Mercury in Neotropical birds: a synthesis and prospectus on 13 years of exposure data.

Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics.

RESúMEN: La contaminación ambiental por mercurio (Hg) en los trópicos supera nuestra comprensión de sus consecuencias para la biodiversidad. Los vacíos de conocimiento que existen sobre la exposición a la contaminación podrían ocultar las amenazas para la conservación en el Neotrópico: una región que alberga a más de la mitad de las especies del mundo, pero que enfrenta una continua intensificación de las emisiones de Hg y del cambio de uso del suelo por el avance de la minería de oro artesanal y de pequeña escala (MAPE). Debido a su distribución global y su sensibilidad a la contaminación, las aves brindan una oportunidad valiosa como bioindicadores para evaluar cómo las emisiones de Hg afectan la capacidad de un ecosistema para sustentar la biodiversidad y, en última instancia, la salud global. Presentamos la más grande base de datos sobre concentraciones de Hg en aves Neotropicales (n = 2,316) para establecer una línea base para los niveles de exposición a Hg en 322 especies de aves de nueve países de América Central, América del Sur, y el Caribe. Encontramos patrones de las concentraciones de Hg en aves de los trópicos que se asemejan a los de las regiones templadas: mostrando una bioacumulación consistente a través de grupos funcionales y una alta variación espaciotemporal. Las especies de aves que ocupan posiciones más altas en la cadena trófica y en hábitats acuáticos registraron concentraciones elevadas de Hg que podrían tener efectos negativos en su éxito reproductivo. Es importante resaltar que las concentraciones de Hg en las aves de los sitios afectados por la MAPE fueron cuatro veces más altas que las de los sitios control y además difirió por temporada para ciertos nichos tróficos. Desarrollamos esta síntesis a través de una red de investigación colaborativa, la Iniciativa de Investigación Tropical para la Conservación y Ecotoxicología Aviar (TRACE), que ejemplifica un intercambio de datos inclusivo, equitativo e internacional. Si bien nuestros hallazgos sugieren una necesidad urgente de evaluar los sesgos en el muestreo, los mecanismos, y las consecuencias de la exposición al Hg en las comunidades de aves tropicales, la Iniciativa TRACE proporciona un marco para abordar estos objetivos. Nuestro esfuerzo colectivo tiene como propósito respaldar y brindar información a las entidades locales, científicas, y gubernamentales, incluyendo las Partes de la Convención de Minamata de las Naciones Unidas sobre el Mercurio, mientras continuamos trabajando juntos para comprender cómo la contaminación por Hg en los trópicos puede afectar la salud pública, el funcionamiento de los ecosistemas, y la conservación de la biodiversidad. Total mercury (THg) concentrations (µg/g) and sample sizes of birds across Central America, South America, and the West Indies from 2007­2023. Point size and color are arranged in order of increasing THg concentration and hexagonal grid cells are colored in terms of increasing sample size.

Factors influencing mercury exposure in Arctic-breeding shorebirds.

Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013. Blood Hg concentrations, which reflect Hg exposure in the local area in individual shorebirds: 1) ranged from 0.01-3.52 µg/g ww, with an overall mean of 0.30 ± 0.27 µg/g ww; 2) were influenced by species and study site, but not sampling year, with birds sampled near Utqiagvik, AK, having the highest concentrations; and 3) were influenced by foraging habitat at some sites. Feather Hg concentrations, which reflected Hg exposure from the wintering grounds: 1) ranged from 0.07-12.14 µg/g fw in individuals, with an overall mean of 1.14 ± 1.18 µg/g fw; and 2) were influenced by species and year. Most Arctic-breeding shorebirds had blood and feather Hg concentrations at levels where no adverse effects of exposure were predicted, though some individuals sampled near Utqiagvik had Hg levels that would be considered of concern. Overall, these data increase our understanding of how Hg is distributed in the various shorebird breeding areas of the Arctic, what factors predispose Arctic-breeding shorebirds to Hg exposure, and lay the foundation for future monitoring efforts.

Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells.

