The fitness of African malaria vectors in the presence and limitation of host behaviour

<p>Background Host responses are important sources of selection upon the host species range of ectoparasites and phytophagous insects. However little is known about the role of host responses in defining the host species range of malaria vectors. This study aimed to estimate the relative importance of host behaviour to the feeding success and fitness of African malaria vectors, and assess its ability to predict their known host species preferences in nature.</p> <p>Methods Paired evaluations of the feeding success and fitness of African vectors Anopheles arabiensis and Anopheles gambiae s.s in the presence and limitation of host behaviour were conducted in a semi-field system (SFS) at Ifakara Health Institute, Tanzania. In one set of trials, mosquitoes were released within the SFS and allowed to forage overnight on a host that was free to exhibit natural behaviour in response to insect biting. In the other, mosquitoes were allowed to feed directly on from the skin surface of immobile hosts. The feeding success and subsequent fitness of vectors under these conditions were investigated on 6 host types (humans, calves, chickens, cows, dogs and goats) to assess whether physical movements of preferred host species (cattle for An. arabiensis, humans for An. gambiae s.s.) were less effective at preventing mosquito bites than those of common alternatives.</p> <p>Results Anopheles arabiensis generally had greater feeding success when applied directly to host skin than when foraging on unrestricted hosts (in five of six host species). However, An. gambiae s.s obtained blood meals from free and restrained hosts with similar success from most host types (four out of six). Overall, the blood meal size, oviposition rate, fecundity and post-feeding survival of mosquito vectors were significantly higher after feeding on hosts free to exhibit behaviour, than those who were immobilized during feeding trials.</p> <p>Conclusions Allowing hosts to move freely during exposure to mosquitoes was associated with moderate reductions in mosquito feeding success, but no detrimental impact to the subsequent fitness of mosquitoes that were able to feed upon them. This suggests that physical defensive behaviours exhibited by common host species including humans do not impose substantial fitness costs on African malaria vectors.</p&gt

Identification of a tyrosine residue responsible for N-acetylimidazole-induced increase of activity of ecto-nucleoside triphosphate diphosphohydrolase 3

Chemical modification in combination with site-directed mutagenesis was used to identify a tyrosine residue responsible for the increase in ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) nucleotidase activity after acetylation with a tyrosine-selective reagent, N-acetylimidazole. The NTPDase3 ATPase activity is increased more than the ADPase activity by this reagent. Several fairly well conserved tyrosine residues (252, 255, and 262) that are located in or very near apyrase conserved region 4a (ACR4a) were mutated. These mutants were all active, but mutation of tyrosine 252 to either alanine or phenylalanine eliminated the activity increase observed after N-acetylimidazole treatment of the wild-type enzyme. This suggests that the acetylation of tyrosine 252 is responsible for the increased activity. Stabilization of quaternary structure has resulted in increased enzyme activities for the NTPDases. However, mutation of these three tyrosine residues did not result in global changes of tertiary or quaternary structure, as measured by Cibacron blue binding, chemical cross linking, and native gel electrophoretic analysis. Nevertheless, disruption of the oligomeric structure with the detergent Triton X-100 abolished the increase in activity induced by this reagent. In addition, mutations that abolished the N-acetylimidazole effect also attenuated the increases of enzyme activity observed after lectin and chemical cross-linking treatments, which were previously attributed to stabilization of the quaternary structure. Thus, we speculate that the acetylation of tyrosine 252 might induce a subtle conformational change in NTPDase3, resulting in the observed increase in activity

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well’ population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of d13 660 and d18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well’ population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population

Aggressive fibromatosis of the head and neck: a new classification based on a literature review over 40 years (1968-2008)

BACKGROUND: Fibromatosis is an aggressive fibrous tumor of unknown etiology that is, in some cases, lethal. Until now, there has been no particular classification for the head and neck. Therefore, the aim of the present study was to review the current literature in order to propose a new classification for future studies. METHODS: An evidence-based literature review was conducted from the last 40 years regarding aggressive fibromatosis in the head and neck. Studies that summarized patients' data without including individual data were excluded. RESULTS: Between 1968 and 2008, 179 cases with aggressive fibromatosis of the head and neck were published. The male to female ratio was 91 to 82 with a mean age of 16.87 years, and 57.32% of the described cases that involved the head and neck were found in patients under 11 years. The most common localization was the mandible, followed by the neck. All together, 143 patients were followed up, and in 43 (30.07%), a recurrence was seen. CONCLUSION: No clear prognostic factors for recurrence (age, sex, or localization) were observed. A new classification with regard to hormone receptors and bone involvement could improve the understanding of risk factors and thereby assist in future studies

Regulatory Effect of Connexin 43 on Basal Ca2+ Signaling in Rat Ventricular Myocytes

Background: It has been found that gap junction-associated intracellular Ca 2+ [Ca 2+]i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca 2+ signaling, in particular the basal [Ca 2+] i activities, is unclear. Methods and Results: Global and local Ca 2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs) and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY), respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43) with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca 2+ transients and local Ca 2+ sparks in monolayer NRVMs and Ca 2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP3 butyryloxymethyl ester) and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca 2+ signal and LY uptake by gap uncouplers, whereas blockade of IP 3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca 2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibod

An empirical approach to selecting community-based alcohol interventions:combining research evidence, rural community views and professional opinion

