An examination of the molecular mechanisms controlling the tissue accumulation of conjugated linoleic acid (CLA) in cattle

End of project reportLong chain n-3 polyunsaturated fatty acids (n-3 PUFA) and conjugated linoleic acid (CLA) have demonstrable and potential human health benefits in terms of preventing cancer, diabetes, chronic inflammation, obesity and coronary heart disease. Supplementation of cattle diets with a blend of oils rich in n-3 PUFA and linoleic acid have a synergistic effect on the accumulation of ruminal and tissue concentrations of trans vaccenic acid (TVA), the main substrate for ?-9 desaturase which is responsible for de novo tissue synthesis of the cis 9, trans 11 isomer of CLA. This dietary strategy translates into increases in milk concentrations of CLA in dairy cows; however, concentrations in the muscle of beef animals have not always been increased. There is an apparent paradox in that n-3 PUFA supplementation enhances ruminal synthesis of trans-vaccenic acid (TVA), but then inhibits its conversion to CLA possibly through altering the activity of ?-9 desaturase. Recently, the promoter regions of the bovine ?- 9 desaturase gene has been isolated and analysed and has been shown to contain a conserved PUFA response region

Achieving high coverage of larval-stage mosquito surveillance: challenges for a community-based mosquito control programme in urban Dar es Salaam, Tanzania

Background: Preventing malaria by controlling mosquitoes in their larval stages requires regular sensitive monitoring of vector populations and intervention coverage. The study assessed the effectiveness of operational, community-based larval habitat surveillance systems within the Urban Malaria Control Programme (UMCP) in urban Dar es Salaam, Tanzania. Methods: Cross-sectional surveys were carried out to assess the ability of community-owned resource persons (CORPs) to detect mosquito breeding sites and larvae in areas with and without larviciding. Potential environmental and programmatic determinants of habitat detection coverage and detection sensitivity of mosquito larvae were recorded during guided walks with 64 different CORPs to assess the accuracy of data each had collected the previous day. Results: CORPs reported the presence of 66.2% of all aquatic habitats (1,963/2,965), but only detected Anopheles larvae in 12.6% (29/230) of habitats that contained them. Detection sensitivity was particularly low for late-stage Anopheles (2.7%, 3/111), the most direct programmatic indicator of malaria vector productivity. Whether a CORP found a wet habitat or not was associated with his/her unfamiliarity with the area (Odds Ratio (OR) [95% confidence interval (CI)] = 0.16 [0.130, 0.203], P < 0.001), the habitat type (P < 0.001) or a fence around the compound (OR [95% CI] = 0.50 [0.386, 0.646], P < 0.001). The majority of mosquito larvae (Anophelines 57.8% (133/230) and Culicines 55.9% (461/825) were not reported because their habitats were not found. The only factor affecting detection of Anopheline larvae in habitats that were reported by CORPs was larviciding, which reduced sensitivity (OR [95% CI] = 0.37 [0.142, 0.965], P = 0.042). Conclusions: Accessibility of habitats in urban settings presents a major challenge because the majority of compounds are fenced for security reasons. Furthermore, CORPs under-reported larvae especially where larvicides were applied. This UMCP system for larval surveillance in cities must be urgently revised to improve access to enclosed compounds and the sensitivity with which habitats are searched for larvae

Exploring the contributions of bed nets, cattle, insecticides and excitorepellency to malaria control: a deterministic model of mosquito host-seeking behaviour and mortality

Domestic and personal protection measures against malaria exposure either divert host-seeking vectors to other hosts or kill those attempting to feed. Here, we explicitly model mosquito host-seeking processes in the context of local host availability and elucidate the impacts and mechanisms of pyrethroid-treated bed nets in Africa. It has been suggested that excitorepellent insecticides could increase exposure of unprotected humans by concentrating mosquito biting activity on this vulnerable group. This worst-case scenario is confirmed as a possibility where vector populations lack alternative hosts, but an approximate ‘break-even' scenario, with users experiencing little overall change in exposure, is more likely because of increased mosquito mortality while foraging for resources. Insecticidal nets are predicted to have epidemiologically significant impacts on transmission experienced by users and non-users at levels of coverage that can be achieved by sustainable net distribution systems, regardless of excitorepellency or the ecological setting. The results are consistent with the outcome of several randomised controlled trials, predicting enormous reductions in transmission at individual and community levels. As financial support, technology and distribution systems for insecticide-treated nets improve, massive reductions in malaria transmission could be realise

Modeling growing confluent tissues using a lattice Boltzmann method: interface stability and fluctuations