Inhibitors of the lipogenic enzyme fatty acid synthase (FASN) have attracted much attention in the last decade as potential targeted cancer therapies. However, little is known about the molecular determinants of cancer cell sensitivity to FASN inhibitors (FASNis), which is a major roadblock to their therapeutic application. Here, we find that pharmacological starvation of endogenously produced FAs is a previously unrecognized metabolic stress that heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors. Evaluation of the death decision circuits controlled by the BCL-2 family of proteins revealed that FASN inhibition is accompanied by the upregulation of the pro-death BH3-only proteins BIM, PUMA, and NOXA. Cell death triggered by FASN inhibition, which causally involves a palmitate/NADPH-related redox imbalance, is markedly diminished by concurrent loss of BIM or PUMA, suggesting that FASN activity controls cancer cell survival by fine-tuning the BH3 only proteins-dependent mitochondrial threshold for apoptosis. FASN inhibition results in a heightened mitochondrial apoptosis priming, shifting cells toward a primed-for-death state "addicted" to the anti-apoptotic protein BCL-2. Accordingly, co-administration of a FASNi synergistically augments the apoptosis-inducing activity of the dual BCL-XL/BCL-2 inhibitor ABT-263 (navitoclax) and the BCL-2 specific BH3-mimetic ABT-199 (venetoclax). FASN inhibition, however, fails to sensitize breast cancer cells to MCL-1- and BCL-XL-selective inhibitors such as S63845 and A1331852. A human breast cancer xenograft model evidenced that oral administration of the only clinically available FASNi drastically sensitizes FASN-addicted breast tumors to ineffective single-agents navitoclax and venetoclax in vivo. In summary, a novel FASN-driven facet of the mitochondrial priming mechanistically links the redox-buffering mechanism of FASN activity to the intrinsic apoptotic threshold in breast cancer cells. Combining next-generation FASNis with BCL-2-specific BH3 mimetics that directly activate the apoptotic machinery might generate more potent and longer-lasting antitumor responses in a clinical setting.

Splice Junction Identification using Long Short-Term Memory Neural Networks.

Background: Splice junctions are the key to move from pre-messenger RNA to mature messenger RNA in many multi-exon genes due to alternative splicing. Since the percentage of multi-exon genes that undergo alternative splicing is very high, identifying splice junctions is an attractive research topic with important implications. Objective: The aim of this paper is to develop a deep learning model capable of identifying splice junctions in RNA sequences using 13,666 unique sequences of primate RNA. Methods: A Long Short-Term Memory (LSTM) Neural Network model is developed that classifies a given sequence as EI (Exon-Intron splice), IE (Intron-Exon splice), or N (No splice). The model is trained with groups of trinucleotides and its performance is tested using validation and test data to prevent bias. Results: Model performance was measured using accuracy and f-score in test data. The finalized model achieved an average accuracy of 91.34% with an average f-score of 91.36% over 50 runs. Conclusion: Comparisons show a highly competitive model to recent Convolutional Neural Network structures. The proposed LSTM model achieves the highest accuracy and f-score among published alternative LSTM structures.

A green wave of saltmarsh productivity predicts the timing of the annual cycle in a long-distance migratory shorebird.

Understanding how migratory animals respond to spatial and temporal variation in habitat phenology is critical for identifying selection pressures and tradeoffs at different life history stages. We examined the influence of breeding habitat phenology on life history timing of the eastern willet (Tringa semipalmata semipalmata) across a latitudinal gradient of breeding sites on the east coast of North America. To describe migration and life history timing, we deployed light-level geolocators on willets at breeding sites in New Jersey, Massachusetts and Maine, USA and evaluated additional data on life history timing and migratory connectivity from previous studies, eBird and band recoveries. Willets from Nova Scotia to Georgia winter exclusively on the Atlantic coast of northern South America and share common stopover sites. The timing of wintering site departure, breeding site arrival, nesting and southbound departure was later for birds breeding at higher latitudes while the duration of all life phases was similar across sites. Regardless of latitude, nesting corresponded with a consistent stage of seasonal salt marsh biomass accumulation and with peak spring temperature acceleration (GDD jerk). Temperature acceleration and salt marsh biomass were closely correlated with each other across the 11° latitudinal gradient we examined and with the timing of nest initiation across the northern 6° of this gradient. For this northern 6° of latitude, these results suggest that the timing of migration and breeding events in the annual cycle of eastern willets is constrained by a phenological "green wave" of spring salt marsh productivity at breeding sites.

