Molecular epidemiology and diagnosis of "Mycobacterium bovis" infections in African cattle

Mycobacterium bovis is the major causative agent of bovine tuberculosis (BTB) and part of the Mycobacterium tuberculosis complex (MTBC). BTB can have an impact on the national and international economy, affects the ecosystem via transmission to wildlife and is of public health concern due to its zoonotic potential. Although still present in some industrialized countries, BTB today mostly affects developing countries lacking the resources to apply expensive test and slaughter schemes. In Africa, the disease is present virtually on the whole continent; however, little accurate information on its distribution and prevalence is available. Evaluations of antemortem tests for the diagnosis of BTB in Africa are scarce but a prerequisite to identify appropriate tools for future disease control programs. Spoligotyping and variable number of tandem repeat (VNTR) typing of M. bovis strains isolated from cattle in the UK has revealed the predominance of a single clonal complex of strains with subtypes of the complex being geographically localized to specific regions within the country. Spoligotype patterns of strains isolated from cattle from several countries throughout the world have been reported in a number of recent studies and the construction of databases (www.Mbovis.org, SPOLDB4) has facilitated their comparison and helped elucidate the distribution of specific strain families. In an attempt to gain insights into the population structure of M. bovis in Africa, we have isolated strains of M. bovis from cattle carcasses with gross visible lesions at abattoirs in Dakar (Senegal), Bamako (Mali), Sarh (Chad), Morogoro (Tanzania), Algiers (Algeria) and Blida (Algeria). These mycobacteria were subjected to spoligotyping and VNTR typing. A specific region of difference, which we have named RDAf1, was previously found to be absent in strains from Chad and presence of this deletion was assessed in our strain collection by PCR. In collaboration with others, additional strains of M. bovis from other African countries were subjected to molecular typing. At the abattoir of Sarh in Chad, 954 cattle were subjected to single intra-dermal comparative cervical tuberculin (SICCT) testing and two recently developed fluorescence polarization assays (FPA) prior to slaughter. Animal carcasses underwent standard meat inspection. Gross visible lesions were extracted, analyzed by microscopy and cultured. Cultured acid-fast bacilli (AFB) were further characterized by molecular techniques. The different diagnostic tests were evaluated using a sub-population of animals with either a PCR confirmed MTBC infection or no visible lesions. In addition, a Bayesian model for the evaluation of multiple diagnostic tests in the absence of a gold standard method was developed. In collaboration with others, we have identified a clonal complex of strains of M. bovis present at high frequency in cattle in population samples from Chad, Cameroon, Nigeria and Mali. This closely related group of bacteria is defined by the RDAf1 chromosomal deletion and can be identified by the absence of spacer 30 in its spoligotype pattern. We have named this group of strains the Bovis African1 (Af1) clonal complex. Strains of the Af1 clonal complex were not detected in population samples from other regions in Africa or other parts of the world, suggesting that the Af1 clonal complex is geographically localized to sub-Saharan West-Central Africa. VNTR typing allowed to distinguish sub-populations of the Af1 clonal complex, which were geographically localized to different countries. This was an unexpected result suggesting that the movement of strains between countries is not common in this area. In Mali, in addition to Af1, a second clonal group of M. bovis has been detected and matching VNTR patterns for some of its strains and strains from France could indicate a French origin. In Tanzania, also two clonal complexes of M. bovis were detected by spoligotyping with one clade showing a link to strains, previously identified in Uganda and Ethiopia and the second clade showing a link to strains previously isolated in South Africa. M. bovis strains isolated from Algerian cattle were closely related to strains from continental Europe and especially France. In conclusion, our work has revealed important insights into the population structure of M. bovis in Africa and suggests the presence of distinct clonal complexes of strains, geographically localized to specific areas of the continent. Our Bayesian model estimated the true BTB prevalence amongst the slaughterhouse cattle population in Sarh, Chad to be at 8%. The Bayesian and the gold standard test evaluation methods indicated that the ideal cut-off for positive SICCT test interpretation should be lowered from > 4 mm (OIE standard cut-off) to > 2 mm, in the Chadian setting. This result is of practical relevance and likely to apply to other countries in sub-Saharan Africa. Using this cut-off, sensitivity and specificity of SICCT was estimated at around 65% and 90%, respectively. Both FPA tests showed a sensitivity of less than 50% but specificities of at least 90%. Our results suggested that a substantial amount of lesions detected at the abattoir have been caused by other organisms than M. bovis

Early Cognitive/Social Deficits and Late Motor Phenotype in Conditional Wild-Type TDP-43 Transgenic Mice

Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate in depth the behavioral phenotype associated with this proteinopathy, we used as a model transgenic (Tg) mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. We previously characterized these mice at the neuropathological level and found progressive neurodegeneration and other features that evoke human TDP-43 proteinopathies of the FTD/ALS spectrum. In the present study we analyzed the behavior of mice at multiple domains, including motor, social and cognitive performance. Our results indicate that young hTDP-43-WT Tg mice (1 month after post-weaning transgene induction) present a normal motor phenotype compared to control littermates, as assessed by accelerated rotarod performance, spontaneous locomotor activity in the open field test and a mild degree of spasticity shown by a clasping phenotype. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory (Y-maze test) and recognition memory (novel object recognition test) in the absence of overt motor abnormalities. To investigate if the motor phenotype worsen with age, we analyzed the behavior of mice after long-term (up to 12 months) transgene induction. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hyperlocomotion in the open field test. In sum, these results demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT Tg mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary animal model for studying TDP-43 proteinopathies.Fil: Alfieri, Julio Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Silva Pinto, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Müller Igaz, Lionel Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Quantifying the Impact of Women’s Participation in Post-Conflict Economic Recovery

There is still a considerable lack of systematic and rigorous understanding about the impact of violent conflict on women‘s roles, activities and aspirations, or about the nature and magnitude of the benefits of including women more fully in economic recovery and peace-building processes. Policy programming around gender issues in post-conflict contexts is currently being designed based on limited rigorous evidence, and incorporates inadequate procedures to evaluate its impact in terms of gender roles and gender equality. This situation has at times resulted in misplaced interventions and the continued emphasis on the reintegration of (male) combatants, and male employment generation programmes. The main aim of this report is to analyse how changes in the roles and activities of women during episodes of violent conflict may shape their contribution to post-conflict economic recovery and sustainable peace. The report poses two important questions for which limited evidence is to date available in the academic literature on violent conflict or in policy programming in post-conflict contexts: 1) How does violent conflict change the roles that women take on within their households and communities? 2) How do changes in female roles during conflict affect women‘s own status after the conflict, and the capacity of households and communities to recover from the conflict?UN Wome

Where to Go on Your Next Trip? Optimizing Travel Destinations Based on User Preferences

Recommendation based on user preferences is a common task for e-commerce websites. New recommendation algorithms are often evaluated by offline comparison to baseline algorithms such as recommending random or the most popular items. Here, we investigate how these algorithms themselves perform and compare to the operational production system in large scale online experiments in a real-world application. Specifically, we focus on recommending travel destinations at Booking.com, a major online travel site, to users searching for their preferred vacation activities. To build ranking models we use multi-criteria rating data provided by previous users after their stay at a destination. We implement three methods and compare them to the current baseline in Booking.com: random, most popular, and Naive Bayes. Our general conclusion is that, in an online A/B test with live users, our Naive-Bayes based ranker increased user engagement significantly over the current online system.Comment: 6 pages, 2 figures in SIGIR 2015, SIRIP Symposium on IR in Practic

Platelet lysate as a serum substitute for 2D static and 3D perfusion culture of stromal vascular fraction cells from human adipose tissue

Fetal bovine serum (FBS) and fibroblast growth factor (FGF)-2 are key supplements for the culture of stromal vascular fraction (SVF) cells from adipose tissue, both for typical monolayer (2D) expansion and for streamlined generation of osteogenic-vasculogenic grafts in 3D perfusion culture. The present study investigates whether factors present in human platelet lysate (PL) could substitute for FBS and FGF-2 in 2D and 3D culture models of SVF cells from human lipoaspirates. SVF cells were grown in medium supplemented with 10% FBS+FGF-2 or with 5% PL. In 2D cultures, PL initially supported SVF cell proliferation, but resulted in growth arrest shortly after the first passage. Freshly isolated SVF cells cultured with both media under perfusion for 5 days within 3D ceramic scaffolds induced bone formation after subcutaneous implantation in nude mice. However, blood vessels of donor origin were generated only using FBS+FGF-2-cultured cells. This was unexpected, because the proportion of CD34+/CD31+ endothelial lineage cells was significantly higher with PL than that of FBS+FGF-2 (33% vs. 3%, respectively). These results support the use of PL as a substitute of FBS+FGF-2 for short-term culture of human SVF cells, and indicate that more specific serum-free formulations are required to maintain a functionally vasculogenic fraction of SVF cells expanded under 3D perfusion

Using multiobjective optimization to reconstruct interferometric data (II): polarimetry and time dynamics

In Very Long Baseline Interferometry (VLBI), signals from multiple antennas combine to create a sparsely sampled virtual aperture, its effective diameter determined by the largest antenna separation. The inherent sparsity makes VLBI imaging an ill-posed inverse problem, prompting the use of algorithms like the Multiobjective Evolutionary Algorithm by Decomposition (MOEA/D), as proposed in the first paper of this series. This study focuses on extending MOEA/D to polarimetric and time dynamic reconstructions, particularly relevant for the VLBI community and the Event Horizon Telescope Collaboration (EHTC). MOEA/D's success in providing a unique, fast, and largely unsupervised representation of image structure serves as the basis for exploring these extensions. The extension involves incorporating penalty terms specific to total intensity imaging, time-variable, and polarimetric variants within MOEA/D's multiobjective, evolutionary framework. The Pareto front, representing non-dominated solutions, is computed, revealing clusters of proximities. Testing MOEA/D with synthetic datasets representative of EHTC's main targets demonstrates successful recovery of polarimetric and time-dynamic signatures despite sparsity and realistic data corruptions. MOEA/D's extension proves effective in the anticipated EHTC setting, offering an alternative and independent claim to existing methods. It not only explores the problem globally but also eliminates the need for parameter surveys, distinguishing it from Regularized Maximum Likelihood (RML) methods. MOEA/D emerges as a novel and useful tool for robustly characterizing polarimetric and dynamic signatures in VLBI datasets with minimal user-based choices. Future work aims to address the last remaining limitation of MOEA/D, specifically regarding the number of pixels and numerical performance, to establish it within the VLBI data reduction pipeline.Comment: Both first authors have contributed equally to this work. To appear in A&

Movimentos sociais e suas relações com o(s) estado(s) nos 30 anos do orçamento participativo de Porto Alegre: análise em duas regiões com tradições associativas distintas

A presente pesquisa buscou analisar dez movimentos sociais e suas relações com o(s) Estado(s), em duas regiões de tradição associativa distinta, através da interação em uma Instituição Participativa (IP): O Orçamento Participativo (OP) de Porto Alegre. Nesse sentido, foram estudados cinco movimentos sociais da Região da Lomba do Pinheiro, a qual possui longa tradição associativa na cidade; e, cinco movimentos sociais da Região Centro Sul, a qual teve seu associativismo induzido a partir do surgimento do OP no início da década de 1990. No que se refere a análise dos movimentos sociais, a pesquisa fez uso do conceito de Padrões de Ação Coletiva (PAC´s) (CARLOS, 2012a) para examinar três dimensões distintas e interligadas: organizacional, relacional e discursiva. Para tanto, o estudo utilizou-se de pesquisa documental, observação de campo e entrevistas. Já a interação dos movimentos sociais para com o(s) Estado(s) foi estudada em conjunto com seus PAC´s através da análise dos encaixes institucionais desses movimentos nos cargos de delegados e conselheiros do(s) OP(s) e de possíveis ações autônomas (OLIVEIRA; DOWBOR, 2020) presentes nas diferentes relações com esse(s) Estado(s). Foi por amparar-se no conceito de Estado democrático mutável que a pesquisa caracterizou, adaptando-se os conceitos trazidos por Tilly (2013), os diferentes Estado(s) ou diferentes OP(s), a depender dos níveis democráticos dispostos nessa IP. No caso do OP de Porto Alegre, a investigação indicou dois períodos distintos: primeiramente, um de democratização, denominado “período de criação e consolidação”, que se estende de 1989 até 2001, e segundo um de OP desdemocratizado, chamado de “período de crise e limites”, que se inicia em 2002 e segue até 2019, momento em que o OP completara seus 30 anos de existência. As hipóteses do estudo sugeriam que regiões com tradição associativa de mais longa data e formada a partir de matrizes discursivas e identidades calcadas nas reivindicações por direitos, teriam tendência a apresentar movimentos sociais com Padrões de Ação Coletiva (PAC´s) e tipos de interações diferenciadas com os OP(s) quando comparados com regiões de menor tradição associativa, ou com associativismo induzido a partir do surgimento do OP. No que se refere aos tipos de interações diferenciadas, a sugestão seria a de que territórios com longa tradição associativa tenderiam a apresentar, mais frequentemente, movimentos sociais expressando ações de autonomia (OLIVEIRA; DOWBOR, 2020) nas relações com os diferentes Estado(s) ou OP(s). Nesse direcionamento, a pesquisa propôs uma comparação entre os casos (cross-case) de uma mesma região e comparação entre os casos (cross-case) de regiões com tradição associativa distinta. As análises confirmaram as hipóteses levantadas, percebendo um “padrão” diferenciado nos PAC´s dos movimentos sociais da Região da Lomba do Pinheiro, que em grande maioria combinaram ações de contenção e cooperação com os diferentes Estado(s) e apresentaram diferenças peculiares em suas redes de relações e identidades. Outrossim, a pesquisa mostrou que a região sem tradição associativa passou por um processo ainda maior de desdemocratização do OP, tendo em conjunto, uma ampliação das práticas clientelistas por parte dos partidos governantes durante o “período de crise e limites” dessa IP.This research aimed to analyze ten social movements and their relations with State(s) on two distinct tradition regions associative, through interaction in a participatory institution (PI): the Porto Alegre's Participatory Budgeting (PB). In this way, five social movements from Lomba do Pinheiros' region, which has a long associative tradition within the city, and five social movements from the Centro Sul region, which had their associativism induced by the upcoming of PB in the early 1990s. Referring to the analysis of the social movements, this research used the concept of Patterns of Collective Action (PACs) (CARLOS, 2012) in order to examine three distinct and interconnected dimensions: organizational, relations, and discursive. For that, this study utilized documentary research, field observation, and interviews. The social movement interaction with the State was studied together with PACs through the analysis of engineering fit of those social movements' on positions delegates, in council of PB and the possibility of autonomy actions (OLIVEIRA, DOWBOR, 2020) presents in different relationships with these State(s). It was based on the concept of a mutable democratic State that the research characterized, adapting the concepts brought by Tilly (2013), the different State(s) or different OP(s), depending on the democratic levels arranged in this PI. In the case of Porto Alegre's PB, this investigation indicated two distinct periods: the first one would be a democratization period, called the "creation and consolidation period", that extends from 1989 until 2001 and, the second, de-democratization OP period, called "crisis and limitation period", that extends from 2002 until 2019, when the PB completes 30 years of existence. The hypothesis of this study suggested that regions with long term associative traditions and with discursive matrices and right claiming identities would have a trend to show social movements with Patterns of Collective Action (PAC) differents and distinct kind of interaction with PB, when compared to territories with smaller associative tradition, or with associativism induced by the upcoming of PB. Regarding the kind of differentiating interactions, the suggestion would be that long-term associative tradition territories would tend to show more frequently social movements expressing autonomy actions (OLIVEIRA; DOWBOR, 2020) in relation the different State(s) or PB(s). In this direction, the research proposed a comparison between the cases (cross-case) of the same region and comparison between the cases (cross-case) of regions with different associative tradition. The analyzes confirmed the hypotheses raised, perceiving a different "pattern" in the PACs of the social movements of the Lomba do Pinheiro Region, which for the most part combined contention and cooperation actions with the different State(s) and presented peculiar differences in their relations networks and identities. Furthermore, the research showed that the region without associative tradition went through an even greater process of dedemocratization of the PB, having together, an expansion of clientelistic practices by the ruling parties during the “period of crisis and limits” of this IP

Reversible behavioral phenotypes in a conditional mouse model of TDP-43 proteinopathies

Transactive response DNA-binding protein 43 (TDP-43) mislocalization and aggregation are hallmark features of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). We have previously shown in mice that inducible overexpression of a cytoplasmically localized form of TDP-43 (TDP-43-ΔNLS) in forebrain neurons evokes neuropathological changes that recapitulate several features of TDP-43 proteinopathies. Detailed behavioral phenotyping could provide further validation for its usage as a model for FTD. In the present study, we performed a battery of behavioral tests to evaluate motor, cognitive, and social phenotypes in this model. We found that transgene (Tg) induction by doxycycline removal at weaning led to motor abnormalities including hyperlocomotion in the open field test, impaired coordination and balance in the rotarod test, and increased spasticity as shown by a clasping phenotype. Cognitive assessment demonstrated impaired recognition and spatial memory, measured by novel object recognition and Y-maze tests. Remarkably, TDP-43-ΔNLS mice displayed deficits in social behavior, mimicking a key aspect of FTD. To determine whether these symptoms were reversible, we suppressed Tg expression for 14 d in 1.5-month-old mice showing an established behavioral phenotype but modest neurodegeneration and found that motor and cognitive deficits were ameliorated; however, social performance remained altered. When Tg expression was suppressed in 6.5-month-old mice showing overt neurodegeneration, motor deficits were irreversible. These results indicate that TDP-43-ΔNLS mice display several core behavioral features of FTD with motor neuron disease, possibly due to functional changes in surviving neurons, and might serve as a valuable tool to unveil the underlying mechanisms of this and other TDP-43 proteinopathies.Fil: Alfieri, Julio Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Pino, Natalia S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Müller Igaz, Lionel Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Data-based system representations from irregularly measured data

Non-parametric representations of dynamical systems based on the image of a Hankel matrix of data are extensively used for data-driven control. However, if samples of data are missing, obtaining such representations becomes a difficult task. By exploiting the kernel structure of Hankel matrices of irregularly measured data generated by a linear time-invariant system, we provide computational methods for which any complete finite-length behavior of the system can be obtained. For the special case of periodically missing outputs, we provide conditions on the input such that the former result is guaranteed. We illustrate with an example how the resulting representation provides a more computationally efficient method for low-rank matrix completion when compared to an alternative method.Comment: submitted to IEEE Transactions on Automatic Contro