Retracing micro-epidemics of Chagas disease using epicenter regression

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al espa?ol disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.     

Preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals: strategy,challenges, current practices

Evaluation of pharmaceutical agents in children is now conducted earlier in the drug development process. An important consideration for this pediatric use is how to assess and support its safety. This article is a collaborative effort of industry toxicologists to review strategies, challenges, and current practice regarding preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals. Biopharmaceuticals include a diverse group of molecular, cell‐based or gene therapeutics derived from biological sources or complex biotechnological processes. The principles of preclinical support of pediatric drug development for biopharmaceuticals are similar to those for small molecule pharmaceuticals and in general follow the same regulatory guidances outlined by the Food and Drug Administration and European Medicines Agency. However, many biopharmaceuticals are also inherently different, with limited species specificity or immunogenic potential which may impact the approach taken. This article discusses several key areas to aid in the support of pediatric clinical use, study design considerations for juvenile toxicity studies when they are needed, and current practices to support pediatric drug development based on surveys specifically targeting biopharmaceutical development. Birth Defects Res (Part B) 92:359–380, 2011. © 2011 Wiley‐Liss, Inc.     

Architecture and development of the Neurospora crassa hypha -- a model cell for polarized growth

Neurospora crassa has been at the forefront of biological research from the early days of biochemical genetics to current progress being made in understanding gene and genetic network function. Here, we discuss recent developments in analysis of the fundamental form of fungal growth, development and proliferation -- the hypha. Understanding the establishment and maintenance of polarity, hyphal elongation, septation, branching and differentiation are at the core of current research. The advances in the identification and functional dissection of regulatory as well as structural components of the hypha provide an expanding basis for elucidation of fundamental attributes of the fungal cell. The availability and continuous development of various molecular and microscopic tools, as utilized by an active and co-supportive research community, promises to yield additional important new discoveries on the biology of fungi.     

Seasonal water availability predicts the relative abundance of C3 and C4 grasses in Australia

Aim Numerous studies have examined the climatic factors that influence the abundance of C₄ species within the grass flora (C₄ relative species richness) in various regions throughout the world, but very few have examined the relative abundance of C₄ vs. C₃ grasses (C₄ relative abundance). We sought to determine the climatic factors that influence C₄ relative abundance throughout Australia. Location Australia (including Tasmania). Methods We measured C₄ relative abundance at 168 locations and measured δ¹³C (the abundance of ¹³C relative to ¹²C) of the bone collagen of 779 kangaroos collected throughout Australia, as bone collagen δ¹³C was assumed to be proportional to the relative abundance of C₄ grasses in the diet. Results Both C₄ relative abundance and kangaroo bone collagen δ¹³C were found to have a strong positive relationship with seasonal water availability, i.e. the distribution of rainfall in the C₄ vs. C₃ growing seasons (76% and 69% of deviance explained, respectively). There was clear evidence that seasonal water availability was a better predictor of both C₄ relative abundance and bone collagen δ¹³C than other climate variables such as mean annual temperature and January daily minimum temperature. However, seasonal water availability appeared to be a relatively poor predictor of C₄ relative species richness, which was most closely related to January daily minimum temperature (90% of deviance explained). Main conclusions Our results highlight the relatively poor relationship between C₄ relative abundance and C₄ relative species richness, and suggest that these two variables may be related to different climatic factors. They also suggest that caution is required when using C₄ relative species richness to infer the relative biomass and productivity of C₄ grasses on a global scale.     

Prediction and assessment of the time-varying effective pulmonary vein area via cardiac MRI and Doppler echocardiography

Accurately estimating left atrial (LA) volume with Doppler echocardiography remains challenging. Using angiography for validation, Marino et al. (Marino P, Prioli AM, Destro G, LoSchiavo I, Golia G, and Zardini P. Am Heart J 127: 886-898, 1994) determined LA volume throughout the cardiac cycle by integrating the velocity-time integrals of Doppler transmitral and pulmonary venous flow, assuming constant mitral valve and pulmonary vein areas. However, this LA volume determination method has never been compared with three-dimensional LA volume data from cardiac MRI, the gold standard for cardiac chamber volume measurement. Previously, we determined that the effective mitral valve area is not constant but varies as a function of time. Therefore, we sought to determine whether the effective pulmonary vein area (EPVA) might be time varying as well and also assessed Marino's method for estimating LA volume. We imaged 10 normal subjects using cardiac MRI and concomitant transthoracic Doppler echocardiography. LA and left ventricular (LV) volumes were measured by MRI, transmitral and pulmonary vein flows were measured by Doppler echocardiography, and time dependence was synchronized via the electrocardiogram. LA volume, estimated using Marino's method, was compared with the MRI measurements. Differences were observed, and the discrepancy between the echocardiographic and MRI methods was used to predict EPVA as a function of time. EPVA was also directly measured from short-axis MRI images and was found to be time varying in concordance with predicted values. We conclude that because EPVA and LA volume time dependence are in phase, LA filling in systole and LV filling in diastole are both facilitated. Application to subjects in select pathophysiological states is in progress.     

A temporal approach to linking aboveground and belowground ecology

Ecologists are becoming increasingly aware of the role of aboveground-belowground relationships in controlling ecosystem processes and properties. Here, we review recent studies that show that relationships between aboveground and belowground communities operate over a hierarchy of temporal scales, ranging from days to seasons, to millennia, with differing consequences for ecosystem structure and function. We propose that a temporal framework is crucial to our understanding of the nature and ecological significance of relationships between aboveground and belowground communities.     

Cryo-electron microscopy of the giant Mimivirus

Mimivirus is the largest known virus. Using cryo-electron microscopy, the virus was shown to be icosahedral, covered by long fibers, and appears to have at least two lipid membranes within its protein capsid. A unique vertex, presumably for attachment and infection of the host, can be seen for particles that have a suitable orientation on the micrographs.