Shallow Distance Dependence for Proton-Coupled Tyrosine Oxidation in Oligoproline Peptides.

We have explored the kinetic effect of increasing electron transfer (ET) distance in a biomimetic, proton-coupled electron-transfer (PCET) system. Biological ET often occurs simultaneously with proton transfer (PT) in order to avoid the high-energy, charged intermediates resulting from the stepwise transfer of protons and electrons. These concerted proton-electron-transfer (CPET) reactions are implicated in numerous biological ET pathways. In many cases, PT is coupled to long-range ET. While many studies have shown that the rate of ET is sensitive to the distance between the electron donor and acceptor, extensions to biological CPET reactions are sparse. The possibility of a unique ET distance dependence for CPET reactions deserves further exploration, as this could have implications for how we understand biological ET. We therefore explored the ET distance dependence for the CPET oxidation of tyrosine in a model system. We prepared a series of metallopeptides with a tyrosine separated from a Ru(bpy)32+ complex by an oligoproline bridge of increasing length. Rate constants for intramolecular tyrosine oxidation were measured using the flash-quench transient absorption technique in aqueous solutions. The rate constants for tyrosine oxidation decreased by 125-fold with three added proline residues between tyrosine and the oxidant. By comparison, related intramolecular ET rate constants in very similar constructs were reported to decrease by 4-5 orders of magnitude over the same number of prolines. The observed shallow distance dependence for tyrosine oxidation is proposed to originate in part from the requirement for stronger oxidants, leading to a smaller hole-transfer effective tunneling barrier height. The shallow distance dependence observed here and extensions to distance-dependent CPET reactions have potential implications for long-range charge transfers.

Long-term monitoring of mercury in adult saltmarsh sparrows breeding in Maine, Massachusetts and New York, USA 2000-2017.

Here we report on the results of a long-term study of mercury exposure in a songbird species, the saltmarsh sparrow (Ammodramus caudacutus). We measured total mercury concentrations in blood (n = 840) and feathers (n = 560) of adult saltmarsh sparrows at six locations between 2000 and 2017: Rachel Carson National Wildlife Refuge (RCNWR) in Wells, Maine; Scarborough Marsh State Wildlife Management Area in Scarborough, Maine; Parker River National Wildlife Refuge on Plum Island, Massachusetts; Pine Neck Preserve in Southampton, Long Island, New York; and North Cinder and North Green Sedge Islands off the coast of Long Island, New York. During the 12-17 year sampling periods, we found that mercury exposure differed by site and year but there was no consistent temporal trend across sites. Blood mercury concentrations declined only at RCNWR in Maine. We also found seasonal variation in blood mercury concentrations and a positive relationship between mercury concentrations of blood and innermost primary feather, but not between blood and tail feather.

Spatial Auto-Regressive Analysis of Correlation in 3-D PET With Application to Model-Based Simulation of Data.

