbiology of the global sulphur cycle and for developing biotechnological applications of SRMs for environmental remediation, energy production, biocorrosion control, wastewater treatment and mineral recovery