Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells

Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminogen-dependent fibrinolytic activity in 125I fibrin assays; this activity was associated with urokinase plasminogen activator, as shown by casein zymography and Western blotting. Urokinase was bound to its high affinity receptor on the vesicle membrane. Addition of plasminogen resulted in activation of the progelatinases associated with the vesicles, indicating a role of the urokinase-plasmin system in MMP-2 and MMP-9 activation. We propose that vesicles shed by tumor cells may provide a large membrane surface for the activation of membrane-associated proteinases involved in extracellular matrix degradation and tissue invasion

Comparative study of T84 and T84SF human colon carcinoma cells: in vitro and in vivo ultrastructural and functional characterization of cell culture and metastasis

To better understand the relationship between tumor heterogeneity, differentiation, and metastasis, suitable experimental models permitting in vitro and in vivo studies are necessary. A new variant cell line (T84SF) exhibiting an altered phenotype was recently selected from a colon cancer cell line (T84) by repetitive plating on TNF-alpha treated human endothelial cells and subsequent selection for adherent cells. The matched pair of cell lines provides a useful system to investigate the extravasation step of the metastatic cascade. Since analysis of morphological differences can be instructive to the understanding of metastatic potential of tumor cells, we compared the ultrastructural and functional phenotype of T84 and T84SF cells in vitro and in vivo. The reported ultrastructural features evidence differences between the two cell lines; selected cells showed a marked pleomorphism of cell size and nuclei, shape, and greater surface complexity. These morphological differences were also coupled with biochemical data showing a distinct tyrosine phosphorylation-based signaling, an altered localization of beta-catenin, MAPK, and AKT activation, as well as an increased expression in T84SF cells of Bcl-X-L, a major regulator of apoptosis. Therefore, these cell lines represent a step forward in the development of appropriate models in vitro and in vivo to investigate colon cancer progression

Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé foci, Mali

In Mali, ivermectin-based onchocerciasis elimination from the Bakoye and Falémé foci, reported in 2009–2012, was a beacon leading to policy shifting from morbidity control to elimination of transmission (EOT). These foci are also endemic for lymphatic filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to evaluate if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved

Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. METHODS: A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. RESULTS: It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (<1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. CONCLUSIONS: The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency

Anopheles larval abundance and diversity in three rice agro-village complexes Mwea irrigation scheme, central Kenya

<p>Abstract</p> <p>Background</p> <p>The diversity and abundance of <it>Anopheles </it>larvae has significant influence on the resulting adult mosquito population and hence the dynamics of malaria transmission. Studies were conducted to examine larval habitat dynamics and ecological factors affecting survivorship of aquatic stages of malaria vectors in three agro-ecological settings in Mwea, Kenya.</p> <p>Methods</p> <p>Three villages were selected based on rice husbandry and water management practices. Aquatic habitats in the 3 villages representing planned rice cultivation (Mbui Njeru), unplanned rice cultivation (Kiamachiri) and non-irrigated (Murinduko) agro-ecosystems were sampled every 2 weeks to generate stage-specific estimates of mosquito larval densities, relative abundance and diversity. Records of distance to the nearest homestead, vegetation coverage, surface debris, turbidity, habitat stability, habitat type, rice growth stage, number of rice tillers and percent <it>Azolla </it>cover were taken for each habitat.</p> <p>Results</p> <p>Captures of early, late instars and pupae accounted for 78.2%, 10.9% and 10.8% of the total <it>Anopheles </it>immatures sampled (n = 29,252), respectively. There were significant differences in larval abundance between 3 agro-ecosystems. The village with 'planned' rice cultivation had relatively lower <it>Anopheles </it>larval densities compared to the villages where 'unplanned' or non-irrigated. Similarly, species composition and richness was higher in the two villages with either 'unplanned' or limited rice cultivation, an indication of the importance of land use patterns on diversity of larval habitat types. Rice fields and associated canals were the most productive habitat types while water pools and puddles were important for short periods during the rainy season. Multiple logistic regression analysis showed that presence of other invertebrates, percentage <it>Azolla </it>cover, distance to nearest homestead, depth and water turbidity were the best predictors for <it>Anopheles </it>mosquito larval abundance.</p> <p>Conclusion</p> <p>These results suggest that agricultural practices have significant influence on mosquito species diversity and abundance and that certain habitat characteristics favor production of malaria vectors. These factors should be considered when implementing larval control strategies which should be targeted based on habitat productivity and water management.</p