When a scanner is installed and begins to be used operationally, its actual performance may deviate somewhat from the predictions made at the design stage. Thus it is recommended that routine quality assurance (QA) measurements be used to provide an operational understanding of scanning properties. While QA data are primarily used to evaluate sensitivity and bias patterns, there is a possibility to also make use of such data sets for a more refined understanding of the 3-D scanning properties. Building on some recent work on analysis of the distributional characteristics of iteratively reconstructed PET data, we construct an auto-regression model for analysis of the 3-D spatial auto-covariance structure of iteratively reconstructed data, after normalization. Appropriate likelihood-based statistical techniques for estimation of the auto-regression model coefficients are described. The fitted model leads to a simple process for approximate simulation of scanner performance-one that is readily implemented in an R script. The analysis provides a practical mechanism for evaluating the operational error characteristics of iteratively reconstructed PET images. Simulation studies are used for validation. The approach is illustrated on QA data from an operational clinical scanner and numerical phantom data. We also demonstrate the potential for use of these techniques, as a form of model-based bootstrapping, to provide assessments of measurement uncertainties in variables derived from clinical FDG-PET scans. This is illustrated using data from a clinical scan in a lung cancer patient, after a 3-minute acquisition has been re-binned into three consecutive 1-minute time-frames. An uncertainty measure for the tumor SUVmax value is obtained. The methodology is seen to be practical and could be a useful support for quantitative decision making based on PET data.

Higher Prevalence of Babesia microti than Borrelia burgdorferi in Small Mammal Species in Central Pennsylvania, United States.

Babesia microti can lead to severe babesiosis in immunosuppressed populations, but due to high numbers of asymptomatic cases, clinical reporting is unable to define its geographic distribution. Although Lyme disease caused by Borrelia burgdorferi is endemic throughout Pennsylvania (PA), human babesiosis is under recognized, despite sharing the same vector and primary reservoir host. Ixodes ticks are known to carry B. microti throughout PA, but information about pathogen prevalence in small mammal reservoirs remains limited. Characterizing B. microti prevalence in these small mammals can elucidate mechanisms of pathogen spread and define geographic areas where humans are at risk of infection. We tested 692 small mammals across eight contiguous counties in central PA for molecular evidence of B. microti and B. burgdorferi. In total, six different small mammal species were collected. The overall prevalence of B. microti was 32% with similar rates observed across all counties. Surprisingly, this was higher than the prevalence of B. burgdorferi at 21%. In fact, high rates of B. microti were found in all six species, and both pathogens were identified in 11% of mammals tested. The prevalence of B. microti was highest in Myodes gapperi (southern red-backed vole) at 39% despite Peromyscus leucopus (white-footed mouse) being considered the primary reservoir host for B. microti. In conclusion, B. microti has a high prevalence across multiple small mammal species throughout central PA. This prevalence is greater than B. burgdorferi despite a much higher incidence of Lyme disease compared to babesiosis in PA. Although it remains unknown how the prevalence of B. microti in small mammal hosts corresponds to human infection rates, the high pathogen prevalence of B. microti suggests that it is an emerging pathogen in this area. Currently, babesiosis is not a reportable disease in PA, and additional studies are warranted to evaluate its clinical significance in this geographic region.

The effects of climate, habitat, and trophic position on methylmercury bioavailability for breeding New York songbirds.

Mercury (Hg) is a global pollutant that affects songbird populations across a variety of ecosystems following conversion to methylmercury (MeHg)-a form of Hg with high potential for bioaccumulation and bioavailability. The amount of bioavailable MeHg in an ecosystem is a function of the amount of total Hg present as well as Hg methylation rates, which vary across the landscape in space and time, and trophic transfer. Using songbirds as an indicator of MeHg bioavailability in terrestrial ecosystems, we evaluated the role of habitat, climate, and trophic level in dictating MeHg exposure risk across a variety of ecosystems. To achieve this objective, 2243 blood Hg samples were collected from 81 passerine and near-passerine species in New York State, USA, spanning 10 different sampling regions from Long Island to western New York. Using a general linear mixed modeling framework that accounted for regional variation in sampling species composition, we found that wetland habitat area within 100 m of capture location, 50-year average of summer maximum temperatures, and trophic position inferred using stable isotope analysis were all correlated with songbird blood Hg concentrations statewide. Moreover, these patterns had a large degree of spatial variability suggesting that the drivers of MeHg bioavailability differed significantly across the state. Mercury deposition, land cover, and climate are all expected to change throughout the northeastern United States in the coming decades. Terrestrial MeHg bioavailability will likely respond to these changes. Focused research and monitoring efforts will be critical to understand how exposure risk responds to global environmental change across the landscape.

