Somatic growth dynamics of West Atlantic hawksbill sea turtles: a spatio-temporal perspective

This is the final version of the article. Available from the publisher via the DOI in this record.Somatic growth dynamics are an integrated response to environmental conditions. Hawksbill sea turtles (Eretmochelys imbricata) are long-lived, major consumers in coral reef habitats that move over broad geographic areas (hundreds to thousands of kilometers). We evaluated spatio-temporal effects on hawksbill growth dynamics over a 33-yr period and 24 study sites throughout the West Atlantic and explored relationships between growth dynamics and climate indices. We compiled the largest ever data set on somatic growth rates for hawksbills – 3541 growth increments from 1980 to 2013. Using generalized additive mixed model analyses, we evaluated 10 covariates, including spatial and temporal variation, that could affect growth rates. Growth rates throughout the region responded similarly over space and time. The lack of a spatial effect or spatio-temporal interaction and the very strong temporal effect reveal that growth rates in West Atlantic hawksbills are likely driven by region-wide forces. Between 1997 and 2013, mean growth rates declined significantly and steadily by 18%. Regional climate indices have significant relationships with annual growth rates with 0- or 1-yr lags: positive with the Multivariate El Niño Southern Oscillation Index (correlation = 0.99) and negative with Caribbean sea surface temperature (correlation = −0.85). Declines in growth rates between 1997 and 2013 throughout the West Atlantic most likely resulted from warming waters through indirect negative effects on foraging resources of hawksbills. These climatic influences are complex. With increasing temperatures, trajectories of decline of coral cover and availability in reef habitats of major prey species of hawksbills are not parallel. Knowledge of how choice of foraging habitats, prey selection, and prey abundance are affected by warming water temperatures is needed to understand how climate change will affect productivity of consumers that live in association with coral reefs

Let’s not forget tautomers

A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments

Synchrotron radiography studies of shear-induced dilation in semi-solid Al alloys and steels

An improved understanding of the response of solidifying microstructures to load is required to further minimize casting defects and optimize casting processes. This article overviews synchrotron radiography studies that directly measure the micromechanics of semisolid alloy deformation in a thin sample direct-shear cell. It is shown that shear-induced dilation (also known as Reynolds’ dilatancy) occurs in semisolid alloys with morphologies ranging from equiaxed-dendritic to globular, at solid fractions from the dendrite coherency point to ~90% solid, and it occurs in both Al alloys and carbon steels. Discrete-element method simulations that treat solidifying microstructures as granular materials are then used to explore the origins of dilatancy in semisolid alloys

Global Conservation Priorities for Marine Turtles

Where conservation resources are limited and conservation targets are diverse, robust yet flexible priority-setting frameworks are vital. Priority-setting is especially important for geographically widespread species with distinct populations subject to multiple threats that operate on different spatial and temporal scales. Marine turtles are widely distributed and exhibit intra-specific variations in population sizes and trends, as well as reproduction and morphology. However, current global extinction risk assessment frameworks do not assess conservation status of spatially and biologically distinct marine turtle Regional Management Units (RMUs), and thus do not capture variations in population trends, impacts of threats, or necessary conservation actions across individual populations. To address this issue, we developed a new assessment framework that allowed us to evaluate, compare and organize marine turtle RMUs according to status and threats criteria. Because conservation priorities can vary widely (i.e. from avoiding imminent extinction to maintaining long-term monitoring efforts) we developed a “conservation priorities portfolio” system using categories of paired risk and threats scores for all RMUs (n = 58). We performed these assessments and rankings globally, by species, by ocean basin, and by recognized geopolitical bodies to identify patterns in risk, threats, and data gaps at different scales. This process resulted in characterization of risk and threats to all marine turtle RMUs, including identification of the world's 11 most endangered marine turtle RMUs based on highest risk and threats scores. This system also highlighted important gaps in available information that is crucial for accurate conservation assessments. Overall, this priority-setting framework can provide guidance for research and conservation priorities at multiple relevant scales, and should serve as a model for conservation status assessments and priority-setting for widespread, long-lived taxa

Identification of Host Cytosolic Sensors and Bacterial Factors Regulating the Type I Interferon Response to Legionella pneumophila

Legionella pneumophila is a gram-negative bacterial pathogen that replicates in host macrophages and causes a severe pneumonia called Legionnaires' Disease. The innate immune response to L. pneumophila remains poorly understood. Here we focused on identifying host and bacterial factors involved in the production of type I interferons (IFN) in response to L. pneumophila. It was previously suggested that the delivery of L. pneumophila DNA to the host cell cytosol is the primary signal that induces the type I IFN response. However, our data are not easily reconciled with this model. We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila. Importantly, these sensors do not seem to be required for the IFN response to L. pneumophila DNA, whereas we found that RIG-I was required for the response to L. pneumophila RNA. Thus, we hypothesize that bacterial RNA, or perhaps an induced host RNA, is the primary stimulus inducing the IFN response to L. pneumophila. Our study also identified a secreted effector protein, SdhA, as a key suppressor of the IFN response to L. pneumophila. Although viral suppressors of cytosolic RNA-sensing pathways have been previously identified, analogous bacterial factors have not been described. Thus, our results provide new insights into the molecular mechanisms by which an intracellular bacterial pathogen activates and also represses innate immune responses

Peripheral administration of lactate produces antidepressant-like effects.

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

Background: Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques - including site-based monitoring, genetic analyses, mark-recapture studies and telemetry - can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings: To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine-to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance: The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework - including maps and supporting metadata - will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis

Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis.

Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities

Globular cluster systems and galaxy formation

Globular clusters are compact, gravitationally bound systems of up to a million stars. The GCs in the Milky Way contain some of the oldest stars known, and provide important clues to the early formation and continuing evolution of our Galaxy. More generally, GCs are associated with galaxies of all types and masses, from low-mass dwarf galaxies to the most massive early-type galaxies which lie in the centres of massive galaxy clusters. GC systems show several properties which connect tightly with properties of their host galaxies. For example, the total mass of GCs in a system scales linearly with the dark matter halo mass of its host galaxy. Numerical simulations are at the point of being able to resolve globular cluster formation within a cosmological framework. Therefore, GCs link a range of scales, from the physics of star formation in turbulent gas clouds, to the large-scale properties of galaxies and their dark matter. In this Chapter we review some of the basic observational approaches for GC systems, some of their key observational properties, and describe how GCs provide important clues to the formation of their parent galaxies.Comment: 32 pages, 6 figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics