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Classical mosquito control methods (e.g. chemical fogging) struggle to sustain long-term reductions in mosquito populations to combat vector-borne diseases like dengue. The Mosquito Home System (MHS) is an auto-dissemination mosquito trap, that kills mosquito larvae before they hatch into adult mosquitoes. A novel hybrid stochastic-deterministic model is presented, that successfully predicts the effect of deploying MHSs within high-rise flats in Selangor, Malaysia. Stochastic SIR (Susceptible-Infected-Recovered) equations (flats) are paired with an existing deterministic SIR model (wider Kuala Lumpur population). Model predictions provide excellent agreement with data from a 44 week MHS trial within the flats. The stochastic model is validated as a powerful tool for predicting short- and long-term impacts of deploying this style of trap within similar environments. Significant, sustainable reductions in mosquito populations are predicted when the MHS is active: with a mean of 9 (95% Uncertainty Range (UR): 1; 30) during the 44 week trial period, compared to 35 (95% UR: 1; 234) dengue cases with no MHSs. Long-term predictions for endemic equilibrium show MHSs significantly narrow the mosquito population distribution and reduce dengue prevalence: from a mean of 5 (95% UR: 0; 52) (no MHS), to 1 (95% UR: 0; 8) dengue cases annually (with MHS).

Several sites, Z-7L, Z-5 and Z-14, in Sibu district, Sarawak, Malaysia, experienced intense dengue transmission in 2014 that continued into 2015. A pilot study with Bacillus thuringiensis israelensis (Bti) to control Aedes aegypti (L.) and Ae. albopictus (Skuse) was evaluated in Z-7L, a densely populated site of 12 ha. Bti treatments were conducted weekly from epidemiology week (EW) 24/2015 for 4 weeks, followed by fortnight treatments for 2 months, in addition to the routine control activities. Bti was directly introduced into potable containers and the outdoor artificial and natural containers were treated via a wide area spray application method using a backpack mister. Aedes indices significantly reduced during the treatment and post treatment phases, compared to the control site, Z-5 (p

p16[SUPINK4A] (p16) tumour suppressor induces growth arrest by inhibiting function of cyclin-dependent kinase (CDK)4 and CDK6. Homozygous p16 gene deletion is frequent in primary rhabdomyosarcoma (RMS) cells as well as derived cell lines. To confirm the significance ofp16 gene deletion in tumour biology of RMS, a temperature-sensitivep16 mutant (E119G) gene was retrovirally transfected into the human RMS cell line RD, which has homozygous gene deletion ofp16 gene. Decrease from 40°C (restrictive) to 34°C (permissive) culture temperature reduced CDK6-associated kinase activity and induced G1 growth arrest. Moreover, RD-p16 cells cultured under permissive condition demonstrated differentiated morphology coupled with expressions of myogenin and myosin light chain. These suggest that deletion ofp16 gene may not only facilitate growth but also inhibit the myogenic differentiation of RD RMS cells. [ABSTRACT FROM AUTHOR]

Dengue is the most important mosquito-borne viral disease. No specific treatment or vaccine is currently available; traditional vector control methods can rarely achieve adequate control. Recently, the RIDL (Release of Insect carrying Dominant Lethality) approach has been developed, based on the sterile insect technique, in which genetically engineered 'sterile' homozygous RIDL male insects are released to mate wild females; the offspring inherit a copy of the RIDL construct and die. A RIDL strain of the dengue mosquito, Aedes aegypti, OX513A, expresses a fluorescent marker gene for identification (DsRed2) and a protein (tTAV) that causes the offspring to die. We examined whether these proteins could adversely affect predators that may feed on the insect. Aedes aegypti is a peri-domestic mosquito that typically breeds in small, rain-water-filled containers and has no specific predators. Toxorhynchites larvae feed on small aquatic organisms and are easily reared in the laboratory where they can be fed exclusively on mosquito larvae. To evaluate the effect of a predator feeding on a diet of RIDL insects, OX513A Ae. aegypti larvae were fed to two different species of Toxorhynchites (Tx. splendens and Tx. amboinensis) and effects on life table parameters of all life stages were compared to being fed on wild type larvae. No significant negative effect was observed on any life table parameter studied; this outcome and the benign nature of the expressed proteins (tTAV and DsRed2) indicate that Ae. aegypti OX513A RIDL strain is unlikely to have any adverse effects on predators in the environment.

BackgroundDengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods. However, this requires that lab-reared, modified mosquitoes be able to survive and disperse adequately in the field.Methodology/principal findingsAdult male mosquitoes were released into an uninhabited forested area of Pahang, Malaysia. Their survival and dispersal was assessed by use of a network of traps. Two strains were used, an engineered 'genetically sterile' (OX513A) and a wild-type laboratory strain, to give both absolute and relative data about the performance of the modified mosquitoes. The two strains had similar maximum dispersal distances (220 m), but mean distance travelled of the OX513A strain was lower (52 vs. 100 m). Life expectancy was similar (2.0 vs. 2.2 days). Recapture rates were high for both strains, possibly because of the uninhabited nature of the site.Conclusions/significanceAfter extensive contained studies and regulatory scrutiny, a field release of engineered mosquitoes was safely and successfully conducted in Malaysia. The engineered strain showed similar field longevity to an unmodified counterpart, though in this setting dispersal was reduced relative to the unmodified strain. These data are encouraging for the future testing and implementation of genetic control strategies and will help guide future field use of this and other engineered strains.

Abstract Background Truncated variants of Ku86 protein have previously been detected in 86% to 100% of freshly isolated patient multiple myeloma (MM) cells. Since, the Ku70/Ku86 heterodimer functions as the regulatory subunit of the DNA repair enzyme, DNA-dependent protein kinase, we have been interested in the altered expression and function of Ku86 variant (Ku86v) proteins in genome maintenance of MM. Results Although, a number of studies have suggested that truncated forms of Ku proteins could be artificially generated by proteolytic degradation in vitro in human lymphocytes, we now show using whole cell immunoblotting that the RPMI-8226 and SGH-MM5 human MM cell lines consistently express full-length Ku86 as well as a 69-kDa Ku86v; a C-terminus truncated 69-kDa variant Ku86 protein. In contrast, Ku86v proteins were not detected in the freshly isolated lymphocytes as was previously reported. Data also indicates that the Ku86v was not generated as a result of carbohydrate modification but that serine proteases may act on the full-length form of the protein. Conclusion These data confirm that MM cells contain bona fide Ku86v proteins that were generated intracellularly by a post-transcriptional mechanism, which required proteolytic processing.