<p>Abstract</p> <p>Background</p> <p>Given limited research evidence for community-based alcohol interventions, this study examines the intervention preferences of rural communities and alcohol professionals, and factors that influence their choices.</p> <p>Method</p> <p>Community preferences were identified by a survey of randomly selected individuals across 20 regional Australian communities. The preferences of alcohol professionals were identified by a survey of randomly selected members of the Australasian Professional Society on Alcohol and Other Drugs. To identify preferred interventions and the extent of support for them, a budget allocation exercise was embedded in both surveys, asking respondents to allocate a given budget to different interventions. Tobit regression models were estimated to identify the characteristics that explain differences in intervention preferences.</p> <p>Results</p> <p>Community respondents selected school programs most often (88.0%) and allocated it the largest proportion of funds, followed by promotion of safer drinking (71.3%), community programs (61.4%) and police enforcement of alcohol laws (60.4%). Professionals selected GP training most often (61.0%) and allocated it the largest proportion of funds, followed by school programs (36.6%), community programs (33.8%) and promotion of safer drinking (31.7%). Community views were susceptible to response bias. There were no significant predictors of professionals' preferences.</p> <p>Conclusions</p> <p>In the absence of sufficient research evidence for effective community-based alcohol interventions, rural communities and professionals both strongly support school programs, promotion of safer drinking and community programs. Rural communities also supported police enforcement of alcohol laws and professionals supported GP training. The impact of a combination of these strategies needs to be rigorously evaluated.</p

RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation

Design of a randomized controlled trial of physical training and cancer (Phys-Can) – the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome

Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Methods/design: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 × 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression. Discussion: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated

Vector-Virus Mutualism Accelerates Population Increase of an Invasive Whitefly

The relationships between plant viruses, their herbivore vectors and host plants can be beneficial, neutral, or antagonistic, depending on the species involved. This variation in relationships may affect the process of biological invasion and the displacement of indigenous species by invaders when the invasive and indigenous organisms occur with niche overlap but differ in the interactions. The notorious invasive B biotype of the whitefly complex Bemisia tabaci entered China in the late 1990s and is now the predominant or only biotype in many regions of the country. Tobacco curly shoot virus (TbCSV) and Tomato yellow leaf curl China virus (TYLCCNV) are two whitefly-transmitted begomoviruses that have become widespread recently in south China. We compared the performance of the invasive B and indigenous ZHJ1 whitefly biotypes on healthy, TbCSV-infected and TYLCCNV-infected tobacco plants. Compared to its performance on healthy plants, the invasive B biotype increased its fecundity and longevity by 12 and 6 fold when feeding on TbCSV-infected plants, and by 18 and 7 fold when feeding on TYLCCNV-infected plants. Population density of the B biotype on TbCSV- and TYLCCNV-infected plants reached 2 and 13 times that on healthy plants respectively in 56 days. In contrast, the indigenous ZHJ1 performed similarly on healthy and virus-infected plants. Virus-infection status of the whiteflies per se of both biotypes showed limited effects on performance of vectors on cotton, a nonhost plant of the viruses. The indirect mutualism between the B biotype whitefly and these viruses via their host plants, and the apparent lack of such mutualism for the indigenous whitefly, may contribute to the ability of the B whitefly biotype to invade, the displacement of indigenous whiteflies, and the disease pandemics of the viruses associated with this vector

Discerning natural and anthropogenic organic matter inputs to salt marsh sediments of Ria Formosa lagoon (South Portugal)

Sedimentary organic matter (OM) origin and molecular composition provide useful information to understand carbon cycling in coastal wetlands. Core sediments from threors' Contributionse transects along Ria Formosa lagoon intertidal zone were analysed using analytical pyrolysis (Py-GC/MS) to determine composition, distribution and origin of sedimentary OM. The distribution of alkyl compounds (alkanes, alkanoic acids and alkan-2-ones), polycyclic aromatic hydrocarbons (PAHs), lignin-derived methoxyphenols, linear alkylbenzenes (LABs), steranes and hopanes indicated OM inputs to the intertidal environment from natural-autochthonous and allochthonous-as well as anthropogenic. Several n-alkane geochemical indices used to assess the distribution of main OM sources (terrestrial and marine) in the sediments indicate that algal and aquatic macrophyte derived OM inputs dominated over terrigenous plant sources. The lignin-derived methoxyphenol assemblage, dominated by vinylguaiacol and vinylsyringol derivatives in all sediments, points to large OM contribution from higher plants. The spatial distributions of PAHs (polyaromatic hydrocarbons) showed that most pollution sources were mixed sources including both pyrogenic and petrogenic. Low carbon preference indexes (CPI > 1) for n-alkanes, the presence of UCM (unresolved complex mixture) and the distribution of hopanes (C-29-C-36) and steranes (C-27-C-29) suggested localized petroleum-derived hydrocarbon inputs to the core sediments. Series of LABs were found in most sediment samples also pointing to domestic sewage anthropogenic contributions to the sediment OM.EU Erasmus Mundus Joint Doctorate fellowship (FUECA, University of Cadiz, Spain)EUEuropean Commission [FP7-ENV-2011, 282845, FP7-534 ENV-2012, 308392]MINECO project INTERCARBON [CGL2016-78937-R]info:eu-repo/semantics/publishedVersio