Surto de leishmaniose cutânea em General Vedia, Provincia de Chaco, 1996

Between March and July 1996, a focalized epidemic outbreak of cutaneous leishmaniasis in General Vedia, province of Chaco, associated to the gallery forest of the Oro river was verified. The incidence rate in the area, which was 0-2/000 cases in preceding years, reached 8/000 cases in 1996. The risk of symptomatic infection was similar between sexes, but was different when analizing the different age groups by sex, suggesting a greater relative importance of the peridomestic transmission for the females and of the transmission in the subtropical forest for the males. Specimens of Lutzomyia intermedia, a species already incriminated as a vector of Leishmaniasis in other provinces of northern Argentina, were captured and identified in the focus locality in May 1996. The possible causes of the outbreak related to the climatic variables and the vector abundance are analyzed and the results in the framework of possible preventive and control activities are discussed.Entre março e julho de 1996, foi verificado um surto epidêmico focalizado de leishmaniose cutânea na localidade de Geral Vedia, província de Chaco, associado com a floresta de galeria do rio de Oro. A taxa de incidência na área que era 0-2/000 casos em anos anteriores, alcançou 8/000 casos em 1996. O risco de infecção sintomática era semelhante entre sexos, mas era diferente quando foram analizados os grupos de idade diferentes segundo sexo, sugerindo maior importância relativa da transmissão na área peridoméstica nas mulheres e da transmissão na floresta subtropical nos homens. Espécimes de Lutzomyia intermedia, espécie já incriminada como vetor de Leishmaniose em outras províncias do norte da Argentina, foram capturadas e identificadas na localidade em maio de 1996. São analisadas as possíveis causas do surto relacionadas às variáveis climáticas e a abundância do vetor e os resultados são discutidas na estrutura de possíveis atividades de prevenção e controle

Surto de leishmaniose cutânea americana na cidade de Tartagal, Província de Salta, Argentina, 1993

An American cutaneous leishmaniasis outbreak, with cases clustering during 1993 in Tartagal city, Salta, was reported. The outbreak involved 102 individuals, 43.1% of them with multiple ulcers. Age (mean: 33 years old) and sex distribution of cases (74.5% males), as well as working activity (70 forest-related), support the hypothesis of classical forest transmission leishmaniasis, despite the fact that the place of permanent residence was in periurban Tartagal. Moreover, during July, sandflies were only collected from one of the 'deforestation areas'. Lutzomyia intermedia was the single species of the 491 phlebotomines captured, reinforcing the vector incrimination of this species. Most infections must have been acquired during the fall (April to June), a pattern consistent with previous sandfly population dynamics data. Based on the epidemiological and entomological results, it was advised not to do any vector-targeted periurban control measures during July. Further studies should be done to assess if the high rate of multiple lesions was due to parasite factors or to infective vector density factors.Foi registrado um surto de leishmaniose cutânea americana, com casos agrupados na cidade de Tartagal, província de Salta, durante 1993. O surto envolveu 102 indivíduos, 43,1% deles com úlceras múltiplas. A idade (média: 33 anos) e distribuição de sexo nos casos (74,5% homens) como também a ocupação (70% relacionado com a floresta), apóia a hipótese da clássica transmissão de leishmaniose na floresta, apesar do fato de que o lugar de residência permanente estava na área periurbana de Tartagal. Além disso, durante julho, foram colecionados flebótomos só de uma área de desmatamento. Lutzomyia intermedia foi a única espécie dos 491 flebotomíneos capturados e reforça a incriminação de vetor desta espécie. A maioria das infecções deve ter sido adquirida durante o outono (abril para junho), um padrão consistente com dados prévios sob a dinâmica de população de flebótomos. Com base nos resultados, epidemiológicos e entomológicos foi aconselhado não fazer qualquer controle sobre vetores na área periurbana durante julho. Mais adiante deveriam ser feitos estudos para avaliar se a alta taxa de lesões múltiplas foi devido a fatores do parasita ou a fatores de densidade do vetor

Population parameters and nymphaea instars description of protortonia ecuadorensis (Hemiptera : Monophlebidae).

