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Baron, J.

Publications and source records attributed to Baron, J..

10 recordsLinked to original sources

Large-scale exposure of southern seabirds to avian cholera Pasteurella multocida: scavengers as sentinels at different spatial scales

Seabird communities represent spatially structured social networks within which potential sentinels could inform us where multi-host pathogens could be present. Pasteurella multocida, the agent of avian cholera, is responsible for recurrent massive seabird mortality events on remote Amsterdam Island, Southern Indian Ocean, but little is known about its broad spatial occurrence. To explore its distribution and whether avian scavengers and predators could be used as sentinels, we screened 18 southern seabird species from 11 islands for antibodies against P. multocida (2634 plasma samples). We detected widespread but heterogeneous exposure among host populations. High seroprevalences were found in widely roaming predators and scavengers (giant petrels (Macronectes spp), and brown skua (Stercorarius antarcticus)), which could represent efficient sentinels at broad scales. Antibodies were also detected over a series of years in a non-migratory scavenger, the lesser sheathbill (Chionis minor) and an abundant penguin species, the king penguin (Aptenodytes patagonicus), suggesting that the bacterium was circulating locally at some sites. This broad scale serological screening of whole seabird host communities provides critical information to assess disease emergence risks in the context of global change.

ecology↗

Effects of Spin4 ablation in aging mice: body composition, bone density, and malignancy prevalence

Many overgrowth syndromes are associated with increased risk of tumorigenesis and malignancies. Our group recently identified a frameshift variant in histone reader SPIN4 located on the X chromosome to be a new genetic cause for human overgrowth. In the current study, we investigated the prevalence of malignancies, along with body weight, body length, body composition and bone mineral density, in Spin4 knockout mice at 18 months of age. We found that male mice lacking Spin4 have increased number of tumors and increased body length, while body weight, body composition and bone mineral density were comparable with wild-type mice. We also analyzed publicly available expression data in various types of human cancers and looked for increased or decreased expression of genes that are implicated in overgrowth syndromes and act through epigenetic mechanisms. We found that the expression of SPIN4, EZH2, and DNMT3A to be elevated in many human cancers compared to the corresponding non-malignant tissue samples. Taken together, our current findings confirm that loss of SPIN4 causes overgrowth in mice (in terms of body length) and is associated with increased prevalence in neoplasia; but does not appear to affect adiposity or bone density.

cancer biology↗

Temperature modulates PFAS accumulation and energy allocation in sheepshead minnows

Climate warming and chemical pollution shape aquatic ecosystems, yet the physiological mechanisms underlying their combined effects remain unclear. We investigated how projected increases in mean summer surface water temperature alter per- and polyfluoroalkyl substances (PFAS) toxicokinetics and their effects on sheepshead minnows (Cyprinodon variegatus) physiological performance. Adult fish were chronically exposed to an environmentally relevant PFAS mixture (perfluorooctane sulfonate (PFOS) + perfluorooctanoate (PFOA)) under current and projected mean-temperature scenarios. Tissue PFAS concentrations, whole-organism metabolic rates, swimming performance, reproductive parameters, somatic indices were assessed. Temperature modified PFAS tissue concentrations in a compound- and tissue-specific manner, promoting PFOA redistribution to eggs. Metabolic responses were temperature-dependent: at 26 {degrees}C, higher tissue PFAS concentrations were associated with elevated standard and maximum metabolic rates (SMR and MMR), maintaining aerobic scope (AS). At 28.5 {degrees}C, SMR remained stable while MMR and AS declined with rising PFAS, indicating less oxygen for energetically demanding activities. Despite unchanged swimming and reproductive outputs, an increased hepatosomatic index with increasing tissue PFAS concentrations and altered PFAS distribution suggest detoxification costs. These findings indicate that increases in mean water temperature are likely to exacerbate contaminant stress, with consequences for coastal fish population resilience and offspring development. PFAS risk assessment should consider co-stressors under projected warming. SynopsisLimited research addresses how temperature affects PFAS toxicokinetics and toxicity. This study shows that warming reshapes tissue PFAS concentrations and distribution, and influences fish energy-allocation trade-offs.

physiology↗

Pathological mutations reveal the key role of the iRhom2 N-terminus for ADAM17 binding, stability and activity.

The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.

molecular biology↗

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data

In the past decade, high-dimensional single cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation which are computationally intense and difficult to evaluate and optimize. Here we present Cyclone, an analysis pipeline integrating dimensionality reduction, clustering, evaluation and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification, but also enables the unsupervised identification of lymphocytes and mononuclear phagocytes subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on variety of cytometry datasets which will further power immunology research and provide a scaffold for biological discovery.

immunology↗

The evolution of skilled hindlimb movements in birds: A citizen science approach.

