Giraffe translocation population viability analysis

Most populations of giraffes have declined in recent decades, leading to the recent IUCN decision to upgrade the species to Vulnerable status, and some subspecies to Endangered. Translocations have been used as a conservation tool to re-introduce giraffes to previously occupied areas or establish new populations, but guidelines for founding populations are lacking. To provide general guidelines for translocation projects regarding feasibility, we simulated various scenarios of translocated giraffe populations to identify viable age and sex distributions of founding populations using population viability analysis (PVA) implemented in Vortex software. We explored the parameter space for demography and the genetic load, examining how variation in founding numbers and sex ratios affected 100 yr probability of population extinction and genetic diversity. We found that even very small numbers of founders (N ≤ 10 females) can appear to be successful in the first decades due to transient positive population growth, but with moderate population growth rate and moderate genetic load, long-term population viability (probability of extinction 95% genetic diversity of the source population in an isolated population, 50 females and 5 males are recommended to compose the founding population. Sensitivity analyses revealed first-year survival and reproductive rate were the simulation parameters with the greatest proportional influence on probability of extinction and genetic diversity. These simulations highlight important considerations for translocation success and data gaps including true genetic load in wild giraffe populations

L(+) and D(−) Lactate Are Increased in Plasma and Urine Samples of Type 2 Diabetes as Measured by a Simultaneous Quantification of L(+) and D(−) Lactate by Reversed-Phase Liquid Chromatography Tandem Mass Spectrometry

Background. Plasma and urinary levels of D-lactate have been linked to the presence of diabetes. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition. Methods. D- and L-lactate were quantified using ultraperformance liquid chromatography tandem mass spectrometry with labelled internal standard. Samples were derivatized with diacetyl-L-tartaric anhydride and separated on a C18-reversed phase column. D- and L-lactate were analysed in plasma and urine of controls, patients with inflammatory bowel disease (IBD), and patients with type 2 diabetes (T2DM). Results. Quantitative analysis of D- and L-lactate was achieved successfully. Calibration curves were linear (r2 > 0.99) over the physiological and pathophysiological ranges. Recoveries for urine and plasma were between 96% and 113%. Inter- and intra-assay variations were between 2% and 9%. The limits of detection of D-lactate and L-lactate in plasma were 0.7 μmol/L and 0.2 μmol/L, respectively. The limits of detection of D-lactate and L-lactate in urine were 8.1 nmol/mmol creatinine and 4.4 nmol/mmol creatinine, respectively. Plasma and urinary levels of D- and L-lactate were increased in patients with IBD and T2DM as compared with controls. Conclusion. The presented method proved to be suitable for the quantification of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker

Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS

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Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: a technical feasibility study by EuroClonality-NGS

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Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

Abstract Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening:The Maastricht Study

Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (s 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (s 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction</p

Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility

Scope: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown. Methods and results: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (~1.8–6.9 fold increased protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations. Conclusion: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.Peer reviewe