Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wld^s allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.     

Shanidar 10: a Middle Paleolithic immature distal lower limb from Shanidar Cave, Iraqi Kurdistan

The analysis of the faunal remains from Shanidar Cave has identified an incomplete immature human distal leg and foot from the deepest levels of the Middle Paleolithic of Shanidar Cave, Iraq. The distal tibia, fibula, first metatarsal, and two tarsals, designated Shanidar 10, derive from a 1-2-year-old infant. The tibia exhibits a transverse line from a stress episode during the last quarter of its first year postnatal. The cross-sectional geometry of the tibial midshaft reveals modest cortical thickening and a level of diaphyseal robusticity similar to those of recent human infants of a similar developmental age.     

Selection of a remediation scenario for a diesel-contaminated site using LCA

Goal and Scope A comparison of in situ and ex situ treatment scenarios for a diesel-contaminated site was performed using an evolutive LCA. Treatment time along with primary (residual contamination left in soil or groundwater after treatment) and secondary (impacts due to remediation) environmental impacts were considered. The site under study had a light Non Aqueous Phase Liquid (LNAPL) thickness of up to 1 m, a diesel soil concentration of 10,500 mg/kg and a residual contamination in groundwater. Methods Four treatment scenarios to remove LNAPL and to treat soil and groundwater were compared: 1) pump and treat 2) bioslurping, bioventing and biosparging 3) bioslurping, bioventing and chemical oxidation and 4) ex situ treatment using biopiles. The technologies’ design was performed using simulation tools and analytical equations. The LCA was evaluated for each year of treatment. Environmental impacts were assessed using the U.S. EPA Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI) method. Results and Discussion The biological in situ scenario (2) showed the least primary and secondary impacts but its treatment time was more than 4 times longer than that obtained for the ex situ scenario (4). The ex situ scenario showed the best treatment time but its secondary impacts were significantly higher than those found for the biological in situ scenario due to the pavement of the treatment area. The combined biological and chemical in situ scenario (3) was the worst in terms of secondary impacts while the pump and treat scenario (1) was the worst in terms of primary impacts. Two scenarios were selected: one based upon low environmental impacts and the other on the fastest treatment time. Conclusions Even without excavation, an in situ treatment can generate more secondary impacts than an ex situ treatment. Low environmental impact scenarios require time while rapid treatment scenarios generate high environmental impacts. The selection of the best remediation scenario will depend on the site owner’s priority. Recommendations Better characterization factors for aggregated substances are required. This paper is openly accessible!     

Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset

Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood.     

DBA/2J Mice Are Susceptible to Diabetic Nephropathy and Diabetic Exacerbation of IOP Elevation

Some pathological manifestations of diabetes in the eye include retinopathy, cataracts and elevated intraocular pressure (IOP). Loss of retinal ganglion cells (RGCs) in non-proliferative stages of diabetic retinopathy and small increases in IOP in diabetic patients has raised the possibility that diabetes affects the development and progression of ocular hypertension and glaucoma. The Ins2^Akita mutation is known to cause diabetes and retinopathy on a C57BL/6J (B6) background by as early as 3 months of age. Here, the impact of the Akita mutation on glaucoma was assessed using DBA/2J (D2) mice, a widely used mouse model of ocular hypertension induced glaucoma. In D2.Ins2^Akita/+ mice, the contribution of diabetes to vascular permeability, IOP elevation, RGC loss, and glaucoma development was assessed. D2.Ins2^Akita/+ mice developed a severe diabetic nephropathy and early mortality between 6–8 months of age. This agrees with previous reports showing that the D2 background is more susceptible to diabetes than the B6 background. In addition, D2.Ins2^Akita/+ mice had vascular leakage, astrocyte reactivity and a significant increase in IOP. However no RGC loss and no anterograde axonal transport dysfunction were found at 8.5 months of age. Therefore, our data show that despite severe diabetes and an increased IOP compared to controls, RGCs do not lose axon transport or degenerate. This may be due to a DBA/2J-specific genetic modifier(s) that could provide novel and important avenues for developing new therapies for diabetic retinopathy and possibly glaucoma.     

The ins and outs of inflammatory cells in atheromata

Macrophage accumulation characterizes the formation of atherosclerotic plaques. Recent work in Nature Immunology (van Gils et?al., 2012) demonstrates that the neuroimmune guidance cue netrin-1 can retain macrophages in atherosclerotic lesions, thus promoting atherosclerosis.