Non-Centered Spike-Triggered Covariance Analysis Reveals Neurotrophin-3 as a Developmental Regulator of Receptive Field Properties of ON-OFF Retinal Ganglion Cells

The functional separation of ON and OFF pathways, one of the fundamental features of the visual system, starts in the retina. During postnatal development, some retinal ganglion cells (RGCs) whose dendrites arborize in both ON and OFF sublaminae of the inner plexiform layer transform into RGCs with dendrites that monostratify in either the ON or OFF sublamina, acquiring final dendritic morphology in a subtype-dependent manner. Little is known about how the receptive field (RF) properties of ON, OFF, and ON-OFF RGCs mature during this time because of the lack of a reliable and efficient method to classify RGCs into these subtypes. To address this deficiency, we developed an innovative variant of Spike Triggered Covariance (STC) analysis, which we term Spike Triggered Covariance – Non-Centered (STC-NC) analysis. Using a multi-electrode array (MEA), we recorded the responses of a large population of mouse RGCs to a Gaussian white noise stimulus. As expected, the Spike-Triggered Average (STA) fails to identify responses driven by symmetric static nonlinearities such as those that underlie ON-OFF center RGC behavior. The STC-NC technique, in contrast, provides an efficient means to identify ON-OFF responses and quantify their RF center sizes accurately. Using this new tool, we find that RGCs gradually develop sensitivity to focal stimulation after eye opening, that the percentage of ON-OFF center cells decreases with age, and that RF centers of ON and ON-OFF cells become smaller. Importantly, we demonstrate for the first time that neurotrophin-3 (NT-3) regulates the development of physiological properties of ON-OFF center RGCs. Overexpression of NT-3 leads to the precocious maturation of RGC responsiveness and accelerates the developmental decrease of RF center size in ON-OFF cells. In summary, our study introduces STC-NC analysis which successfully identifies subtype RGCs and demonstrates how RF development relates to a neurotrophic driver in the retina

The role of nutrition in integrated programs to control neglected tropical diseases

There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs). Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment - the major strategy currently proposed to control several diseases - is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large-scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing NTDs in populations, and to restoring their health

Effects of Marine Reserves versus Nursery Habitat Availability on Structure of Reef Fish Communities

No-take marine fishery reserves sustain commercial stocks by acting as buffers against overexploitation and enhancing fishery catches in adjacent areas through spillover. Likewise, nursery habitats such as mangroves enhance populations of some species in adjacent habitats. However, there is lack of understanding of the magnitude of stock enhancement and the effects on community structure when both protection from fishing and access to nurseries concurrently act as drivers of fish population dynamics. In this study we test the separate as well as interactive effects of marine reserves and nursery habitat proximity on structure and abundance of coral reef fish communities. Reserves had no effect on fish community composition, while proximity to nursery habitat only had a significant effect on community structure of species that use mangroves or seagrass beds as nurseries. In terms of reef fish biomass, proximity to nursery habitat by far outweighed (biomass 249% higher than that in areas with no nursery access) the effects of protection from fishing in reserves (biomass 21% lower than non-reserve areas) for small nursery fish (≤25 cm total length). For large-bodied individuals of nursery species (>25 cm total length), an additive effect was present for these two factors, although fish benefited more from fishing protection (203% higher biomass) than from proximity to nurseries (139% higher). The magnitude of elevated biomass for small fish on coral reefs due to proximity to nurseries was such that nursery habitats seem able to overrule the usually positive effects on fish biomass by reef reserves. As a result, conservation of nursery habitats gains importance and more consideration should be given to the ecological processes that occur along nursery-reef boundaries that connect neighboring ecosystems

The Role of the Novel Exopolyphosphatase MT0516 in Mycobacterium tuberculosis Drug Tolerance and Persistence

Inorganic polyphosphate (poly P) has been postulated to play a regulatory role in the transition to bacterial persistence. In bacteria, poly P balance in the cell is maintained by the hydrolysis activity of the exopolyphosphatase PPX. However, the Mycobacterium tuberculosis PPX has not been characterized previously. Here we show that recombinant MT0516 hydrolyzes poly P, and an MT0516-deficient M. tuberculosis mutant exhibits elevated intracellular levels of poly P and increased expression of the genes mprB, sigE, and rel relative to the isogenic wild-type strain, indicating poly P-mediated signaling. Deficiency of MT0516 resulted in decelerated growth during logarithmic-phase in axenic cultures, and tolerance to the cell wall-active drug isoniazid. The MT0516-deficient mutant showed a significant survival defect in activated human macrophages and reduced persistence in the lungs of guinea pigs. We conclude that exopolyphosphatase is required for long-term survival of M. tuberculosis in necrotic lung lesions

A Research Agenda for Helminth Diseases of Humans: Social Ecology, Environmental Determinants, and Health Systems

In this paper, the Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), with the mandate to review helminthiases research and identify research priorities and gaps, focuses on the environmental, social, behavioural, and political determinants of human helminth infections and outlines a research and development agenda for the socioeconomic and health systems research required for the development of sustainable control programmes. Using Stockols' social-ecological approach, we describe the role of various social (poverty, policy, stigma, culture, and migration) and environmental determinants (the home environment, water resources development, and climate change) in the perpetuation of helminthic diseases, as well as their impact as contextual factors on health promotion interventions through both the regular and community-based health systems. We examine these interactions in regard to community participation, intersectoral collaboration, gender, and possibilities for upscaling helminthic disease control and elimination programmes within the context of integrated and interdisciplinary approaches. The research agenda summarises major gaps that need to be addressed

Changing Patterns of Microhabitat Utilization by the Threespot Damselfish, Stegastes planifrons, on Caribbean Reefs

Background: The threespot damselfish, Stegastes planifrons (Cuvier), is important in mediating interactions among corals, algae, and herbivores on Caribbean coral reefs. The preferred microhabitat of S. planifrons is thickets of the branching staghorn coral Acropora cervicornis. Within the past few decades, mass mortality of A. cervicornis from white-band disease and other factors has rendered this coral a minor ecological component throughout most of its range. Methodology/Principal Findings: Survey data from Jamaica (heavily fished), Florida and the Bahamas (moderately fished), the Cayman Islands (lightly to moderately fished), and Belize (lightly fished) indicate that distributional patterns of S. planifrons are positively correlated with live coral cover and topographic complexity. Our results suggest that speciesspecific microhabitat preferences and the availability of topographically complex microhabitats are more important than the abundance of predatory fish as proximal controls on S. planifrons distribution and abundance. Conclusions/Significance: The loss of the primary microhabitat of S. planifrons—A. cervicornis—has forced a shift in the distribution and recruitment of these damselfish onto remaining high-structured corals, especially the Montastraea annulari