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PubMed | University Malaysia Sarawak, University of Washington, Eijkman Oxford Clinical Research Unit, Chulalongkorn University and 4 more.
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2016

Infection by the simian malaria parasite, Plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of Malaysia. Despite being a serious public health concern, the geographical distribution of P. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. Human cases have been confirmed in at least nine Southeast Asian countries, many of which are making progress towards eliminating the human malarias. Understanding the geographical distribution of P. knowlesi is important for identifying areas where malaria transmission will continue after the human malarias have been eliminated.A total of 439 records of P. knowlesi infections in humans, macaque reservoir and vector species were collated. To predict spatial variation in disease risk, a model was fitted using records from countries where the infection data coverage is high. Predictions were then made throughout Southeast Asia, including regions where infection data are sparse. The resulting map predicts areas of high risk for P. knowlesi infection in a number of countries that are forecast to be malaria-free by 2025 (Malaysia, Cambodia, Thailand and Vietnam) as well as countries projected to be eliminating malaria (Myanmar, Laos, Indonesia and the Philippines).We have produced the first map of P. knowlesi malaria risk, at a fine-scale resolution, to identify priority areas for surveillance based on regions with sparse data and high estimated risk. Our map provides an initial evidence base to better understand the spatial distribution of this disease and its potential wider contribution to malaria incidence. Considering malaria elimination goals, areas for prioritised surveillance are identified.


Bruneau P.,CNRS Nantes Atlantic Computer Science Laboratory | Bruneau P.,Atlas Project | Picarougne F.,CNRS Nantes Atlantic Computer Science Laboratory | Gelgon M.,CNRS Nantes Atlantic Computer Science Laboratory | Gelgon M.,Atlas Project
Pattern Recognition | Year: 2010

In this paper, we propose an approach to interactive navigation in image collections. As structured groups are more appealing to users than flat image collections, we propose an image clustering algorithm, with an incremental version that handles time-varying collections. A 3D graph-based visualization technique reflects the classification state. While this classification visualization is itself interactive, we show how user feedback may assist the classification, thus enabling a user to improve it. © 2009 Elsevier Ltd. All rights reserved.


Bruneau P.,CNRS Nantes Atlantic Computer Science Laboratory | Bruneau P.,Atlas Project | Gelgon M.,CNRS Nantes Atlantic Computer Science Laboratory | Gelgon M.,Atlas Project | Picarougne F.,CNRS Nantes Atlantic Computer Science Laboratory
Pattern Recognition | Year: 2010

Aggregating statistical representations of classes is an important task for current trends in scaling up learning and recognition, or for addressing them in distributed infrastructures. In this perspective, we address the problem of merging probabilistic Gaussian mixture models in an efficient way, through the search for a suitable combination of components from mixtures to be merged. We propose a new Bayesian modelling of this combination problem, in association to a variational estimation technique, that handles efficiently the model complexity issue. A main feature of the present scheme is that it merely resorts to the parameters of the original mixture, ensuring low computational cost and possibly communication, should we operate on a distributed system. Experimental results are reported on real data. © 2009 Elsevier Ltd. All rights reserved.


Sooman L.,Rudbeck Laboratory | Freyhult E.,Uppsala University | Jaiswal A.,Atlas Project | Navani S.,Atlas Project | And 10 more authors.
Acta Oncologica | Year: 2015

Background. The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients. Methods. Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes. Results. The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found. Conclusion. FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation. © 2014 Informa Healthcare.