En Hemiptera, el infraorden Coccomorpha es considerado un taxón con gran potencial invasivo. En este contexto, se han observado infestaciones de Protortonia ecuadorensis (Hemiptera: Monophlebidae) sobre hospedantes arbóreos neotropicales de alto valor económico y ambiental en el área urbana de Tunja (Boyacá, Colombia). Objetivo. En el presente trabajo se analizaron algunos aspectos biológicos de esta especie, registrando atributos de su ciclo de vida, factores de mortalidad-fecundidad y descripción de sus instares ninfales en la zona de estudio. Metodología. El trabajo se realizó en condiciones de casa malla y laboratorio. Por una parte, ninfas de P. ecuadorensis provenientes de campo se establecieron y observaron sobre esquejes de S. humboldtiana en una estructura de madera, plástico y polisombra de 3,8 m3 bajo casa malla. Por otro lado, 120 huevos obtenidos se acondicionaron en laboratorio en recipientes de polipropileno, provistos con algodón, realizando observaciones y toma semanal de datos hasta la obtención de adultos. Resultados. A partir de las ninfas colectadas en campo, se registró un ciclo de vida univoltino de 301,8 ± 40,5 días (14,5°C; H.R: 72,5%; Fotoperiodo 12 horas), pasando por tres instares ninfales de 283,6 ± 32,4 días y longevidad estimada en 18,2 ± 8,1 días. El índice de mortalidad específico (qx ) calculado en la tabla de vida, se estimó para huevo en 0,24; ninfa I 0,17; ninfa II 0,47 y ninfa III 0,83. La tasa intrínseca de crecimiento per cápita (r= -0,63<0), al igual que el índice reproductivo neto Ro (0,798><1) indican una posible diapausa bajo condiciones de casa malla. Conclusión. De acuerdo con las curvas de supervivencia l x halladas en ninfa III (0,19) y hembra adulta (0,03), se recomienda aplicar agentes de control en estas etapas de mayor susceptibilidad.><0), al igual que el índice reproductivo neto Ro (0,798<1) > <1) indican una posible diapausa bajo condiciones de casa malla. Conclusión. De acuerdo con las curvas de supervivencia l x halladas en ninfa III (0,19) y hembra adulta (0,03), se recomienda aplicar agentes de control en estas etapas de mayor susceptibilidad.  In Hemiptera, Cocomorpha infraorder is considered a taxon with a high invasive potential. Regarding with this, the Protortonia ecuadorensis scale has been observed infesting neotropical arboreal hosts of high economic and environmental value at the urban area of Tunja (Boyacá, Colombia). Objective. In this work some biological features of this scale specie were analized and observed, recording specific life cycle attributes, such as population dynamics, mortality-fecundity factors and a description of their nymphal instars in the studied place. Methodology. The work was conducted under a mesh house and laboratory conditions. In one hand, nymphs from the field were stablished on S. humboldtiana cuttings located in a 3,8 m3 wood, plastic and mesh structure into a mesh house. On the other hand, 120 eggs were conditioned in polipropilene dishes with wood. Weekly observations and data collection were done util adult emergence. Results. From the nymphs collected in the field, a 301,8 ± 40,5 days univoltine life cycle was registered (14.5°C, RH: 72.5; 12 hours photoperiod), with three nymphal stages of 283,6 ± 32,4 days and 18,2 ± 8,1 days estimated longevity. The specific mortality rate (qx ) calculated in the life table by cohorts, was estimated for egg in 0.24; nymph I 0, 17, nymph II 0,47 and nymph III 0,83. The intrinsic per capite growth rate (r= -0, 63<0), as well as the net reproductive index Ro (0,798><1) indicate a possible diapause under hoop house. Conclusion. According to the survival curves (lx) found in nymph III (0,19) and adult female (0,03), the application of control agents in these susceptible stages is recommended.> <0), as well as the net reproductive index Ro (0,798 <1) indicate a possible diapause under hoop house. Conclusion. According to the survival curves (lx) found in nymph III (0,19) and adult female (0,03), the application of control agents in these susceptible stages is recommended

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

Conceptualizing and measuring distance in international business research:Recurring questions and best practice guidelines

Distance is a central concept in international business research, yet there is debate about the construct as well as its operationalization. In this editorial, we address three of the most important recurring questions posed by authors, editors, and reviewers by examining the theory, methods, and data of distance research. We discuss (1) how to theorize on distance, and (2) what method and (3) what data to use when constructing a distance index. We develop practical recommendations grounded in theory, illustrating and supporting them by calculating cross-country distance indices for all available country pairs and two of the most used distance indices: cultural and institutional. We show that, whereas a specific method to calculate distance may matter to some extent, the choice for a specific cultural or institutional framework to measure cultural or institutional distance has a major impact on country-pair distances. Overall, this editorial highlights the importance of matching data and method to the theoretical argument.</p

A Critical Tryptophan and Ca2+ in Activation and Catalysis of TPPI, the Enzyme Deficient in Classic Late-Infantile Neuronal Ceroid Lipofuscinosis

Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+).Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme.NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI.We propose that W542 and Ca(2+) are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis

Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?

BACKGROUND. Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS. We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon α (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon α and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE. These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.Scleroderma Research Foundatio

Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (∼2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ∼90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes

ELF5 drives lung metastasis in luminal breast cancer through recruitment of Gr1+ CD11b+ myeloid-derived suppressor cells

During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis–free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer