Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of Adult T-Cell Leukemia/Lymphoma (ATL), the Tropical Spastic Paraparesis/HTLV-1-associated Myelopathy (TSP/HAM) and other inflammatory diseases, including dermatitis, uveitis, and myositis. It is estimated that 2–8% of the infected persons will develop a HTLV-1-associated disease during their lifetimes, frequently TSP/HAM. Thus far, there is not a specific treatment to this progressive and chronic disease. HTLV-1 has means of three transmission: (i) from mother to child during prolonged breastfeeding, (ii) between sexual partners and (iii) through blood transfusion. HTLV-1 has been characterized in 7 subtypes and the geographical distribution and the clinical impact of this infection is not well known, mainly in African population. HTLV-1 is endemic in sub-Saharan Africa. Mozambique is a country of southeastern Africa where TSP/HAM cases were reported. Recently, our group estimated the HTLV prevalence among Mozambican blood donors as 0.9%. In this work we performed a genetic analysis of HTLV-1 in blood donors and HIV/HTLV co-infected patients from Maputo, Mozambique. Our results showed the presence of three HTLV-1 clusters within the Cosmopolitan/Transcontinental subtype/subgroup. The differential rates of HIV-1/HTLV-1 co-infection in the three HTLV-1 clusters demonstrated the dynamic of the two viruses and the need for implementation of control measures focusing on both retroviruses

The Inactivation Principle: Mathematical Solutions Minimizing the Absolute Work and Biological Implications for the Planning of Arm Movements

An important question in the literature focusing on motor control is to determine which laws drive biological limb movements. This question has prompted numerous investigations analyzing arm movements in both humans and monkeys. Many theories assume that among all possible movements the one actually performed satisfies an optimality criterion. In the framework of optimal control theory, a first approach is to choose a cost function and test whether the proposed model fits with experimental data. A second approach (generally considered as the more difficult) is to infer the cost function from behavioral data. The cost proposed here includes a term called the absolute work of forces, reflecting the mechanical energy expenditure. Contrary to most investigations studying optimality principles of arm movements, this model has the particularity of using a cost function that is not smooth. First, a mathematical theory related to both direct and inverse optimal control approaches is presented. The first theoretical result is the Inactivation Principle, according to which minimizing a term similar to the absolute work implies simultaneous inactivation of agonistic and antagonistic muscles acting on a single joint, near the time of peak velocity. The second theoretical result is that, conversely, the presence of non-smoothness in the cost function is a necessary condition for the existence of such inactivation. Second, during an experimental study, participants were asked to perform fast vertical arm movements with one, two, and three degrees of freedom. Observed trajectories, velocity profiles, and final postures were accurately simulated by the model. In accordance, electromyographic signals showed brief simultaneous inactivation of opposing muscles during movements. Thus, assuming that human movements are optimal with respect to a certain integral cost, the minimization of an absolute-work-like cost is supported by experimental observations. Such types of optimality criteria may be applied to a large range of biological movements

Deciphering the intracellular metabolism of Listeria monocytogenes by mutant screening and modelling

Background: The human pathogen Listeria monocytogenes resides and proliferates within the cytoplasm of epithelial cells. While the virulence factors essentially contributing to this step of the infection cycle are well characterized, the set of listerial genes contributing to intracellular replication remains to be defined on a genome-wide level. Results: A comprehensive library of L. monocytogenes strain EGD knockout mutants was constructed upon insertion-duplication mutagenesis, and 1491 mutants were tested for their phenotypes in rich medium and in a Caco-2 cell culture assay. Following sequencing of the plasmid insertion site, 141 different genes required for invasion of and replication in Caco-2 cells were identified. Ten in-frame deletion mutants were constructed that confirmed the data. The genes with known functions are mainly involved in cellular processes including transport, in the intermediary metabolism of sugars, nucleotides and lipids, and in information pathways such as regulatory functions. No function could be ascribed to 18 genes, and a counterpart of eight genes is missing in the apathogenic species L. innocua. Mice infection studies revealed the in vivo requirement of IspE (Lmo0190) involved in mevalonate synthesis, and of the novel ABC transporter Lmo0135-0137 associated with cysteine transport. Based on the data of this genome-scale screening, an extreme pathway and elementary mode analysis was applied that demonstrates the critical role of glycerol and purine metabolism, of fucose utilization, and of the synthesis of glutathione, aspartate semialdehyde, serine and branched chain amino acids during intracellular replication of L. monocytogenes. Conclusion: The combination of a genetic screening and a modelling approach revealed that a series of transporters help L. monocytogenes to overcome a putative lack of nutrients within cells, and that a high metabolic flexibility contributes to the intracellular replication of this pathogen

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.</p> <p>Methods</p> <p>The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.</p> <p>Results</p> <p>A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.</p> <p>Conclusions</p> <p>Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.</p

