Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes

Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive

Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area?

To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had ⩾ 10 000 P. falciparum parasites per μL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia ⩾ 10 000/μL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature ⩾ 38 °C had the best predictive value for a P. falciparum parasitaemia ⩾ 10 000 μL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia ⩾ 10 000/μL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considere

Relationships between Plasmodium falciparum infection and morbidity in a highly endemic area

A total of 736 outpatients diagnosed as having malaria using clinical criteria at a health centre in a highly endemic area of Papua New Guinea were investigated parasitologically. Plasmodium falciparum-attributable fractions were determined using a logistic regression model to compare parasite densities in cases with those of healthy individuals in community surveys. Thirty-seven percent of presumptive cases were found to have raised P. falciparum parasitaemia. This corresponds to an average reporting rate for the population of 0·53 attributable episodes per annum. Whilst the maximum prevalence of parasitaemia in the community was in children aged 5-9 years, the maximum age-specific incidence of attributable cases at the outpatient clinic was 2 cases per annum in the 2- to 4-year-old age group. The procedure for estimating attributable fractions makes it possible to compare morbidity rates between age groups, and to examine how the relationship between morbidity risk and parasite density changes with age, without diagnosing individual episodes. The average tolerance of parasites in an age group was measured by considering the level of parasitaemia associated with a given risk of malaria-attributable morbidity. In contrast to anti-parasite immunity, tolerance of parasites declines with age since at parasite isodensity the probability of being symptomatic increases with ag

Efficient Surveillance of Plasmodium knowlesi Genetic Subpopulations, Malaysian Borneo, 2000-2018.

Population genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially

From haemoglobin to single-site hydrogenation catalyst

Iron-based single-site catalysts hold immense potential for achieving highly selective chemical processes, with the added advantage of iron being an earth-abundant metal. They are widely explored in electrocatalysis for oxygen reduction and display promising catalytic activity for organic transformations. In particular, FeNx@C catalysts are active for the reduction of nitroarene into aromatic amines. Yet, they are difficult to mass-produce, and most preparation methods fail to avoid single site aggregation. Here we prepared FeNx@C catalysts from bio-derived compounds, xylose and haemoglobin, in a simple two-step process. Since haemoglobin naturally contains FeNx single-sites, we successfully repurposed them into hydrogenation catalytic centers and avoided their aggregation during the preparation of the material. Their single-site nature was demonstrated by aberration-corrected transmission electron microscopy and X-ray absorption techniques. They were shown to be active for transfer hydrogenation of nitroarenes into anilines, with excellent substrate selectivity and recyclability, as demonstrated by the preserved yield across seven catalytic cycles. We also showed that FeNx@C could be used to prepare 2-phenylbenzimidazole through a reduction/condensation tandem. Our work shows for the first time the viability of biomass precursors to prepare Fe single-site hydrogenation catalysts

Structure and bonding of [(SIPr)AgX] (X = Cl, Br, i and OTf)

© 2015 The Royal Society of Chemistry.A series of iso-structural complexes [(SIPr)AgX] (X = Cl, Br, I, OTf; SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolidene) were synthesised, including the first example of a N-heterocyclic carbene silver(i) complex containing an O-bound triflate. Bond Energy Dissociation and Natural Orbitals for Chemical Valence bond analyses (BEDA & ETS-NOCV) revealing a significant NHC → M σ-back-donation, which influences the stability and sigma-donicity of these complexes.Link_to_subscribed_fulltex

Operational efficiency and sustainability of vector control of malaria and dengue: descriptive case studies from the Philippines

Background: Analysis is lacking on the management of vector control systems in disease-endemic countries with respect to the efficiency and sustainability of operations. Methods: Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions. Results: Adaptation of disease control strategies to the epidemiological situation per barangay, through microstratification, brings gains in efficiency, but should be accompanied by further capacity building on local situational analysis for better selection and targeting of vector control interventions within the barangay. An integrated approach to vector control, aiming to improve the rational use of resources, was evident with a multi-disease strategy for detection and response, and by the use of combinations of vector control methods. Collaboration within the health sector was apparent from the involvement of barangay health workers, re-orientation of job descriptions and the creation of a disease surveillance unit. The engagement of barangay leaders and use of existing community structures helped mobilize local resources and voluntary services for vector control. In one location, local authorities and the community were involved in the planning, implementation and evaluation of malaria control, which triggered local programme ownership. Conclusions: Strategies that contributed to an improved efficiency and sustainability of vector control operations were: micro-stratification, integration of vector control within the health sector, a multi-disease approach, involvement of local authorities, and empowerment of communities. Capacity building on situational analysis and vector surveillance should be addressed through national policy and guidelines

Quantifying Dispersal of European Culicoides (Diptera: Ceratopogonidae) Vectors between Farms Using a Novel Mark-Release-Recapture Technique

Studying the dispersal of small flying insects such as Culicoides constitutes a great challenge due to huge population sizes and lack of a method to efficiently mark and objectively detect many specimens at a time. We here describe a novel mark-release-recapture method for Culicoides in the field using fluorescein isothiocyanate (FITC) as marking agent without anaesthesia. Using a plate scanner, this detection technique can be used to analyse thousands of individual Culicoides specimens per day at a reasonable cost. We marked and released an estimated 853 specimens of the Pulicaris group and 607 specimens of the Obsoletus group on a cattle farm in Denmark. An estimated 9,090 (8,918-9,260) Obsoletus group specimens and 14,272 (14,194-14,448) Pulicaris group specimens were captured in the surroundings and subsequently analysed. Two (0.3%) Obsoletus group specimens and 28 (4.6%) Pulicaris group specimens were recaptured. The two recaptured Obsoletus group specimens were caught at the release point on the night following release. Eight (29%) of the recaptured Pulicaris group specimens were caught at a pig farm 1,750 m upwind from the release point. Five of these were recaptured on the night following release and the three other were recaptured on the second night after release. This is the first time that movement of Culicoides vectors between farms in Europe has been directly quantified. The findings suggest an extensive and rapid exchange of disease vectors between farms. Rapid movement of vectors between neighboring farms may explain the the high rate of spatial spread of Schmallenberg and bluetongue virus (BTV) in northern Europe