Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells ...accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.
Obesity induces the formation of senescent cells, which contribute to inflammation, insulin resistance, and organ dysfunction. Senescent cell clearance may be an effective strategy for alleviating important elements of obesity‐related metabolic dysfunction.
The pachychoroid disease spectrum (PDS) includes several chorioretinal diseases that share specific choroidal abnormalities. Although their pathophysiological basis is poorly understood, diseases ...that are part of the PDS have been hypothesized to be the result of venous congestion. Within the PDS, central serous chorioretinopathy is the most common condition associated with vision loss, due to an accumulation of subretinal fluid in the macula. Central serous chorioretinopathy is characterized by distinct risk factors, most notably a high prevalence in males and exposure to corticosteroids. Interestingly, sex differences and corticosteroids are also strongly associated with specific types of arteriovenous anastomoses in the human body, including dural arteriovenous fistula and surgically created arteriovenous shunts. In this manuscript, we assess the potential of such arteriovenous anastomoses in the choroid as a causal mechanism of the PDS. We propose how this may provide a novel unifying concept on the pathophysiological basis of the PDS, and present cases in which this mechanism may play a role.
•Meta-analysis revealed multitude of factors that drive soil and water conservation.•Drivers differ between particular conservation measures and assessment methods.•Adoption of conservation measures ...revealed as emergent property of farming systems.•Urgent need to better understand dynamic socio-ecological drivers of adoption.•Methodological principles suggested to advancing science and resource conservation.
Conservation of land resources is a promising strategy for sustainable agricultural intensification in order to adapt dryland farming systems to climate, market and other stresses. At a local level, factors that drive the adoption of conservation measures operate and interact in specific ways. Linking our knowledge of the local specifications of these drivers to regional and global patterns of vulnerability can significantly enhance our understanding of land-based adaptation to global change. However, the factors that influence the adoption of conservation practices remain actively debated. Therefore, this study presents a meta-analysis of case studies that investigate the adoption of soil and water conservation measures, as an important approach to resource conservation. Synthesising 63 adoption cases in the drylands of western Africa, this meta-analysis reveals a multitude of factors that drive the adoption of soil and water conservation practices. The drivers differ strongly between particular practices and methods of analysis used in the case studies. Contributing to the broader debate on resource conservation, the findings highlight the adoption of soil and water conservation measures as an emergent property of farming systems. They demonstrate the need to better understand the socio-ecological foundation of adoption and the pathways along which adoption evolves in space and time. This study concludes with methodological principles to advance future research on the factors that drive the adoption of soil and water conservation measures as a pre-requisite of improving land-based adaptation efforts.
In the interest of mitigating global warming and climate change, the leading industrial sectors such as the iron and steel industry, as one of the most significant industrial contributors to ...anthropogenic CO2 emissions, is challenged to find more efficient and environmentally clean solutions to reduce their CO2 emissions while maintaining high process efficiencies and low production costs. To find new ways of reducing CO2 or other emissions to air, water and soil, Life Cycle Assessment (LCA) methodology can be employed to trace and quantify the most significant sources of emissions, starting from the raw-materials extraction to the final product's usage/disposal. In this work, a "cradle-to-gate" LCA study was performed, according to CML 2001 impact assessment method, for an integrated steel mill with and without carbon capture and storage (CCS). Two post-combustion CO2 capture technologies: a conventional chemical absorption technology using mono-ethanol amine (MEA) and a more innovative one based on calcium looping (CaL) are evaluated and compared against the benchmark case represented by the integrated steel mill without CCS. All results are reported on the basis of one metric ton of hot rolled coil (HRC) produced. Analysing the most significant environmental impact categories leads to the conclusion that integrating CCS into the steel production route, decreases the global warming potential in the range of 47.98–75.74%. Generally, the decrease of CO2 emissions goes along with an increase of the other impact categories regardless of the technology used, as the adoption of CCS technologies leads to efficiency losses, which, in turn, brings additional fuel demand and related other emissions. Among the investigated capture technologies, CaL shows significantly better environmental performance than the conventional amine-based CO2 capture technology as the decrease observed in eight of the environmental indicators, other than GWP, is between 2.90% and 48.87% compared to the case when MEA is applied.
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•Post-combustion CO2 capture applied to integrated steel mill.•CO2 capture using amine-based and calcium looping (CaL) technologies.•Life Cycle Assessment (LCA) applied to integrated steel mill with & without CCS.
Impaired angiogenesis has been implicated in adipose tissue dysfunction and the development of obesity and associated metabolic disorders. Here, we report the unexpected finding that vascular ...endothelial growth factor B (VEGFB) gene transduction into mice inhibits obesity-associated inflammation and improves metabolic health without changes in body weight or ectopic lipid deposition. Mechanistically, the binding of VEGFB to VEGF receptor 1 (VEGFR1, also known as Flt1) activated the VEGF/VEGFR2 pathway and increased capillary density, tissue perfusion, and insulin supply, signaling, and function in adipose tissue. Furthermore, endothelial Flt1 gene deletion enhanced the effect of VEGFB, activating the thermogenic program in subcutaneous adipose tissue, which increased the basal metabolic rate, thus preventing diet-induced obesity and related metabolic complications. In obese and insulin-resistant mice, Vegfb gene transfer, together with endothelial Flt1 gene deletion, induced weight loss and mitigated the metabolic complications, demonstrating the therapeutic potential of the VEGFB/VEGFR1 pathway.
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•VEGFB induces adipose tissue angiogenesis and improves glucose metabolism•VEGFB binding to VEGFR1 activates angiogenesis via the VEGF/VEGFR2 pathway•Increased adipose tissue perfusion improves insulin supply and function•VEGFB/VEGFR1 can promote weight loss and restore metabolic health in obese mice
Robciuc et al. show that the VEGFB/VEGFR1 pathway can be employed to engage the VEGF/VEGFR2 angiogenic pathway in adipose tissue. This mechanism increases adipose tissue vascularity without pathological side effects and provides a safe therapeutic option for restoring insulin sensitivity and promoting weight loss in obesity.
•The integration of SEWGS to iron and steel industry is investigated.•SEWGS is applied to the power section in an iron and steel plant.•SEWGS can half the CO2 emissions from the power section with ...respect to MEA.•The SPECCA of SEWGS is as low as 1.9 GJ/tCO2 which is 30 % lower than MEA.•SEWGS can reduce the cost of CO2 avoided down to 33 €/tCO2.
Mitigation of CO2 emissions in the industrial sector is one of the main climate challenges for the coming decades. This work, carried out within the STEPWISE H2020 project, performs a preliminary techno-economic assessment of the Sorption Enhanced Water Gas Shift (SEWGS) technology when integrated into the iron and steel plant to mitigate CO2 emissions. The SEWGS separates the CO2 from the iron and steel off-gases with residual energy content (i.e. Blast Furnace Gas, Basic Oxygen Furnace Gas and Coke Oven Gas) and the produced H2 is sent to the power generation section to produce the electricity required by the steel plant, while the CO2 is compressed and transported for storage. Detailed mass and energy balances are performed together with a SEWGS cost estimation to assess the energy penalty and additional costs related to CO2 capture. Results demonstrates the potential of SEWGS to capture over 80 % of CO2 in the off-gases, which results in entire plant CO2 emission reduction of 40 % with a Specific Energy Consumptions for CO2 Avoided (SPECCA) around 1.9 MJ/kgCO2. SEWGS outperforms a commercial amine scrubbing technology which has a SPECCA of 2.5 MJ/kgCO2 and only 20 % of CO2 avoided. The cost of CO2 avoided calculated on the basis of a fully integrated steel plant is around 33 €/tCO2 compared to 38 €/tCO2 of the amine technology.
Ultrafast dynamics of single molecules Brinks, Daan; Hildner, Richard; van Dijk, Erik M H P ...
Chemical Society reviews,
04/2014, Volume:
43, Issue:
8
Journal Article
Peer reviewed
Open access
The detection of individual molecules has found widespread application in molecular biology, photochemistry, polymer chemistry, quantum optics and super-resolution microscopy. Tracking of an ...individual molecule in time has allowed identifying discrete molecular photodynamic steps, action of molecular motors, protein folding, diffusion, etc. down to the picosecond level. However, methods to study the ultrafast electronic and vibrational molecular dynamics at the level of individual molecules have emerged only recently. In this review we present several examples of femtosecond single molecule spectroscopy. Starting with basic pump-probe spectroscopy in a confocal detection scheme, we move towards deterministic coherent control approaches using pulse shapers and ultra-broad band laser systems. We present the detection of both electronic and vibrational femtosecond dynamics of individual fluorophores at room temperature, showing electronic (de)coherence, vibrational wavepacket interference and quantum control. Finally, two colour phase shaping applied to photosynthetic light-harvesting complexes is presented, which allows investigation of the persistent coherence in photosynthetic complexes under physiological conditions at the level of individual complexes.
The farnesoid X receptor (FXR) is a bile acid (BA)-activated nuclear receptor that plays a major role in the regulation of BA and lipid metabolism. Recently, several studies have suggested a ...potential role of FXR in the control of hepatic carbohydrate metabolism, but its contribution to the maintenance of peripheral glucose homeostasis remains to be established. FXR-deficient mice display decreased adipose tissue mass, lower serum leptin concentrations, and elevated plasma free fatty acid levels. Glucose and insulin tolerance tests revealed that FXR deficiency is associated with impaired glucose tolerance and insulin resistance. Moreover, whole-body glucose disposal during a hyperinsulinemic euglycemic clamp is decreased in FXR-deficient mice. In parallel, FXR deficiency alters distal insulin signaling, as reflected by decreased insulin-dependent Akt phosphorylation in both white adipose tissue and skeletal muscle. Whereas FXR is not expressed in skeletal muscle, it was detected at a low level in white adipose tissue in vivo and induced during adipocyte differentiation in vitro. Moreover, mouse embryonic fibroblasts derived from FXR-deficient mice displayed impaired adipocyte differentiation, identifying a direct role for FXR in adipocyte function. Treatment of differentiated 3T3-L1 adipocytes with the FXR-specific synthetic agonist GW4064 enhanced insulin signaling and insulin-stimulated glucose uptake. Finally, treatment with GW4064 improved insulin resistance in genetically obese ob/ob mice in vivo. Although the underlying molecular mechanisms remain to be unraveled, these results clearly identify a novel role of FXR in the regulation of peripheral insulin sensitivity and adipocyte function. This unexpected function of FXR opens new perspectives for the treatment of type 2 diabetes.
The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes ...for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities.
An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data.
A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as "severe" by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed "moderate" (37.3%), "mild" (14.1%) or "slight" (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training.
This survey, focusing on trainees' perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system.
Phase transitions in Li-ion electrode materials during (dis)charge are decisive for battery performance, limiting high-rate capabilities and playing a crucial role in the cycle life of Li-ion ...batteries. However, the difficulty to probe the phase nucleation and growth in individual grains is hindering fundamental understanding and progress. Here we use synchrotron microbeam diffraction to disclose the cycling rate-dependent phase transition mechanism within individual particles of LiFePO4, a key Li-ion electrode material. At low (dis)charge rates well-defined nanometer thin plate-shaped domains co-exist and transform much slower and concurrent as compared with the commonly assumed mosaic transformation mechanism. As the (dis)charge rate increases phase boundaries become diffuse speeding up the transformation rates of individual grains. Direct observation of the transformation of individual grains reveals that local current densities significantly differ from what has previously been assumed, giving new insights in the working of Li-ion battery electrodes and their potential improvements.
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