Die Welt nach Covid-19

Der Autor aus Indien beschreibt, in welcher Situation sich die Welt aufgrund der exzessiven und ungerechtfertigten Maßnahmen befindet, die ergriffen wurden, um die Verbreitung von Covid-19 aufzuhalten. Er zeigt, wie die Pandemie insbesondere die von sozialer Armut betroffenen Gemeinschaften beeinflusst. Er konzentriert sich auf die ausgebeuteten Gemeinschaften Indiens, die die Mehrheit der Bevölkerung ausmachen. Neben Gemeinschaften, die als „Unberührbare“ von der Hindu-Religion gebrandmarkt werden, gehören dazu weitere Kasten und Gruppen, die sozialer Ächtung und Stigmatisierung ausgesetzt sind. Im Zuge der jüngsten Bewegungen für soziale Gerechtigkeit im Land haben diese Gemeinschaften, die die Mehrheit der Bevölkerung Indiens ausmachen, begonnen, sich selbst als „Bahujan“ — Menschen in der Mehrheit — zu bezeichnen, als Ausdruck ihrer Solidarität. „Bahujan“ ist ein konzeptioneller Begriff, der erstmals vor etwa 2.500 Jahren in den Lehren Buddhas Erwähnung findet. Es ist ein globaler Begriff, der die Einheit der Mehrheit betont und alle ausgebeuteten und benachteiligten Gruppen umfasst, einschließlich derjenigen, die Opfer von Rassismus und Geschlechterdiskriminierung sind. Das Wort „Bahujan“ wird im Artikel in diesem Zusammenhang und in dieser Bedeutung verwendet. [This article was first published in Hindi under the title "कोविड पश्चात दुनिया और बहुजन". Ekta News and Features did the English translation of this article under the title "post covid world and Bahujan". It was translated into German by Sabine Amann from the volunteer Rubikon translation team and edited by the volunteer Rubikon proofreading team.

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.BackgroundIt is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown.MethodsWe morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1mg/kg/day).ResultsEight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals.ConclusionsThe ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content. Conclusion Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling

Multi-annual and multi-decadal evolution of sediment accretion in a saltmarsh of the French Atlantic coast: Implications for carbon sequestration

Coastal marshes offer natural solutions for adapting to and mitigating the effects of climate change and sea level rise. However, the resilience of the marsh physical system and, with it, the ecosystem services that it provides, is largely site specific. This calls for the increase in the spatial cover of coastal marsh studies in order to assess the controlling factors of marsh evolution, and their long-term carbon storage capacities. Here, we study the spatio-temporal variations in sedimentation rates and organic carbon (OC) sequestration capacity of the macrotidal minerogenic saltmarshes in Aiguillon Bay, belonging to one of the largest French coastal marshes. Supported by aerial photographs and satellite image analysis, we first show that saltmarshes of the Aiguillon Bay have prograded at very high rates, up to 14 m yr−1 since 1950. Sediment accumulation rates (SAR) were estimated at both multi-annual to multi-decadal scales based on two approaches: (i) LiDAR-based digital elevation models from multiple acquisition dates (2010–2021); and (ii) depth profiles of 210Pb in excess and 137Cs in sediment cores collected along cross-shore transects in the saltmarshes. Long-term SAR range from 0.8 to 2.2 cm yr−1 and are among the highest reported worldwide for equivalent systems. The positive accretion balance (accretion rate minus local sea-level rise rate) provides important clues on marsh resilience suggesting that the Aiguillon Bay is currently able to adapt to rising sea level. Despite relatively low organic carbon content (1.3–6.0%), high SAR leads to high carbon sequestration rates (99–345 gC m−2 yr−1; or a mean value of 2.5 Mg C ha−1 yr−1). The isotopic signature of sediment OC reveals a significant and rapid decomposition of organic material in surface cores, while allochthonous sediment of marine origin dominates the signature of chemically-stable OC of marsh sediments. This implies that the carbon sequestration capacity of minerogenic saltmarshes, such as those of the Pertuis Charentais, also depends upon the wealth of adjacent coastal environments through high sediment supply and primary productivity.Evolution de l'identité patrimoniale des marais des Pertuis Charentais en réponse à l'aléa de submersion marin

Activin promotes skin carcinogenesis by attraction and reprogramming of macrophages.