Development of body knowledge as measured by arm differentiation in infants: From global to local?

The ability to sense and use the body parts in an organized and differentiated manner is a precursor of body knowledge in infancy. To acquire this ability, the infant's brain might explore the perceptual consequences of its bodily actions. Undifferentiated body movements would gradually be replaced by more precise actions. Only a very few studies have tested this 'global-to-local' hypothesis, and none of them have so far been replicated. In this study, we assessed arm differentiation in 4-, 6-, and 8-month-old infants using a new contingency detection task in which infants have to detect a contingency between one of their arms' activity and an audiovisual stimulus on a screen. We found that 4- to 8-month-old infants seem to be able to use their arms in a differentiated manner. However, surprisingly, we were not able to show a developmental trend in arm differentiation between 4 and 8 months of age. Statement of contribution What is already known on this subject? Foetuses and infants possess coarse control of their body and may be sensitive to sensory feedback caused by their own movements. Body knowledge might develop during the first year of life in what can be called a 'global-to-local' manner. Nevertheless, the precise age at which infants come to possess well-differentiated local body knowledge requires further investigation. What the present study adds? 4- to 8-month-old infants seem able to use their arms in a differentiated manner when exposed to an audiovisual stimulation contingent on movements of one of their arms. However, we found no developmental trend in arm differentiation between 4 and 8 months of age. We hypothesize that infants' sensitivity to sensorimotor contingencies and their ability to narrow down contingencies to a specific limb might evolve with age as a function of the infant's current sensorimotor interests.

A global-scale assessment of fish mercury concentrations and the identification of biological hotspots.

We present data on a rapid assessment of fish Hg concentrations from 40 different waterbodies in 26 countries that includes data on 451 fish of 92 species. Significant differences in fish Hg concentrations were observed across fish foraging guilds and in general, higher trophic level fish (i.e., piscivores and carnivores) showed the highest mean total Hg (THg) concentrations. However, elevated THg concentrations observed in a lower trophic level, detrivorous species highlights the importance of understanding Hg concentrations across a wide range of trophic levels, and also characterizing site-specific processes that influence methylmercury (MeHg) bioavailability. A linear mixed effects model was used to evaluate the effects of length, trophic level, sampling location, and taxonomy on THg concentrations. A positive, significant relationship between THg in fish and fish size, trophic level, and latitude of the sampling site was observed. A comparison of Hg concentrations across all sites identifies biological mercury hotspots, as well as sites with reduced Hg concentrations relative to our overall sampling population mean Hg concentration. Results from this study highlight the value of rapid assessments on the availability of methylmercury in the environment using fish as bioindicators and the need for expanded biomonitoring efforts in understudied regions of the world. This study also provides insights for the future design and implementation of large-scale Hg biomonitoring efforts intended to evaluate the effectiveness of future Hg reduction strategies instituted by the Minamata Convention on Mercury.

Immune-Mediated Control of a Dormant Neurotropic RNA Virus Infection.

Genomic material from many neurotropic RNA viruses (e.g., measles virus [MV], West Nile virus [WNV], Sindbis virus [SV], rabies virus [RV], and influenza A virus [IAV]) remains detectable in the mouse brain parenchyma long after resolution of the acute infection. The presence of these RNAs in the absence of overt central nervous system (CNS) disease has led to the suggestion that they are viral remnants, with little or no potential to reactivate. Here we show that MV RNA remains detectable in permissive mouse neurons long after challenge with MV and, moreover, that immunosuppression can cause RNA and protein synthesis to rebound, triggering neuropathogenesis months after acute viral control. Robust recrudescence of viral transcription and protein synthesis occurs after experimental depletion of cells of the adaptive immune response and is associated with a loss of T resident memory (Trm) lymphocytes within the brain. The disease associated with loss of immune control is distinct from that seen during the acute infection: immune cell-depleted, long-term-infected mice display severe gait and motor problems, in contrast to the wasting and lethal disease that occur during acute infection of immunodeficient hosts. These results illuminate the potential consequences of noncytolytic, immune-mediated viral control in the CNS and demonstrate that what were once considered "resolved" RNA viral infections may, in fact, induce diseases later in life that are distinct from those caused by acute infection.IMPORTANCE Viral infections of neurons are often not cytopathic; thus, once-infected neurons survive, and viral RNAs can be detected long after apparent viral control. These RNAs are generally considered viral fossils, unlikely to contribute to central nervous system (CNS) disease. Using a mouse model of measles virus (MV) neuronal infection, we show that MV RNA is maintained in the CNS of infected mice long after acute control and in the absence of overt disease. Viral replication is suppressed by the adaptive immune response; when these immune cells are depleted, viral protein synthesis recurs, inducing a CNS disease that is distinct from that observed during acute infection. The studies presented here provide the basis for understanding how persistent RNA infections in the CNS are controlled by the host immune response, as well as the pathogenic consequences of noncytolytic viral control.