News Article | December 12, 2016
Site: www.eurekalert.org

Arginine-degrading-enzyme therapy is beneficial for the treatment of cancers lacking the enzyme needed for arginine synthesis (argininosuccinate synthetase 1), according to a new report in The American Journal of Pathology Philadelphia, PA, December 12, 2016 - With few treatment options available to patients with advanced bladder cancer, investigators are looking for novel molecular targets. In a study published in The American Journal of Pathology, researchers report that more than 90% of all bladder cancers are deficient in argininosuccinate synthetase 1 (ASS1), an enzyme necessary for arginine synthesis, and patients with tumors having low ASS1 expression have shorter survival. Treatment with the arginine-degrading enzyme ADI-PEG 20 inhibited tumor growth in ASS1-deficient cells both in vivo and in vitro, suggesting a new therapeutic approach to bladder cancer is possible. "There is a major unmet need to identify additional therapies for bladder cancer patients that includes agents that can target both conventional urothelial carcinoma and less common subtypes of bladder cancer. Our findings suggest that arginine dependency in bladder cancer may be a useful mechanism to selectively target a subset of these cancers using ADI-PEG 20, although further investigation into the mediators of this effect and the role of combination therapy, including chemotherapy, to enhance efficacy is required," explained lead investigator Donna Hansel, MD, PhD, Professor of Pathology, University of California at San Diego (CA). Using immunohistochemistry on tissue specimens taken from 252 patients who had undergone surgery for muscle-invasive bladder cancer over a 20-year period, investigators found that normal urothelium demonstrated robust ASS1 expression throughout its full thickness. Although the majority of samples with urothelial carcinoma, small cell carcinoma, and squamous cell carcinoma showed significant reductions in ASS1 expression, moderate-to-intense ASS1 expression was retained in the great majority of those with invasive bladder adenocarcinomas and invasive micropapillary urothelial carcinomas. "This finding suggests that these three major subtypes of bladder cancer, which account for more than 90% of all bladder cancers, may potentially respond to arginine-degrading therapy such as ADI-PEG 20," noted Dr. Hansel. Using data from The Cancer Genome Atlas Project, the investigators examined survival data after classifying cases according to ASS1 mRNA expression levels. They found that survival was significantly lower in patients having tumors with low ASS1 expression compared to those with high ASS1 expression. To evaluate the effects of ADI-PEG 20, the researchers compared its effects on cells that were deficient in ASS1 to those that express ASS1. They found that ADI-PEG 20 decreased colony formation and reduced cell viability only in cells deficient in ASS1 but had little or no effect on other cells. To test the effects of ADI-PEG 20 in vivo, mice were injected with ASS1-deficient cells into subcutaneous tissue in the left flank and ASS1-expressor cells into the right flank. The result was that ADI-PEG 20 arrested tumor growth only in tissue containing ASS1-deficient cells. In addition to bladder cancer, ADI-PEG 20 is currently being evaluated in a Phase III trial for hepatocellular carcinoma and is being assessed for other cancers including melanoma and mesothelioma. "Our results suggest that arginine deprivation may be a useful strategy for treating bladder cancer and show that ADI-PEG 20 functions through a novel signaling mechanism that includes the pathway mediated by the general control nonderepressible 2 kinase that controls autophagy and apoptosis," commented Dr. Hansel. Arginine is a semi-essential amino acid that is synthesized from citrulline in two steps of the urea cycle. In the first step, citrulline and aspartate are converted to argininosuccinate via the enzyme ASS1. The argininosuccinate is then converted to arginine and fumarate. Arginase and arginine deiminase (ADI) are arginine-degrading enzymes. ADI-PEG 20 is a commercial formulation of ADI that has a longer pharmacokinetic half-life.


Eriksson O.,Uppsala University | Thulin,Uppsala University | Asplund A.,Uppsala University | Hegde G.,Atlas Project | And 2 more authors.
BMC Cancer | Year: 2016

Background: Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens. Methods: Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry. Results: TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated. Conclusions: These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo. © 2016 The Author(s).