Activin has emerged as an important player in different types of cancer, but the underlying mechanisms are largely unknown. We show here that activin overexpression is an early event in murine and human skin tumorigenesis. This is functionally important, since activin promoted skin tumorigenesis in mice induced by the human papillomavirus 8 oncogenes. This was accompanied by depletion of epidermal γδ T cells and accumulation of regulatory T cells. Most importantly, activin increased the number of skin macrophages via attraction of blood monocytes, which was prevented by depletion of CCR2-positive monocytes. Gene expression profiling of macrophages from pre-tumorigenic skin and bioinformatics analysis demonstrated that activin induces a gene expression pattern in skin macrophages that resembles the phenotype of tumor-associated macrophages in different malignancies, thereby promoting angiogenesis, cell migration and proteolysis. The functional relevance of this finding was demonstrated by antibody-mediated depletion of macrophages, which strongly suppressed activin-induced skin tumor formation. These results demonstrate that activin induces skin carcinogenesis via attraction and reprogramming of macrophages and identify novel activin targets involved in tumor formation

Levels of brain-derived neurotrophic factor in patients with multiple sclerosis

Objective To determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS. Methods Using a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model. Results In total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004). Interpretation We conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level

Negative emissions-Part 2 : Costs, potentials and side effects

Peer reviewedPublisher PD

Fingolimod in children with Rett syndrome: the FINGORETT study

Background Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy. This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case–control design. Methods At the University of Basel Children’s Hospital, Basel, Switzerland, children with RS were included if they were older than 6 years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation. Participants were observed 6 months before and after treatment and received 12 months of fingolimod treatment. Serum samples of 50 children without RS served as reference for brain-derived neurotrophic factor (BDNF) measurements. Primary outcome measures were safety and efficacy, the latter measured by change in levels of BDNF in serum/CSF (cerebrospinal fluid) and change in deep gray matter volumes measured by magnetic resonance imaging (MRI). Secondary outcome measure was efficacy measured by change in clinical scores [Vineland Adaptive Behaviour Scale (VABS), Rett Severity Scale (RSSS) and Hand Apraxia Scale (HAS)]. Results Six children with RS (all girls, mean and SD age 11.3 ± 3.1 years) were included. Serum samples of 50 children without RS (25 females, mean and SD age 13.5 ± 3.9 years) served as reference for BDNF measurements. No serious adverse events occurred. Primary and secondary outcome measures were not met. CSF BDNF levels were associated with all clinical scores: RSSS (estimate − 0.04, mult.effect 0.96, CI [0.94; 0.98], p = 0.03), HAS (estimate − 0.09, mult.effect 0.91, CI [0.89; 0.94], p <  0.01) and VABS (communication: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/daily living: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/social skills: estimate 0.07, mult.effect 1.08, CI [1.05; 1.11], p < 0.01/motoric skills: estimate 0.04, mult.effect 1.04, CI [1.03; 1.06], p = 0.02). Conclusions In children with RS, treatment with fingolimod was safe. The study did not provide supportive evidence for an effect of fingolimod on clinical, laboratory, and imaging measures. CSF BDNF levels were associated with clinical scores, indicating a need to further evaluate its potential as a biomarker for RS. This finding should be further validated in independent patient groups

A Novel Acyl-CoA Beta-Transaminase Characterized from a Metagenome

BACKGROUND: Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia. METHODOLOGY/PRINCIPAL FINDINGS: We applied the gene context approach to assembled sequences of the metagenome of the anaerobic digester of a municipal wastewater treatment plant, and identified a new gene which may participate in an alternative pathway of lysine fermentation. CONCLUSIONS: We characterized a novel, unique aminotransferase that acts exclusively on Coenzyme A (CoA) esters, and proposed a variant route for lysine fermentation. Results suggest that most of the lysine fermenting organisms use this new pathway in the digester. Its presence in organisms representative of two distinct bacterial divisions indicate that it may also be present in other organisms

Hedgehog partial agonism drives warburg-lie metabolism in muscle and brown fat

Diabetes, obesity, and cancer affect upward of 15% of the world&rsquo;s population. Interestingly, all three diseases juxtapose dysregulated intracellular signaling with altered metabolic state. Exactly which genetic factors define stable metabolic set points in vivo remains poorly understood. Here, we show that hedgehog signaling rewires cellular metabolism. We identify a cilium-dependent Smo-Ca2+-Ampk axis that triggers rapid Warburg-like metabolic reprogramming within minutes of activation and is required for proper metabolic selectivity and flexibility. We show that Smo modulators can uncouple the Smo-Ampk axis from canonical signaling and identify cyclopamine as one of a new class of &ldquo;selective partial agonists,&rdquo; capable of concomitant inhibition of canonical and activation of noncanonical hedgehog signaling. Intriguingly, activation of the Smo-Ampk axis in vivo drives robust insulin-independent glucose uptake in muscle and brown adipose tissue. These data identify multiple noncanonical endpoints that are pivotal for rational design of hedgehog modulators and provide a new therapeutic avenue for obesity and diabetes.<br /