Combining structural and textural assessments of volumetric FDG-PET uptake in NSCLC.

Numerous studies have reported the prognostic utility of texture analyses and the effectiveness of radiomics in PET and PET/CT assessment of non-small cell lung cancer (NSCLC). Here we explore the potential, relative to this methodology, of an alternative model-based approach to tumour characterization, which was successfully applied to sarcoma in previous works. The spatial distribution of 3D FDG-PET uptake is evaluated in the spatial referential determined by the best-fitting ellipsoidal pattern, which provides a univariate uptake profile function of the radial position of intratumoral voxels. A group of structural features is extracted from this fit that include two heterogeneity variables and statistical summaries of local metabolic gradients. We demonstrate that these variables capture aspects of tumour metabolism that are separate to those described by conventional texture features. Prognostic model selection is performed in terms of a number of classifiers, including stepwise selection of logistic models, LASSO, random forests and neural networks with respect to two-year survival status. Our results for a cohort of 93 NSCLC patients show that structural variables have significant prognostic potential, and that they may be used in conjunction with texture features in a traditional radiomics sense, towards improved baseline multivariate models of patient overall survival. The statistical significance of these models also demonstrates the relevance of these machine learning classifiers for prognostic variable selection.

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone.

BACKGROUND: Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required. OBJECTIVES: The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy. METHODS: Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis. RESULTS: All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm2 vs. post-treatment 0.08/mm2, p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D. CONCLUSIONS: TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

Know Your Body Through Intrinsic Goals.

The first "object" that newborn children play with is their own body. This activity allows them to autonomously form a sensorimotor map of their own body and a repertoire of actions supporting future cognitive and motor development. Here we propose the theoretical hypothesis, operationalized as a computational model, that this acquisition of body knowledge is not guided by random motor-babbling, but rather by autonomously generated goals formed on the basis of intrinsic motivations. Motor exploration leads the agent to discover and form representations of the possible sensory events it can cause with its own actions. When the agent realizes the possibility of improving the competence to re-activate those representations, it is intrinsically motivated to select and pursue them as goals. The model is based on four components: (1) a self-organizing neural network, modulated by competence-based intrinsic motivations, that acquires abstract representations of experienced sensory (touch) changes; (2) a selector that selects the goal to pursue, and the motor resources to train to pursue it, on the basis of competence improvement; (3) an echo-state neural network that controls and learns, through goal-accomplishment and competence, the agent's motor skills; (4) a predictor of the accomplishment of the selected goals generating the competence-based intrinsic motivation signals. The model is tested as the controller of a simulated simple planar robot composed of a torso and two kinematic 3-DoF 2D arms. The robot explores its body covered by touch sensors by moving its arms. The results, which might be used to guide future empirical experiments, show how the system converges to goals and motor skills allowing it to touch the different parts of own body and how the morphology of the body affects the formed goals. The convergence is strongly dependent on competence-based intrinsic motivations affecting not only skill learning and the selection of formed goals, but also the formation of the goal representations themselves.

Fetal Origin of Sensorimotor Behavior.