Pio D.V.,University of Lausanne | Pio D.V.,Swiss Institute of Bioinformatics | Broennimann O.,University of Lausanne | Barraclough T.G.,Imperial College London | And 7 more authors.
Conservation Biology | Year: 2011

Considering genetic relatedness among species has long been argued as an important step toward measuring biological diversity more accurately, rather than relying solely on species richness. Some researchers have correlated measures of phylogenetic diversity and species richness across a series of sites and suggest that values of phylogenetic diversity do not differ enough from those of species richness to justify their inclusion in conservation planning. We compared predictions of species richness and 10 measures of phylogenetic diversity by creating distribution models for 168 individual species of a species-rich plant family, the Cape Proteaceae. When we used average amounts of land set aside for conservation to compare areas selected on the basis of species richness with areas selected on the basis of phylogenetic diversity, correlations between species richness and different measures of phylogenetic diversity varied considerably. Correlations between species richness and measures that were based on the length of phylogenetic tree branches and tree shape were weaker than those that were based on tree shape alone. Elevation explained up to 31% of the segregation of species rich versus phylogenetically rich areas. Given these results, the increased availability of molecular data, and the known ecological effect of phylogenetically rich communities, consideration of phylogenetic diversity in conservation decision making may be feasible and informative. ©2011 Society for Conservation Biology.


Durham J.,University of Queensland | Battle K.,Atlas Project | Rickart K.,Communicable Disease Unit | Shanks G.D.,Australian Army Malaria Institute
Disaster Medicine and Public Health Preparedness | Year: 2014

Objective In Cambodia, a highly landmine-contaminated country with endemic malaria, symptomatic falciparum malaria has been observed in patients presenting with traumatic landmine injuries. Because a link between recrudescence of symptomatic Plasmodium falciparum malaria and severe trauma is well established, we explored whether a link could be demonstrated between the geolocation of landmine amputations and malaria cases.Method: Landmine amputation data in Cambodia (2005-2008) were compared with predicted measures of malaria endemicity. Data of injuries that had resulted in amputation were plotted over a surface of P falciparum parasite rates.Results: No statistically significant correlation was found, possibly because the P falciparum endemicity surface was drawn from a model-based geostatistical prediction of infection prevalence and did not distinguish cases of recrudescence. The implication of this finding is that where symptomatic falciparum malaria has been observed in patients with landmine injuries, the cases were likely to be reactivated falciparum infections and not new cases.Conclusions: Further research is needed to understand the relationship between P falciparum and trauma. To distinguish P falciparum recrudescence from new cases, a prospective registry is needed. Also, practitioners need to be aware of the possibility of post-injury malaria recrudescence in complex emergencies. Copyright © 2014 Society for Disaster Medicine and Public Health, Inc.


PubMed | Uppsala University and Atlas Project
Type: | Journal: BMC cancer | Year: 2016

Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens.Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry.TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated.These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.


PubMed | 3Australian Army Malaria Institute, Communicable Disease Unit, University of Queensland and Atlas Project
Type: Journal Article | Journal: Disaster medicine and public health preparedness | Year: 2014

In Cambodia, a highly landmine-contaminated country with endemic malaria, symptomatic falciparum malaria has been observed in patients presenting with traumatic landmine injuries. Because a link between recrudescence of symptomatic Plasmodium falciparum malaria and severe trauma is well established, we explored whether a link could be demonstrated between the geolocation of landmine amputations and malaria cases.Landmine amputation data in Cambodia (2005-2008) were compared with predicted measures of malaria endemicity. Data of injuries that had resulted in amputation were plotted over a surface of P falciparum parasite rates.No statistically significant correlation was found, possibly because the P falciparum endemicity surface was drawn from a model-based geostatistical prediction of infection prevalence and did not distinguish cases of recrudescence. The implication of this finding is that where symptomatic falciparum malaria has been observed in patients with landmine injuries, the cases were likely to be reactivated falciparum infections and not new cases.Further research is needed to understand the relationship between P falciparum and trauma. To distinguish P falciparum recrudescence from new cases, a prospective registry is needed. Also, practitioners need to be aware of the possibility of post-injury malaria recrudescence in complex emergencies.

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