Adipokines secreted from white adipose tissue play a role in metabolic crosstalk and homeostasis, whereas the brown adipose secretome is less explored. We performed high-sensitivity ...mass-spectrometry-based proteomics on the cell media of human adipocytes derived from the supraclavicular brown adipose and from the subcutaneous white adipose depots of adult humans. We identified 471 potentially secreted proteins covering interesting categories such as hormones, growth factors, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated between brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, and among these was ependymin-related protein 1 (EPDR1). EPDR1 was detected in human plasma, and functional studies suggested a role for EPDR1 in thermogenic determination during adipogenesis. In conclusion, we report substantial differences between the secretomes of brown and white human adipocytes and identify novel candidate batokines that can be important regulators of human metabolism.
Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the ...direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.
The geometry of the accretion flow around stellar-mass black holes can change on timescales of days to months1–3. When a black hole emerges from quiescence (that is, it ‘turns on’ after accreting ...material from its companion) it has a very hard (high-energy) X-ray spectrum produced by a hot corona4,5 positioned above its accretion disk, and then transitions to a soft (lower-energy) spectrum dominated by emission from the geometrically thin accretion disk, which extends to the innermost stable circular orbit6,7. Much debate persists over how this transition occurs and whether it is driven largely by a reduction in the truncation radius of the disk8,9 or by a reduction in the spatial extent of the corona10,11. Observations of X-ray reverberation lags in supermassive black-hole systems12,13 suggest that the corona is compact and that the disk extends nearly to the central black hole14,15. Observations of stellar-mass black holes, however, reveal equivalent (mass-scaled) reverberation lags that are much larger16, leading to the suggestion that the accretion disk in the hard-X-ray state of stellar-mass black holes is truncated at a few hundreds of gravitational radii from the black hole17,18. Here we report X-ray observations of the black-hole transient MAXI J1820+07019,20. We find that the reverberation time lags between the continuum-emitting corona and the irradiated accretion disk are 6 to 20 times shorter than previously seen. The timescale of the reverberation lags shortens by an order of magnitude over a period of weeks, whereas the shape of the broadened iron K emission line remains remarkably constant. This suggests a reduction in the spatial extent of the corona, rather than a change in the inner edge of the accretion disk.
Osteoarthritis (OA) has recently been suggested to be associated with diabetes. However, this association often disappears when accounting for body mass index (BMI), suggesting that mechanical stress ...may be a confounding factor. We investigated the combined influence of glucose level and loading stress on OA progression using a novel whole joint-in-motion (JM) culture system.
Whole mouse knee joints were placed in an enclosed chamber with culture media and actuated to recapitulate leg movement, with a dynamic stress regimen of 0.5 Hz, 8 h/day for 7 days. These joints were treated with varying levels of glucose and controlled for osmolarity and diffusion. Joint movement and joint space were examined by X-ray fluoroscopy and microCT. Cartilage matrix levels were quantified by blinded Mankin scoring and immunohistochemistry.
Culturing in the JM device facilitated proper leg extension and flexion movements, and adequate mass transport for analyzing the effect of glucose on cartilage. Treatment with higher levels of glucose either via media supplementation or intra-articular injection caused a significant decrease in levels of glycosaminoglycan (GAG) and an increase in aggrecan neoepitope in articular cartilage, but only under dynamic stress. Additionally, collagen II level was slightly reduced by high glucose levels.
High levels of glucose and dynamic stress have permissive effects on articular cartilage GAG loss and aggrecan degradation, implicating that mechanical stress confounds the association of diabetes with OA. The JM device supports novel investigation of mechanical stress on the integrity of an intact living mouse joint to provide insights into OA pathogenesis.
Different configurations of plasmonically active metal nanoparticles in TiO2 composites significantly affect the photocatalytic performance (up to×100 times).
•Designed composites with up to 2 orders ...higher activity than bare TiO2.•Effects of plasmonic excitations in photocatalysis scrutinized.•Catalytic activity evaluated under separate plasmonic and bandgap excitation.•Spectroscopically proved interfacial charge transfer from TiO2 to nanoparticles.•Experimentally confirm plasmonic near- and far-field effects in photocatalysis.
Model nanocomposite photocatalysts consisting of undoped TiO2 films with optically active Ag or Au nanoparticles (NPs) were designed, fabricated, and examined to address the role of plasmon excitations in their performance. Different composition configurations were tested in which the NPs were either facing the reaction environment or not, and in direct contact or not with TiO2. We found, as measured for the reactions of methanol and ethylene oxidation in two different photoreactors, that composites always show enhanced activity (up to ×100 for some configurations) compared to bare TiO2. We deduced from in situ localized surface plasmon resonance spectroscopy measurements that the interfacial charge transfer from TiO2 to NPs plays a major role in the activity enhancement for composite configurations where particles are in direct contact with TiO2. Plasmonic near- and far-field effects were only observed when the plasmon resonance energy overlaps with the bandgap energy of undoped TiO2.
The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant ...size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
•Residual anxiety in bipolar disorder impedes treatment effect and prognosis•10 trials investigated treatments targeting anxiety in remitted bipolar disorder•There is limited evidence for efficacy of ...treatments targeting anxiety•Common methodological challenges impede the success of treatment trials•These challenges must be addressed to aid the success of future trials
Anxiety symptoms are prevalent in bipolar disorder (BD) even during periods of remission and impede treatment efficacy, prognosis and functional capacity. This highlights a pressing clinical need to identify novel effective anxiety treatments. This systematic review aimed to evaluate the evidence within the field.
Following PRISMA guidelines, we conducted a systematic search on PubMed, PsycInfo, EMBASE and Cochrane Library for randomised controlled trials (RCTs) targeting anxiety in remitted BD patients.
We identified 10 RCTs investigating the effects of psychological or pharmacological treatments on anxiety in remitted BD patients. Two studies of transdiagnostic personalised cognitive behavioural therapy (CBT) found a treatment-related reduction in anxiety. This evidence was preliminary given small sample size and use of self-report measures in a single-blind trial design, respectively. The remaining six psychological intervention trials provided more preliminary evidence due to several methodological challenges. The two pharmacological studies found anxiolytic effects of add-on olanzapine or methylene blue to lithium treatment, respectively. Nevertheless, this evidence should be interpreted with caution given high drop-out rates and substantial side-effects that may have impeded blinding.
We did not conduct a quantitative meta-analysis.
There is preliminary evidence for beneficial effects of modified CBT and add-on pharmacotherapy on residual anxiety in BD. Future trials should pre-screen participants for anxiety, define one clinician-rated anxiety measurement as a primary outcome, and employ intention-to-treat analysis to assess treatment effect. This will advance treatment development and enable personalised approaches to address residual anxiety in BD, which has great clinical relevance.
Summary
Antimicrobial (AM) resistance is an increasing problem in human and veterinary medicine. To manage this problem, the usage of AM should be reduced in pig farming, as well as in other areas. ...It is important to investigate the factors that influence both pig farmers' and veterinarians' intentions to reduce AM usage, which is a prerequisite for developing intervention measures. We conducted a mail survey among pig farmers (N = 1,294) and an online survey among veterinarians (N = 334) in Belgium, Denmark, France, Germany, Sweden and Switzerland. The farmers' survey assessed the perceived risks and benefits of and need for AM usage; the intention to reduce AM usage; farmers' efficacy (i.e. perception of their ability to reduce AM usage); support from their veterinarian; and the future reduction potential of AM usage. Additionally, self‐reported reduction behaviours, the perceived farmers' barriers to reduce AM usage and relationships with farmers were assessed in the veterinarians' survey. The results showed that farmers and veterinarians had similar perceptions of the risks and benefits of AM usage. Veterinarians appeared to be more optimistic than pig farmers about reducing AM usage in pig farming. Farmers believed that their efficacy over AM reduction was relatively high. Farmers' intention to reduce AM usage and veterinarians' self‐reported reduction behaviours were mainly associated with factors concerning the feasibility of reducing AM usage. To promote prudent AM usage, pig farmers should learn and experience how to reduce usage by applying alternative measures, whereas veterinarians should strengthen their advisory role and competencies to support and educate farmers.
Arctic plant communities are altered by climate changes. The magnitude of these alterations depends on whether species distributions are determined by macroclimatic conditions, by factors related to ...local topography, or by biotic interactions. Our current understanding of the relative importance of these conditions is limited due to the scarcity of studies, especially in the High Arctic. We investigated variations in vascular plant community composition and species richness based on 288 plots distributed on three sites along a coast‐inland gradient in Northeast Greenland using a stratified random design. We used an information theoretic approach to determine whether variations in species richness were best explained by macroclimate, by factors related to local topography (including soil water) or by plant‐plant interactions. Latent variable models were used to explain patterns in plant community composition. Species richness was mainly determined by variations in soil water content, which explained 35% of the variation, and to a minor degree by other variables related to topography. Species richness was not directly related to macroclimate. Latent variable models showed that 23.0% of the variation in community composition was explained by variables related to topography, while distance to the inland ice explained an additional 6.4 %. This indicates that some species are associated with environmental conditions found in only some parts of the coast–inland gradient. Inclusion of macroclimatic variation increased the model's explanatory power by 4.2%. Our results suggest that the main impact of climate changes in the High Arctic will be mediated by their influence on local soil water conditions. Increasing temperatures are likely to cause higher evaporation rates and alter the distribution of late‐melting snow patches. This will have little impact on landscape‐scale diversity if plants are able to redistribute locally to remain in areas with sufficient soil water.
Arctic plant communities are altered by climate changes. Our results strongly suggest that the main impact of climate changes in the High Arctic will be mediated by their influence on local soil water availability.
In view of climate considerations regarding the management of peatlands, there is a need to assess whether rewetting can mitigate greenhouse gas (GHG) emissions, and notably how site-specific ...soil-geochemistry will influence differences in emission magnitudes. However, there are inconsistent results regarding the correlation of soil properties with heterotrophic respiration (Rh) of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) from bare peat. In this study, we determined 1) soil-, and site-specific geochemical components as drivers for emissions from Rh on five Danish fens and bogs, and 2) emission magnitudes under drained and rewetted conditions. For this, a mesocosm experiment was performed under equal exposure to climatic conditions and water table depths controlled to either -40 cm, or -5 cm. For the drained soils, we found that annual cumulative emissions, accounting for all three gases, were dominated by CO2, contributing with, on average, 99 % to a varying global warming potential (GWP) of 12.2–16.9 t CO2eq ha−1 yr−1. Rewetting lowered annual cumulative emissions from Rh by 3.2–5.1 t CO2eq ha−1 yr−1 for fens and bogs, respectively, despite a high variability of site-specific CH4 emissions, contributing with 0.3–3.4 t CO2 ha−1 yr−1 to the GWP. Overall, analyses using generalized additive models (GAM) showed that emission magnitudes were well explained by geochemical variables. Under drained conditions, significant soil-specific predictor variables for CO2 flux magnitudes were pH, phosphorus (P), and the soil substrate's relative water holding capacity (WHC). When rewetted, CO2 and CH4 emissions from Rh were affected by pH, WHC, as well as contents of P, total carbon and nitrogen. In conclusion, our results found the highest GHG reduction on fen peatlands, further highlighting that peat nutrient status and acidity, and the potential availability of alternative electron acceptors, might be used as proxies for prioritising peatland areas for GHG mitigation efforts by rewetting.
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•For drained and rewetted peat, emissions were dominated by CO2.•GHG reduction highest on sites with: 1) pH 6.5, 2) rich in nutrients, iron, sulphur•Rewetting of fen peatlands was most efficient.•Biogeochemical proxies may be used for prioritising peatland areas for rewetting.
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