The global obesity epidemic demands an improved understanding of the developmental and environmental factors regulating fat storage. Adipocytes serve as major sites of fat storage and as regulators ...of energy balance and inflammation. The optical transparency of developing zebrafish provides new opportunities to investigate mechanisms governing adipocyte biology, however zebrafish adipocytes remain uncharacterized. We have developed methods for visualizing zebrafish adipocytes in vivo by labeling neutral lipid droplets with Nile Red. Our results establish that neutral lipid droplets first accumulate in visceral adipocytes during larval stages and increase in number and distribution as zebrafish grow. We show that the cellular anatomy of zebrafish adipocytes is similar to mammalian white adipocytes and identify peroxisome-proliferator activated receptor γ and fatty acid binding protein 11a as markers of the zebrafish adipocyte lineage. By monitoring adipocyte development prior to neutral lipid deposition, we find that the first visceral preadipocytes appear in association with the pancreas shortly after initiation of exogenous nutrition. Zebrafish reared in the absence of food fail to form visceral preadipocytes, indicating that exogenous nutrition is required for adipocyte development. These results reveal homologies between zebrafish and mammalian adipocytes and establish the zebrafish as a new model for adipocyte research.
The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), updates NASA’s previous satellite-era (1980 onward) reanalysis system to include additional observations and ...improvements to the Goddard Earth Observing System, version 5 (GEOS-5), Earth system model. As a major step toward a full Integrated Earth Systems Analysis (IESA), in addition to meteorological observations, MERRA-2 now includes assimilation of aerosol optical depth (AOD) from various ground-and space-based remote sensing platforms. Here, in the first of a pair of studies, the MERRA-2 aerosol assimilation is documented, including a description of the prognostic model (GEOS-5 coupled to the GOCART aerosol module), aerosol emissions, and the quality control of ingested observations. Initial validation and evaluation of the analyzed AOD fields are provided using independent observations from ground, aircraft, and shipborne instruments. The positive impact of the AOD assimilation on simulated aerosols is demonstrated by comparing MERRA-2 aerosol fields to an identical control simulation that does not include AOD assimilation. After showing the AOD evaluation, this paper takes a first look at aerosol–climate interactions by examining the shortwave, clear-sky aerosol direct radiative effect. The companion paper (Part II) evaluates and validates available MERRA-2 aerosol properties not directly impacted by the AOD assimilation (e.g., aerosol vertical distribution and absorption). Importantly, while highlighting the skill of the MERRA-2 aerosol assimilation products, both studies point out caveats that must be considered when using this new reanalysis product for future studies of aerosols and their interactions with weather and climate.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Taphonomic deformation, whether it be brittle or plastic, is possibly the most influential process hindering the correct understanding of fossil species morphology. This is especially true if the ...deformation affects type specimens or applies to or obscures taxonomically diagnostic or functionally significant traits. Target Deformation, a recently developed virtual manipulation protocol, was implemented to address this issue by applying landmark-guided restoration of the original, deformed fossils, using undeformed specimens (or parts thereof) of the same species as a reference. The enigmatic Early Pleistocene canid Canis arnensis provides a typical example of a fossil species in dire need of virtual restoration. Its lectotype specimen is heavily deformed and none of the few known skulls are well preserved, obscuring the recognition of its systematic and phylogenetic position. Our results indicate that the algorithm effectively countered the lectotype skull's laterolateral compression and its concomitant rostrocaudal elongation. Morphometrically, comparison of the retrodeformed cranium (IGF 867_W) with other specimens of the same species, and to other fossil and extant canid material, confirms IGF 867_W consistently clusters within C. arnensis variability. Overall, the evidence presented here confirms that Target Deformation provides a powerful tool to better characterize complex taxa like C. arnensis, whose knowledge is severely affected by the state of preservation of its fossil material.
Understanding how copepods may respond to ocean acidification (OA) is critical for risk assessments of ocean ecology and biogeochemistry. The perception that copepods are insensitive to OA is largely ...based on experiments with adult females. Their apparent resilience to increased carbon dioxide (pCO₂) concentrations has supported the view that copepods are ‘winners’ under OA. Here, we show that this conclusion is not robust, that sensitivity across different life stages is significantly misrepresented by studies solely using adult females. Stage‐specific responses to pCO₂ (385–6000 μatm) were studied across different life stages of a calanoid copepod, monitoring for lethal and sublethal responses. Mortality rates varied significantly across the different life stages, with nauplii showing the highest lethal effects; nauplii mortality rates increased threefold when pCO₂ concentrations reached 1000 μatm (year 2100 scenario) with LC₅₀ at 1084 μatm pCO₂. In comparison, eggs, early copepodite stages, and adult males and females were not affected lethally until pCO₂ concentrations ≥3000 μatm. Adverse effects on reproduction were found, with >35% decline in nauplii recruitment at 1000 μatm pCO₂. This suppression of reproductive scope, coupled with the decreased survival of early stage progeny at this pCO₂ concentration, has clear potential to damage population growth dynamics in this species. The disparity in responses seen across the different developmental stages emphasizes the need for a holistic life‐cycle approach to make species‐level projections to climate change. Significant misrepresentation and error propagation can develop from studies which attempt to project outcomes to future OA conditions solely based on single life history stage exposures.