Evidence for Composite Cost Functions in Arm Movement Planning: An Inverse Optimal Control Approach

An important issue in motor control is understanding the basic principles underlying the accomplishment of natural movements. According to optimal control theory, the problem can be stated in these terms: what cost function do we optimize to coordinate the many more degrees of freedom than necessary to fulfill a specific motor goal? This question has not received a final answer yet, since what is optimized partly depends on the requirements of the task. Many cost functions were proposed in the past, and most of them were found to be in agreement with experimental data. Therefore, the actual principles on which the brain relies to achieve a certain motor behavior are still unclear. Existing results might suggest that movements are not the results of the minimization of single but rather of composite cost functions. In order to better clarify this last point, we consider an innovative experimental paradigm characterized by arm reaching with target redundancy. Within this framework, we make use of an inverse optimal control technique to automatically infer the (combination of) optimality criteria that best fit the experimental data. Results show that the subjects exhibited a consistent behavior during each experimental condition, even though the target point was not prescribed in advance. Inverse and direct optimal control together reveal that the average arm trajectories were best replicated when optimizing the combination of two cost functions, nominally a mix between the absolute work of torques and the integrated squared joint acceleration. Our results thus support the cost combination hypothesis and demonstrate that the recorded movements were closely linked to the combination of two complementary functions related to mechanical energy expenditure and joint-level smoothness

Fine-scale niche structure of Neotropical forests reflects a legacy of the Great American Biotic Interchange

The tendency of species to retain their ancestral niches may link processes that determine community assembly with biogeographic histories that span geological time scales. Biogeo- graphic history is likely to have had a particularly strong impact on Neotropical forests because of the influence of the Great American Biotic Interchange, which followed emergence of a land connection between North and South America B3Ma. Here we examine the community structure, ancestral niches and ancestral distributions of the related, hyperdiverse woody plant genera Psychotria and Palicourea (Rubiaceae) in Panama. We find that 49% of the variation in hydraulic traits, a strong determinant of community structure, is explained by species’ origins in climatically distinct biogeographic regions. Niche evolution models for a regional sample of 152 species indicate that ancestral climatic niches are associated with species’ habitat distributions, and hence local community structure and composition, even millions of years after dispersal into new geographic regions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99545/1/Sedioetal2013.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99545/2/Sedioetal2013suppl..pdf8

Product and process innovation in manufacturing firms: a 30-year bibliometric analysis

Built upon a thirty-year dataset collected from the Web of Science database, the present research aims to offer a comprehensive overview of papers, authors, streams of research, and the most influential journals that discuss product and process innovation in the manufacturing environment. The dataset is composed of 418 papers from more than 150 journals from the period between 1985 and 2015. Homogeneity analysis by means of alternating least squares (HOMALS) and Social Network Analysis (SNA) are used to accomplish the objectives listed above through the keywords given by authors. Initially, the paper highlights and discusses the similarity between the topics debated by the main journals in this field. Subsequently, a wide-range map of topics is presented highlighting five main areas of interests; namely, performance, patent, small firm, product development, and organization. A SNA is also performed in order to validate the results that emerged from HOMALS. Finally, several insights about future research avenues in the manufacturing field are provided

Do Humans Optimally Exploit Redundancy to Control Step Variability in Walking?

It is widely accepted that humans and animals minimize energetic cost while walking. While such principles predict average behavior, they do not explain the variability observed in walking. For robust performance, walking movements must adapt at each step, not just on average. Here, we propose an analytical framework that reconciles issues of optimality, redundancy, and stochasticity. For human treadmill walking, we defined a goal function to formulate a precise mathematical definition of one possible control strategy: maintain constant speed at each stride. We recorded stride times and stride lengths from healthy subjects walking at five speeds. The specified goal function yielded a decomposition of stride-to-stride variations into new gait variables explicitly related to achieving the hypothesized strategy. Subjects exhibited greatly decreased variability for goal-relevant gait fluctuations directly related to achieving this strategy, but far greater variability for goal-irrelevant fluctuations. More importantly, humans immediately corrected goal-relevant deviations at each successive stride, while allowing goal-irrelevant deviations to persist across multiple strides. To demonstrate that this was not the only strategy people could have used to successfully accomplish the task, we created three surrogate data sets. Each tested a specific alternative hypothesis that subjects used a different strategy that made no reference to the hypothesized goal function. Humans did not adopt any of these viable alternative strategies. Finally, we developed a sequence of stochastic control models of stride-to-stride variability for walking, based on the Minimum Intervention Principle. We demonstrate that healthy humans are not precisely “optimal,” but instead consistently slightly over-correct small deviations in walking speed at each stride. Our results reveal a new governing principle for regulating stride-to-stride fluctuations in human walking that acts independently of, but in parallel with, minimizing energetic cost. Thus, humans exploit task redundancies to achieve robust control while minimizing effort and allowing potentially beneficial motor variability