Ataxia Telangiectasia Mutated Dysregulation Results in Diabetic Retinopathy

Ataxia telangiectasia mutated (ATM) acts as a defense against a variety of bone marrow (BM) stressors. We hypothesized that ATM loss in BM-hematopoietic stem cells (HSCs) would be detrimental to both HSC function and microvascular repair while sustained ATM would be beneficial in disease models of diabetes. Chronic diabetes represents a condition associated with HSC depletion and inadequate vascular repair. Gender mismatched chimeras of ATM(-/-) on wild type background were generated and a cohort were made diabetic using streptozotocin (STZ). HSCs from the STZ-ATM(-/-) chimeras showed (a) reduced self-renewal; (b) decreased long-term repopulation; (c) depletion from the primitive endosteal niche; (d) myeloid bias; and (e) accelerated diabetic retinopathy (DR). To further test the significance of ATM in hematopoiesis and diabetes, we performed microarrays on circulating angiogenic cells, CD34(+) cells, obtained from a unique cohort of human subjects with long-standing (>40 years duration) poorly controlled diabetes that were free of DR. Pathway analysis of microarrays in these individuals revealed DNA repair and cell-cycle regulation as the top networks with marked upregulation of ATM mRNA compared with CD34(+) cells from diabetics with DR. In conclusion, our study highlights using rodent models and human subjects, the critical role of ATM in microvascular repair in DR

Hematopoietic stem/progenitor involvement in retinal microvascular repair during diabetes: Implications for bone marrow rejuvenation

The widespread nature of diabetes affects all organ systems of an individual including the bone marrow. Long-term damage to the cellular and extracellular components of the bone marrow leads to a rapid decline in the bone marrow-hematopoietic stem/progenitor cells (HS/PCs) compartment. This review will highlight the importance of bone marrow microenvironment in maintaining bone marrow HS/PC populations and the contribution of these key populations in microvascular repair during the natural history of diabetes. The autonomic nervous system can initiate and propagate bone marrow dysfunction in diabetes. Systemic pharmacological strategies designed to protect the bone marrow-HS/PC population from diabetes induced-oxidative stress and advanced glycation end product accumulation represent a new approach to target diabetic retinopathy progression. Protecting HS/PCs ensures their participation in vascular repair and reduces the risk of vasogdegeneration occurring in the retina

The Vehicle, Fall 2003

Table of Contents Blame It on My BirthsignMichael Doizanpage 4 Like a BanjoKaitlyn Kingstonpage 6 A BubbleMaria Santoyopage 7 UntitledLiz Toyntonpage 8 She Said It Was Stuck in the FenceGreg Holdenpage 11 Thanksgiving Table CharactersKrystal Heringpage 12 This Is My LandKorah Winnpage 13 Bleeding HeartsKaitlyn Kingstonpage 14 SoldierEmily Rapppage 17 HomelessLaTasha Harrispage 18 InfinitiLindsey Nawojskipage 19 Gone Until ForeverAndy Whytepage 20 On My WayKristin Bornpage 27 GloryJay Popepage 28 Untitled (1)Trevor Moorepage 29 Nature\u27s MoratoriumMatt McCarthypage 29 Untitled (2)Trevor Moorepage 30 Eternal ChildAmy Towerypage 31 FingersJosh Sopiarzpage 31 She Likes JazzMario Podeschipage 32 Back Alley FarmsScott E. Lutzpage 33 Biographiespage 35https://thekeep.eiu.edu/vehicle/1078/thumbnail.jp

Subgrade Improvement by Sand Compaction Pile

Expansive soil becomes soft on wetting and losses its strength, resulting in differential settlement. Vast areas, particularly coastal regions, are covered with thick soft clay deposits having very low shear strength posing difficulty to use as subgrade. Such soils were avoided or proper soil improving techniques need to be adopted. Ground improvement techniques are normally preferred for economy and one of which is Sand Compaction Pile (SCP) method. SCP is widely adopted to improve weak/lose ground to achieve adequate bearing capacity and reduce the settlement. In this study the load carrying capacity of soft clay with and without compaction pile by M sand is tested using CBR test. Also, the effect of variation in the pattern of installation and spacing between the piles on the load-settlement behavior was examined. The test results indicate that compaction piles decreases the subgrade settlement and the triangular pattern with 2.5D spacing is most the effective technique. The permeability results reveal an added advantage of SCP, by draining the moisture that might have clogged between the subgrade and base course.

Changing the landscape for type 1 diabetes: the first step to prevention

Over several decades, studies have described the progression of autoimmune diabetes, from the first appearance of autoantibodies until, and after, the diagnosis of clinical disease with hyperglycaemia and insulin dependence. Despite the improved management of type 1 diabetes with exogenous insulin, most patients do not meet clinical glycaemic goals, and diabetes remains an important medical problem that affects children and adults. Clinical and preclinical studies have suggested strategies to prevent the diagnosis of type 1 diabetes in people at risk, but the outcomes of previous clinical trials have not met their primary endpoints of disease prevention or delay. The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease. This Series paper discusses how this clinical achievement raises new questions about for whom, and when, immunological strategies might be developed to prevent type 1 diabetes, and how to achieve this goal