With climate change, oceans are becoming increasingly nutrient limited, favouring growth of prokaryotic picoplankton at the expense of the larger protist plankton whose growth support higher trophic ...levels. Constitutive mixoplankton (CM), microalgal plankton with innate phototrophic capability coupled with phagotrophy, graze on these picoplankton, indirectly exploiting the excellent resource acquisition abilities of the prokaryotes. However, feeding rates can be very low (e.g., a few bacteria d
). For the first time, the significance of such low consumption rates has been quantified. We find that while prokaryote-carbon (C) supply to CM grown at non-limiting light was so low that it may appear insignificant (< 10%), contributions of nitrogen (N) and phosphorus (P) from ingestions of 1-12 prokaryotes d
were significant. Under limiting light, contributions of ingested C increased, also raising the contributions of N and P. The order of nutritional importance for CM growth from predation was P > N > C. Further, provision of N through internal recycling of ingested prey-N stimulates C-fixation through photosynthesis. Importantly, coupled photo-phago-mixoplanktonic activity improved CM resource affinities for both inorganic and prey-bound nutrients, enhancing the nutritional status and competitiveness of mixoplankton. With warming oceans, with increased prokaryote abundance, we expect CM to exhibit more phagotrophy.
•A new FTIR-ATR method is proposed for simultaneous measurement of microalgal biochemical content.•A univariate calibration model was built that allows comparison with conventional techniques.•High ...degrees of predictive accuracy were achieved for lipid, protein and carbohydrate.•Method benefits from small sample requirements, rapid measurement and high reproducibility.•Technique used to monitor composition of Nannochloropsis sp. culture grown to nitrogen starvation.
Analysis of bulk biochemical composition is a key in fundamental and applied studies of microalgae and is essential to understanding responses to different cultivation scenarios. Traditional biochemical methods for the quantification of lipids, carbohydrates and proteins are often time-consuming, often involve hazardous reagents, require significant amounts of biomass and are highly dependent on practitioner proficiency. This study presents a rapid and non-destructive method, utilising Fourier-Transform Infrared (FTIR) spectroscopy for the simultaneous determination of lipid, protein and carbohydrate content in microalgal biomass. A simple univariate regression was applied to sets of reference microalgal spectra of known composition and recognised IR peak integrals. A robust single-species model was constructed, with coefficients of determination r2>0.95, high predictive accuracy and relative errors below 5%. The applicability of this methodology is demonstrated by monitoring the time-resolved changes in biochemical composition of the marine alga Nannochloropsis sp. grown to nitrogen starvation.
The granuloma that forms in response to Mycobacterium tuberculosis must be carefully balanced in terms of immune responses to provide sufficient immune cell activation to inhibit the growth of the ...bacilli, yet modulate the inflammation to prevent pathology. There are likely many scenarios by which this balance can be reached, given the complexity of the immune responses induced by M. tuberculosis. In this review, we focus on the key role of the macrophage in balancing inflammation in the granuloma.
Amazonia contains one of the world's richest biotas, but origins of this diversity remain obscure. Onset of the Amazon River drainage at approximately 10.5 Ma represented a major shift in Neotropical ...ecosystems, and proto-Amazonian biotas just prior to this pivotal episode are integral to understanding origins of Amazonian biodiversity, yet vertebrate fossil evidence is extraordinarily rare. Two new species-rich bonebeds from late Middle Miocene proto-Amazonian deposits of northeastern Peru document the same hyperdiverse assemblage of seven co-occurring crocodylian species. Besides the large-bodied Purussaurus and Mourasuchus, all other crocodylians are new taxa, including a stem caiman—Gnatusuchus pebasensis—bearing a massive shovel-shaped mandible, procumbent anterior and globular posterior teeth, and a mammal-like diastema. This unusual species is an extreme exemplar of a radiation of small caimans with crushing dentitions recording peculiar feeding strategies correlated with a peak in proto-Amazonian molluscan diversity and abundance. These faunas evolved within dysoxic marshes and swamps of the long-lived Pebas Mega-Wetland System and declined with inception of the transcontinental Amazon drainage, favouring diversification of longirostrine crocodylians and more modern generalist-feeding caimans. The rise and demise of distinctive, highly productive aquatic ecosystems substantially influenced evolution of Amazonian biodiversity hotspots of crocodylians and other organisms throughout the Neogene.
After a decade of stagnation in drug development, therapeutic reversal of immune‐exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular ...carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune‐modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona‐Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications.
Background IL-25 and IL-33 belong to distinct cytokine families, but experimental mouse studies suggest their immunologic functions in type 2 immunity are almost entirely overlapping. However, only ...polymorphisms in the IL-33 pathway ( IL1RL1 and IL33 ) have been significantly associated with asthma in large-cohort genome-wide association studies. Objective We sought to identify distinct pathways for IL-25 and IL-33 in the lung that might provide insight into their roles in asthma pathogenesis and potential for therapeutic intervention. Methods IL-25 receptor–deficient (Il17rb −/− ) , IL-33 receptor–deficient (ST2, Il1rl1−/− ), and double-deficient (Il17rb −/− Il1rl1 −/− ) mice were analyzed in models of allergic asthma. Microarrays, an ex vivo lung slice airway contraction model, and Il13+/eGFP mice were then used to identify specific effects of IL-25 and IL-33 administration. Results Comparison of IL-25 and IL-33 pathway–deficient mice demonstrates that IL-33 signaling plays a more important in vivo role in airways hyperreactivity than IL-25. Furthermore, methacholine-induced airway contraction ex vivo increases after treatment with IL-33 but not IL-25. This is dependent on expression of the IL-33 receptor and type 2 cytokines. Confocal studies with Il13+/eGFP mice show that IL-33 more potently induces expansion of IL-13–producing type 2 innate lymphoid cells, correlating with airway contraction. This predominance of IL-33 activity is enforced in vivo because IL-33 is more rapidly expressed and released in comparison with IL-25. Conclusion Our data demonstrate that IL-33 plays a critical role in the rapid induction of airway contraction by stimulating the prompt expansion of IL-13–producing type 2 innate lymphoid cells, whereas IL-25–induced responses are slower and less potent.
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