Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

Purpose 111In (typically as [111In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an 89Zr PET tracer for cell labelling and compare it with [111In]oxinate3 single photon emission computed tomography (SPECT). Methods [89Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3 was monitored for up to 14 days. 89Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. Results Zr labelling was effective in all cell types with yields comparable with 111In labelling. Retention of 89Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with 111In or 89Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for 111In. In liver, spleen and bone marrow at least 92 % of 89Zr remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [89Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

Latent Print Proficiency Testing: An Examination of Test Respondents, Test‐Taking Procedures, and Test Characteristics

Proficiency testing is a key component of quality assurance programs within crime laboratories and can help improve laboratory practices. However, current proficiency testing procedures contain significant limitations and can be misinterpreted by examiners and court personnel (Garrett & Mitchell, 2018). To evaluate some of these limitations, we surveyed latent print examiners (n = 198) after they completed a Collaborative Testing Services, Inc. proficiency test. Additionally, we evaluated test performance and used a quality metric algorithm to evaluate the quality of test prints. Results do not suggest that respondents are dissimilar to the broader examiner population, although they may engage in different behaviors when completing tests versus casework. Findings show that proficiency testing contains prints of high quality and is perceived as both relatively easy and representative of casework. The test discriminated between inexperienced and experienced respondents, and verification procedures were largely ineffective in reducing errors. Objective quality metrics may provide a path forward to improving proficiency testing in a measurable manner

Superconformal index, BPS monodromy and chiral algebras

We show that specializations of the 4d N = 2 superconformal index labeled by an integer N is given by Tr M-N where M is the Kontsevich-Soibelman monodromy operator for BPS states on the Coulomb branch. We provide evidence that the states enumerated by these limits of the index lead to a family of 2d chiral algebras A(N). This generalizes the recent results for the N = -1 case which corresponds to the Schur limit of the superconformal index. We show that this specialization of the index leads to the same integrand as that of the elliptic genus of compactification of the superconformal theory on S-2 x T-2 where we turn on 1/2 N units of U(1)(r) flux on S-2

Future climate effects on suitability for growth of oil palms in Malaysia and Indonesia

The production of palm oil (PO) is highly profitable. The economies of the principal producers, Malaysia and Indonesia, and others, benefit considerably. Climate change (CC) will most likely have an impact on the distribution of oil palms (OP) (Elaeis guineensis). Here we present modelled CC projections with respect to the suitability of growing OP, in Malaysia and Indonesia. A process-oriented niche model of OP was developed using CLIMEX to estimate its potential distribution under current and future climate scenarios. Two Global Climate Models (GCMs), CSIRO-Mk3.0 and MIROC-H, were used to explore the impacts of CC under the A1B and A2 scenarios for 2030, 2070 and 2100. Decreases in climatic suitability for OP in the region were gradual by 2030 but became more pronounced by 2100. These projections imply that OP growth will be affected severely by CC, with obvious implications to the economies of (a) Indonesia and Malaysia and (b) the PO industry, but with potential benefits towards reducing CC. A possible remedial action is to concentrate research on development of new varieties of OP that are less vulnerable to CC.The Portuguese-based authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioEnv - Biotechnology and Bioengineering for a sustainable world", REF. NORTE-07-0124-FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 µM DXR P<0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P<0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer

Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence

<p>Abstract</p> <p>Background</p> <p>Entomopathogenic fungi <it>Metarhizium anisopliae </it>and <it>Beauveria bassiana </it>isolates have been shown to infect and reduce the survival of mosquito vectors.</p> <p>Methods</p> <p>Here four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates <it>M. anisopliae </it>ICIPE-30 and <it>B. bassiana </it>I93-925 on infection and survival rates of female <it>Anopheles gambiae sensu stricto</it>. Test concentrations and exposure times ranged between 1 × 10⁷- 4 × 10¹⁰conidia m^-2and 15 min - 6 h. In co-formulations, 2 × 10¹⁰conidia m^-2of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 × 10⁹, 2 × 10¹⁰or 4 × 10¹⁰.</p> <p>Results</p> <p>Mosquito survival varied with conidia concentration; 2 × 10¹⁰conidia m^-2was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d). Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence.</p> <p>Conclusion</p> <p>Both fungus isolates are effective and persistent at low concentrations and short exposure times.</p