Ultrastructural Variation in Enamel of Australian Marsupials

This paper initiates a survey of the enamel of fossil and extant Australian marsupials by scanning electron microscopy. Enamel was examined from 17 extant and 11 extinct marsupials. Assessment was made of prism packing pattern, prism course, tubule presence, tubule size and distribution. Values calculated were: prism diameter; prism axis ratio; cross-sectional prism area; cross-sectional ameloblast area; and numerical prism density. Three different prism packing arrangements were found for extant and fossil marsupials within the classical Pattern 2. The Pattern 1 arrangement found in three extant species was relatively unexpected given the general acceptance of Marsupialia as having Pattern 2 enamel. Attention is drawn to the variable loss of prism demarcation towards the outer enamel surface. The majority of both extant and fossil marsupials exhibited a simple radial prism course. Prism diameters were small ranging from 1.4 μm to 3.9 μm and prism densities were high, compared to those for human and multituberculate enamel. A significant inter-species variation was noted in the presence and size of enamel tubules. The absence of enamel tubules in the incisors of D. optatum, N. tedfordi and T. rostratus and the molar of W. wakefieldi was confirmed. Large bulbous spaces were found either along or at the termination of enamel tubules in some teeth of five fossil species: these spaces may represent the resting place of an ameloblast. We have found: a greater variation in prism packing patterns; a greater difference in characteristics studied between incisor and molar teeth; and a greater variety of tubule morphology than anticipated. There are signs that useful enamel ultrastructural characters are emerging to help ultimately with taxonomic investigations of Australian marsupials

Enamel of Yalkaparidon Coheni: Representative of a Distinctive Order of Tertiary Zalambdodont Marsupials

The enamel of an incisor and a premolar of Yalkaparidon coheni was examined by scanning electron microscopy in fractured and in sectioned, polished surfaces. The enamel of both teeth demonstrated: complete, ovoid and horse-shoe shaped prisms in a Pattern 2 arrangement; a simple parallel prism course; and, enamel tubules in abundance in the premolar but restricted to the innermost enamel in the incisor. Overall, the enamel ultrastructure supports the marsupial affiliation proposed for Yalkaparidon coheni but does not unambiguously ally it with any other order of marsupials. The observation of a significant ultrastructural difference between the anterior and posterior teeth of a marsupial emphasizes the need to sample both if available. In pursuing this, we report here also the lack of tubules in the anterior teeth of the extant Tarsipes rostratus. This together with a similar absence of typical marsupial tubules from the incisor of the extinct Yalkaparidon coheni, would suggest that the wombat is not the only surviving marsupial to have experimented so extensively with this particular structural feature. It is likely that further study will demonstrate an unexpected and relative lack of tubules in the incisor enamel of other fossil Australian marsupials

Tribo-oxidation of a brake friction couple under varying sliding conditions

This study explores a common parameter that is used to describe the energy input into a friction pairing in pin-on-disc investigations, the pv-value. The impacts of multiple sliding speed, v, and contact pressure, p, combinations were investigated while keeping their product, the pv-value at a constant level. The chosen tests for this study consisted of steady-state drag braking applications on a small-scale test bench. The actual contact area on the friction material's surface was measured after the tests and correlated to the steady-state temperature, T, that was reached during testing. The tribological interface showed sensitivity towards the different sliding and loading conditions including a shift in oxidising states of the iron contents of the friction couples. The sliding and loading conditions were reversed after the transition of oxidising states in order to investigate their impact. The results show that the oxidising states dynamically react to the operating conditions, but the overall frictional performance of the system can remain at an altered level due to enduring changes in the actual contact area and the thermal response of the friction couple with the transition in oxidising states

What is damaging the kidney in lupus nephritis?

Despite marked improvements in the survival of patients with severe lupus nephritis over the past 50 years, the rate of complete clinical remission after immune suppression therapy i

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Inducible Nitric Oxide Synthase Inhibitor SD-3651 Reduces Proteinuria in MRL/lpr Mice Deficient in the NOS2 Gene

Several studies have demonstrated the effectiveness of arginine analog nitric oxide synthase (NOS) inhibitor therapy in preventing and treating murine lupus nephritis. However, MRL/MpJ-FASlpr (MRL/lpr) mice lacking afunctional NOS2 (inducible NOS [iNOS]) gene (NOS2−/−) develop proliferative glomerulonephritis in a fashion similar to their wild-type (wt) littermates. This finding suggests that the effect of arginine analog NOS inhibitors is through a non-iNOS-mediated mechanism. This study was designed to address this hypothesis.NOS2−/− mice were given either vehicle or a NOS inhibitor (SD-3651) to determine if pharmacological NOS inhibition prevented glomerulonephritis, using wt mice as positive controls. Urine was collected fortnightly to measure albumin. At the time of full disease expression in wt mice, all mice were killed, and renal tissue was examined for light, immunofluorescence, and electron microscopic evidence of disease. Serum was analyzed for anti-double-stranded DNA antibody production.NOS2−/− mice had higher serum anti-double-stranded DNA antibody antibody levels than those of wt mice. SD-3651 therapy reduced proteinuria, glomerular immunoglobulin G deposition, and electron microscopic evidence of podocytopathy and endothelial cell swelling without affecting proliferative lesions by light microscopy.These studies confirm that genetic iNOS deficiency alone is insufficient to prevent proliferative glomerulonephritis and suggest that iNOS activity may inhibit autoantibody production. These results also suggest that SD-3651 therapy acts via a non-iNOS-mediated mechanism to prevent endothelial cell and podocyte pathology. Studies that elucidate this mechanism could provide a useful drug target for the treatment of nephritis

Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b+ CD68+ macrophages in skin lesions

Background: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages. Objectives: To elucidate associations between psoriasis and conventional CV risk factors. Methods: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin. Results: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45 + CD11b + leukocytes. CD11b + cell density correlated with circulation MPO levels. Conclusion: Lesional skin CD11b + leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b + cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease