Tolerance of young allis shad Alosa alosa (Clupeidae) to oxy-thermic stress

The ecology of the young stages of allis shad Alosa alosa is poorly documented, although they can be exposed to many pressures during their freshwater phase and their downstream migration. When passing through systems such as the Gironde-Garonne-Dordogne watershed (GGD, SW France), they can be subjected to high temperatures and low levels of oxygen (hypoxia). The aim of this work is to assess the tolerance of young Alosa alosa at four ages (c. 10, 30, 60 and 85 days old) by challenging them to different temperatures (18, 22, 26 and 28°C) together with decreasing oxygen saturation levels (from 100% to 30%). Survival of the 10-day-old individuals was not influenced by oxy-thermic conditions, but high stress levels were detected and perhaps this age class was too fragile regarding the constraint of the experimental design. Survival at 30 and at 60 days old was negatively influenced by the highest temperatures tested alone (from 26°C and from 28°C, respectively) but no effect was detected at 85 days old up to 28°C. A combined effect of temperature and oxygen level was highlighted, with heat accelerating survival decrease when associated with oxygen level depletion: essentially, survival was critical (<50%) at 30 days old at temperature ≥22°C together with 30% O₂; at 60 days old, at temperature = 28°C with 30% O₂; at 85 days old, at temperature ≥26°C with ≤40% O₂. Tolerance to oxy-thermic pressures appeared to be greater among the migratory ages (60 and 85 days old) than among the 30-day-old group. Based on environmental data recorded in the GGD system and on our experimental results, an exploratory analysis allowed a discussion of the possible impact of past oxy-thermic conditions on the local population dynamics between 2005 and 2018. The oxy-thermic conditions that may affect Alosa alosa at ages when they migrate downstream (60 and 85 days old) were not frequently recorded in this period, except in cases of extreme episodes of heat together with hypoxia that occurred in some years, in summertime in the turbidity maximum zone of the Gironde estuary (particularly in the year 2006). Interestingly, oxy-thermic conditions that are likely to threaten the 30-day-old individuals occurred more frequently in the lower freshwater parts of the GGD system between the years 2005 and 2018. In the context of climate change, a general increase in temperature is predicted, as well as more frequent and severe hypoxic events, therefore we suggest that local Alosa alosa population recruitment could encounter critical oxy-thermic conditions more frequently in the future if no adaptive management of water resources occurs.     

Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis

The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

Ranging behaviour of roe deer in an experimental high-density population: Are females territorial?

We studied the ranging behaviour and spatial relationships between seven roe deer during more than 4 years in a partly wooded 14.2-ha enclosure. The animals (three young males, four adult females) were monitored with GPS telemetry collars. As expected, the surface area and overlap of the males’ bimonthly ranges decreased, and the distance between their arithmetic centres increased, as they became adult and, for two of them, territorial. Unexpectedly, females also tended to space out, the surface area and overlap of their bimonthly ranges being minimal in May to June, i.e. during the birth period. The distance between their arithmetic centres reached its maximum at the same time. Overlap between females’ ranges was consistently lower than those between males and females’ ranges, or between 1-year old males’ ranges. Our results raise the questions of female seasonal territoriality and of independence of the spacing systems of the two sexes in roe deer.     

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications

Based on immunomodulatory, osteogenic, and pro-angiogenic properties of adipose-derived stem cells (ASCs), this study aims to assess the safety and efficacy of ASC-derived cell therapies for clinical indications. Two autologous ASC-derived products were proposed to 17 patients who had not experienced any success with conventional therapies: (1) a scaffold-free osteogenic three-dimensional graft for the treatment of bone non-union and (2) a biological dressing for dermal reconstruction of non-healing chronic wounds. Safety was studied using the quality control of the final product (genetic stability, microbiological/mycoplasma/endotoxin contamination) and the in vivo evaluation of adverse events after transplantation. Feasibility was assessed by the ability to reproducibly obtain the final ASC-based product with specific characteristics, the time necessary for graft manufacturing, the capacity to produce enough material to treat the lesion, the surgical handling of the graft, and the ability to manufacture the graft in line with hospital exemption regulations. For 16 patients (one patient did not undergo grafting because of spontaneous bone healing), in-process controls found no microbiological/mycoplasma/endotoxin contamination, no obvious deleterious genomic anomalies, and optimal ASC purity. Each type of graft was reproducibly obtained without significant delay for implantation and surgical handling was always according to the surgical procedure and the implantation site. No serious adverse events were noted for up to 54 months. We demonstrated that autologous ASC transplantation can be considered a safe and feasible therapy tool for extreme clinical indications of ASC properties and physiopathology of disease.