Trends in malaria morbidity among health care-seeking children under age five in Mopti and Sévaré, Mali between 1998 and 2006

<p>Abstract</p> <p>Background</p> <p>In Mali, malaria is the leading cause of death and the primary cause of outpatient visits for children under five. The twin towns of Mopti and Sévaré have historically had high under-five mortality. This paper investigates the changing malaria burden in children under five in these two towns for the years 1998-2006, and the likely contribution of previous interventions aimed at reducing malaria.</p> <p>Methods</p> <p>A retrospective analysis of daily outpatient consultation records from urban community health centres (CSCOMs) located in Mopti and Sévaré for the years 1998-2006 was conducted. Risk factors for a diagnosis of presumptive malaria, using logistic regression and trends in presumptive malaria diagnostic rates, were assessed using multilevel analysis.</p> <p>Results</p> <p>Between 1998-2006, presumptive malaria accounted for 33.8% of all recorded consultation diagnoses (10,123 out of 29,915). The monthly presumptive malaria diagnostic rate for children under five decreased by 66% (average of 8 diagnoses per month per 1,000 children in 1998 to 2.7 diagnoses per month in 2006). The multi-level analysis related 37% of this decrease to the distribution of bed net treatment kits initiated in May of 2001. Children of the Fulani (Peuhl) ethnicity had significantly lower odds of a presumptive malaria diagnosis when compared to children of other ethnic groups.</p> <p>Conclusions</p> <p>Presumptive malaria diagnostic rates have decreased between 1998-2006 among health care-seeking children under five in Mopti and Sévaré. A bed net treatment kit intervention conducted in 2001 is likely to have contributed to this decline. The results corroborate previous findings that suggest that the Fulani ethnicity is protective against malaria. The findings are useful to encourage dialogue around the urban malaria situation in Mali, particularly in the context of achieving the target of reducing malaria morbidity in children younger than five by 50% by 2011 as compared to levels in 2000.</p

L’insediamento a bifacciali di Guado San Nicola (Monteroduni, Molise, Italia)

La monografia rappresenta un compendio di lavori specialistici sul sito paleolitico di Guado San Nicola a Monteroduni (Molise, Italia), oggetto di ricerche sistematiche ed indagini interdisciplinari inaugurate nell’area a partire dal 2000 dall'Università degli Studi di Ferrara. Il sito, ascrivibile al MIS 10/11, costituisce un tassello importante nell’ambito della ricostruzione del quadro del popolamento umano della penisola italiana e dell’intero bacino del Mediterraneo, alla luce delle considerazioni crono-stratigrafiche, della ricchezza della documentazione e della presenza di elementi innovativi dal punto di vista culturale quali la padronanza del metodo Levallois e l’uso di percussori in palchi di cervo

Malaria vector control practices in an irrigated rice agro-ecosystem in central Kenya and implications for malaria control

<p>Abstract</p> <p>Background</p> <p>Malaria transmission in most agricultural ecosystems is complex and hence the need for developing a holistic malaria control strategy with adequate consideration of socio-economic factors driving transmission at community level. A cross-sectional household survey was conducted in an irrigated ecosystem with the aim of investigating vector control practices applied and factors affecting their application both at household and community level.</p> <p>Methods</p> <p>Four villages representing the socio-economic, demographic and geographical diversity within the study area were purposefully selected. A total of 400 households were randomly sampled from the four study villages. Both semi-structured questionnaires and focus group discussions were used to gather both qualitative and quantitative data.</p> <p>Results</p> <p>The results showed that malaria was perceived to be a major public health problem in the area and the role of the vector <it>Anopheles </it>mosquitoes in malaria transmission was generally recognized. More than 80% of respondents were aware of the major breeding sites of the vector. Reported personal protection methods applied to prevent mosquito bites included; use of treated bed nets (57%), untreated bed nets (35%), insecticide coils (21%), traditional methods such as burning of cow dung (8%), insecticide sprays (6%), and use of skin repellents (2%). However, 39% of respondents could not apply some of the known vector control methods due to unaffordability (50.5%), side effects (19.9%), perceived lack of effectiveness (16%), and lack of time to apply (2.6%). Lack of time was the main reason (56.3%) reported for non-application of environmental management practices, such as draining of stagnant water (77%) and clearing of vegetations along water canals (67%).</p> <p>Conclusion</p> <p>The study provides relevant information necessary for the management, prevention and control of malaria in irrigated agro-ecosystems, where vectors of malaria are abundant and disease transmission is stable.</p