The ability to manipulate objects with limbs has evolved repeatedly among land tetrapods. Several selective forces have been proposed to explain the emergence of forelimb manipulation, however, work has been largely restricted to mammals, which prevents the testing of evolutionary hypotheses in a comprehensive evolutionary framework. In birds, forelimbs have gained the exclusive function of flight, with grasping transferred predominantly to the beak. In some birds, the feet are also used in manipulative tasks and appear to share some features with manual grasping and prehension in mammals, but this has not been systematically investigated. Here we use large online repositories of photographs and videos to quantify foot manipulative skills across a large sample of bird species (>1000 species). Our results show that a complex interaction between niche, diet and phylogeny drive the evolution of manipulative skill with the feet in birds. Furthermore, we provide strong support for the proposition that an arboreal niche is a key element in the evolution of manipulation in land vertebrates. Our systematic comparison of foot use in birds provides a solid base for understanding morphological and neural adaptations for foot use in birds, and for studying the convergent evolution of manipulative skills in birds and mammals.

animal behavior and cognition↗

On the functional role of gamma synchronization in the retinogeniculate system of the cat

AO_SCPLOWBSTRACTC_SCPLOWFast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies carried out under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multi-electrode recordings of spiking activity in the retina and the LGN of the cat, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were non-oscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent upon halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.

neuroscience↗

An olfactory pattern generator for on-demand combinatorial control of receptor activities

Olfactory systems employ combinatorial receptor codes for odors. Systematically generating stimuli that address the combinatorial possibilities of an olfactory code poses unique challenges. Here, we present a stimulus method to probe the combinatorial code, demonstrated using the Drosophila larva. This method leverages a set of primary odorants, each of which targets the activity of one olfactory receptor neuron (ORN) type at an optimal concentration. Our setup uses microfluidics to mix any combination of primary odorants on demand to activate any desired combination of ORNs. We use this olfactory pattern generator to demonstrate a spatially distributed olfactory representation in the dendrites of a single interneuron in the antennal lobe, the first olfactory neuropil of the larva. In the larval mushroom body, the next processing layer, we characterize diverse receptive fields of a population of Kenyon cells. The precision and flexibility of the olfactory pattern generator will facilitate systematic studies of processing and transformation of the olfactory code.

neuroscience↗

Invariances in a combinatorial olfactory receptor code

Animals can identify an odorant type across a wide range of concentrations, as well as detect changes in concentration for individual odorant type. How olfactory representations are structured to support these functions remains poorly understood. Here, we studied how a full complement of ORNs in the Drosophila larva encodes a broad input space of odorant types and concentrations. We find that dose-response relationships across odorants and ORN types follow the Hill function with shared cooperativity but different activation thresholds. These activation thresholds are drawn from a power law statistical distribution. A fixed activation function and power law distribution of activation thresholds underlie invariances in the encoding of odorant identity and intensity. Moreover, we find similar temporal response filters of ORNs across odorant types and concentrations. Such uniformity in the temporal filter may allow identity invariant coding in fluctuating or turbulent odor environments. Common patterns in ligand-receptor binding and sensory transduction across olfactory receptors may give rise to these observed invariances in the olfactory combinatorial code. Invariant patterns in the activity responses of individual ORNs and the ORN ensemble may simplify decoding by downstream circuits.

neuroscience↗

Linking the chemistry and reactivity of dissolved organic matter from low-latitude glaciers and rock glaciers

As glaciers thaw in response to warming, they release dissolved organic matter (DOM) to alpine lakes and streams. The United States contains an abundance of both alpine glaciers and rock glaciers. Differences in DOM composition and bioavailability between glacier types, like rock and ice glaciers, remain undefined. To assess differences in glacier and rock glacier DOM we evaluated bioavailability and molecular composition of DOM from four alpine catchments each with a glacier and a rock glacier at their headwaters. We assessed bioavailability of DOM by incubating each DOM source with a common microbial community and evaluated chemical characteristics of DOM before and after incubation using untargeted gas chromatography mass spectrometry based metabolomics (GC-MS). Prior to incubations, ice glacier and rock glacier DOM had similar C:N ratios and chemical diversity, but differences in DOM composition. Incubations with a common microbial community showed DOM from ice glacier meltwaters contained a higher proportion of bioavailable DOM (BDOM) and resulted in greater bacterial growth efficiency (BGE). After incubation, DOM composition from each source was statistically indistinguishable. This study provides an example of how MS based metabolomics can be used to assess effects of DOM composition on differences in bioavailability of DOM. Furthermore, it illustrates the importance of microbial metabolism in structuring composition of DOM. Even though rock glaciers had significantly less BDOM than ice glaciers, both glacial types still have potential to be important sources of BDOM to alpine headwaters over the coming decades.\n\nKey PointsBioavailability of organic matter released from glaciers is greater than that of rock glaciers in the Rocky Mountains.\n\nThe use of GC-MS for ecosystem metabolomics represents a novel approach for examining complex organic matter pools.\n\nBoth glaciers and rock glaciers supply highly bioavailable sources of organic matter to alpine headwaters in Colorado.

ecology↗