The aim of this article is to track the fetal origin of infants' sensorimotor behavior. We consider development as the self-organizing emergence of complex forms from spontaneously generated activity, governed by the innate capacity to detect and memorize the consequences of spontaneous activity (contingencies), and constrained by the sensory and motor maturation of the body. In support of this view, we show how observations on fetuses and also several fetal experiments suggest that the fetus's first motor activity allows it to feel the space around it and to feel its body and the consequences of its movements on its body. This primitive motor babbling gives way progressively to sensorimotor behavior which already possesses most of the characteristics of infants' later behavior: repetition of actions leading to sensations, intentionality, some motor control and oriented reactions to sensory stimulation. In this way the fetus can start developing a body map and acquiring knowledge of its limited physical and social environment.

Changes in mercury exposure of marine birds breeding in the Gulf of Maine, 2008-2013.

Mercury is a potent contaminant that can disrupt an organism's behavior and physiology, ultimately affecting reproductive success. Over the last 100 years, environmental deposition of anthropogenic sourced mercury has increased globally, particularly in the U.S. Northeast region. Marine birds are considered effective bioindicators of ecosystem health, including persistent marine contaminants. Goodale et al. (2008) found that mercury exposure exceeded adverse effects levels in some marine bird species breeding across the Gulf of Maine. We re-examined mercury contamination in four species identified as effective bioindicators. Compared with the previous sampling effort, inshore-feeding species showed significant increases in mercury exposure, while one pelagic-feeding species remained stable. This suggests that a major shift may have occurred in methylmercury availability in inshore waters of the Gulf of Maine. Understanding environmental mercury trends in the Gulf of Maine, and its significance to marine birds and other taxa will require a dedicated, standardized, long-term monitoring scheme.

Exploring the solid state phase transition in dl-norvaline with terahertz spectroscopy.

dl-Norvaline is a molecular crystal at room temperature and it undergoes a phase transition when cooled below 190 K. This phase transition is believed to be Martensitic, thus making it of particular interest for molecular machines. In this paper we investigate this phase transition by measuring its terahertz (THz) spectrum over a range of temperatures. Temperature-dependent THz time-domain spectroscopy (THz-TDS) measurements reveal that the transition temperature (Tß→α) is 190 K. The influence of nucleation seeds was analyzed by determining the Tß→α of molecular crystals with varying grain size. Grains of 5 µm or less result in a lower transition temperature (Tß→α = 180 K) compared to larger grains of 125-250 µm (Tß→α = 190 K). Additionally, we gain insight into the physical process of the phase transition via temperature-dependent THz-TDS spectra of doped and mixed molecular crystals. The addition of molecular dopants, which differ from dl-norvaline only at the end of the side chain which resides in the hydrophobic layers of the crystal, decreases Tß→α. This is consistent with a solid-solid phase transition in which the unit cell shifts along this hydrophobic layer, and it leads us to believe that the phase transition in dl-norvaline is Martensitic in nature.

Optimization of Photoanodes for Photocatalytic Water Oxidation by Combining a Heterogenized Iridium Water-Oxidation Catalyst with a High-Potential Porphyrin Photosensitizer.

The development of water-splitting dye-sensitized photoelectrochemical cells has gained interest owing to their ability to generate renewable fuels from solar energy. In this study, photoanodes were assembled from a SnO2 film sensitized with a combination of a high-potential CF3 -substituted porphyrin dye with a tetrahydropyranyl-protected hydroxamic acid surface-anchoring group and a Cp*Ir (Cp*=pentamethylcyclopentadienyl) water-oxidation catalyst containing a silatrane anchoring group. The dye/catalyst ratios were varied from 2:1 to 32:1 to optimize the photocatalytic water oxidation. Photoelectrochemical measurements showed not only more stable and reproducible photocurrents for lower dye/catalyst ratios but also improved photostability. O2 production was confirmed in real time over a 20 h period with a Clark electrode. Photoanodes prepared from 2:1 and 8:1 dye/catalyst sensitization solutions provided the most active electrodes for photocatalytic water oxidation and performed approximately 30-35 turnovers in 20 h.