Tissue growth underpins a wide array of biological and developmental processes, and numerical modeling of growing systems has been shown to be a useful tool for understanding these processes. However, the phenomena that can be captured are often limited by the size of systems that can be modeled. Here, we address this limitation by introducing a lattice Boltzmann method (LBM) for a growing system that is able to efficiently model hydrodynamic length scales. The model incorporates a bounce-back approach to describing the growing front of a tissue, which we use to investigate the dynamics of the interface of growing model tissues. We find that the interface grows with scaling in agreement with the Kardar-Parisi-Zhang (KPZ) universality class when growth in the system is bulk driven. Interestingly, we also find the emergence of a previously unreported hydrodynamic instability when proliferation is restricted to the tissue edge. We then develop an analytical theory to show that the instability arises due to a coupling between the number of cells actively proliferating and the position of the interface

Protein-DNA computation by stochastic assembly cascade

The assembly of RecA on single-stranded DNA is measured and interpreted as a stochastic finite-state machine that is able to discriminate fine differences between sequences, a basic computational operation. RecA filaments efficiently scan DNA sequence through a cascade of random nucleation and disassembly events that is mechanistically similar to the dynamic instability of microtubules. This iterative cascade is a multistage kinetic proofreading process that amplifies minute differences, even a single base change. Our measurements suggest that this stochastic Turing-like machine can compute certain integral transforms.Comment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC129313/ http://www.pnas.org/content/99/18/11589.abstrac

Global gene expression in endometrium of high and low fertility heifers during the mid-luteal phase of the estrous cycle

peer-reviewedBackground In both beef and dairy cattle, the majority of early embryo loss occurs within the first 14 days following insemination. During this time-period, embryos are completely dependent on their maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to their survival. The objective of this study was to investigate whether differences in endometrial gene expression during the mid-luteal phase of the estrous cycle exist between crossbred beef heifers ranked as either high (HF) or low fertility (LF) (following four rounds of artificial insemination (AI)) using the Affymetrix® 23 K Bovine Gene Chip. Results Conception rates for each of the four rounds of AI were within a normal range: 70–73.3%. Microarray analysis of endometrial tissue collected on day 7 of the estrous cycle detected 419 differentially expressed genes (DEG) between HF (n = 6) and LF (n = 6) animals. The main gene pathways affected were, cellular growth and proliferation, angiogenesis, lipid metabolism, cellular and tissue morphology and development, inflammation and metabolic exchange. DEG included, FST, SLC45A2, MMP19, FADS1 and GALNT6. Conclusions This study highlights, some of the molecular mechanisms potentially controlling uterine endometrial function during the mid-luteal phase of the estrous cycle, which may contribute to uterine endometrial mediated impaired fertility in cattle. Differentially expressed genes are potential candidate genes for the identification of genetic variation influencing cow fertility, which may be incorporated into future breeding programmes.Teagasc Walsh Fellowship Programm

Measurement of overall insecticidal effects in experimental hut trials

BACKGROUND: The 'overall insecticidal effect' is a key measure used to evaluate public health pesticides for indoor use in experimental hut trials. It depends on the proportion of mosquitoes that are killed out of those that enter the treated hut, intrinsic mortality in the control hut, and the ratio of mosquitoes entering the treatment hut to those entering the control hut. This paper critically examines the way the effect is defined, and discusses how it can be used to infer effectiveness of intervention programmes. FINDINGS: The overall insecticidal effect, as defined by the World Health Organization in 2006, can be negative when deterrence from entering the treated hut is high, even if all mosquitoes that enter are killed, wrongly suggesting that the insecticide enhances mosquito survival. Also in the absence of deterrence, even if the insecticide kills all mosquitoes in the treatment hut, the insecticidal effect is less than 100%, unless intrinsic mortality is nil. A proposed alternative definition for the measurement of the overall insecticidal effect has the desirable range of 0 to 1 (100%), provided mortality among non-repelled mosquitoes in the treated hut is less than the corresponding mortality in the control hut. This definition can be built upon to formulate the coverage-dependent insecticidal effectiveness of an intervention programme. Coverage-dependent population protection against feeding can be formulated similarly. CONCLUSIONS: This paper shows that the 2006 recommended quantity for measuring the overall insecticidal effect is problematic, and proposes an alternative quantity with more desirable propertie

Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

&lt;p&gt;Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected.&lt;/p&gt; &lt;p&gt;Methods: From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxinepyrimethamine(SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed.&lt;/p&gt; &lt;p&gt;Results: Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p &lt; 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy.&lt;/p&gt; &lt;p&gt;Conclusions: In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressingtransmission are more likely to be evident where transmission is already low or effective vector control is widely implemented.&lt;/p&gt

Preventing childhood malaria in Africa by protecting adults from mosquitoes with insecticide-treated nets

Malaria prevention in Africa merits particular attention as the world strives toward a better life for the poorest. Insecticide-treated nets (ITNs) represent a practical means to prevent malaria in Africa, so scaling up coverage to at least 80% of young children and pregnant women by 2010 is integral to the Millennium Development Goals (MDG). Targeting individual protection to vulnerable groups is an accepted priority, but community-level impacts of broader population coverage are largely ignored even though they may be just as important. We therefore estimated coverage thresholds for entire populations at which individual- and community-level protection are equivalent, representing rational targets for ITN coverage beyond vulnerable groups