Realizing modules over the homology of a DGA

Let A be a DGA over a field and X a module over H_*(A). Fix an $A_\infty$-structure on H_*(A) making it quasi-isomorphic to A. We construct an equivalence of categories between A_{n+1}-module structures on X and length n Postnikov systems in the derived category of A-modules based on the bar resolution of X. This implies that quasi-isomorphism classes of A_n-structures on X are in bijective correspondence with weak equivalence classes of rigidifications of the first n terms of the bar resolution of X to a complex of A-modules. The above equivalences of categories are compatible for different values of n. This implies that two obstruction theories for realizing X as the homology of an A-module coincide.Comment: 24 page

Prospective, Randomized, Controlled Trial of Tissue Adhesive (2-Octylcyanoacrylate) vs Standard Wound Closure Techniques for Laceration Repair

Objective: To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations. Methods: A prospective, randomized, controlled clinical trial enrolled consecutive patients >1 year of age with non-bite, non-crush-induced lacerations who presented 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale. Results : There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 ± 19.4 mm vs standard techniques, 82.5 ± 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67). Conclusions: Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75580/1/j.1553-2712.1998.tb02590.x.pd

661W photoreceptor cell line as a cell model for studying retinal ciliopathies

Copyright © 2019 Wheway, Nazlamova, Turner and Cross. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The retina contains several ciliated cell types, including the retinal pigment epithelium (RPE) and photoreceptor cells. The photoreceptor cilium is one of the most highly modified sensory cilia in the human body. The outer segment of the photoreceptor is a highly elaborate primary cilium, containing stacks or folds of membrane where the photopigment molecules are located. Perhaps unsurprisingly, defects in cilia often lead to retinal phenotypes, either as part of syndromic conditions involving other organs, or in isolation in the so-called retinal ciliopathies. The study of retinal ciliopathies has been limited by a lack of retinal cell lines. RPE1 retinal pigment epithelial cell line is commonly used in such studies, but the existence of a photoreceptor cell line has largely been neglected in the retinal ciliopathy field. 661W cone photoreceptor cells, derived from mouse, have been widely used as a model for studying macular degeneration, but not described as a model for studying retinal ciliopathies such as retinitis pigmentosa. Here, we characterize the 661W cell line as a model for studying retinal ciliopathies. We fully characterize the expression profile of these cells, using whole transcriptome RNA sequencing, and provide this data on Gene Expression Omnibus for the advantage of the scientific community. We show that these cells express the majority of markers of cone cell origin. Using immunostaining and confocal microscopy, alongside scanning electron microscopy, we show that these cells grow long primary cilia, reminiscent of photoreceptor outer segments, and localize many cilium proteins to the axoneme, membrane and transition zone. We show that siRNA knockdown of cilia genes Ift88 results in loss of cilia, and that this can be assayed by high-throughput screening. We present evidence that the 661W cell line is a useful cell model for studying retinal ciliopathies

Isoflavone glycosides: Synthesis and evaluation as α-glucosidase inhibitors

On the basis of the structure of 4′,7,8-trihydroxyisoflavone 7-O-α-D-arabinofuranoside (namely A-76202, 1), a Rhodococcus metabolite showing potent inhibitory activities against the α-glucosidases of rat liver microsome (IC 50 = 0.46 ng/mL), 26 analogs, each with minor variations at the sugar moiety and the isoflavone A and B rings, were readily synthesized. Notably, a new and efficient method was developed for the divergent synthesis of the B-ring congeners of the isoflavone glycosides by using Suzuki-Miyaura coupling as the final step. Modifications at the sugar moiety and the isoflavone A ring significantly diminish the activity, whereas variations at the B ring are largely tolerated for retaining the potent α-glucosidase inhibitory activity. © Wiley-VCH Verlag GmbH & Co. KGaA, 2008.postprin

Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies

AbstractMutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR1–19 and RPGRORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors

The profile of executive function in OCD hoarders and hoarding disorder

Hoarding disorder is a new mental disorder in DSM-5. It is classified alongside OCD and other presumably related disorders in the Obsessive-Compulsive and Related Disorders chapter. We examined cognitive performance in two distinct groups comprising individuals with both OCD and severe hoarding, and individuals with hoarding disorder without comorbid OCD. Participants completed executive function tasks assessing inhibitory control, cognitive flexibility, spatial planning, probabilistic learning and reversal and decision making. Compared to a matched healthy control group, OCD hoarders showed significantly worse performance on measures of response inhibition, set shifting, spatial planning, probabilistic learning and reversal, with intact decision making. Despite having a strikingly different clinical presentation, individuals with only hoarding disorder did not differ significantly from OCD hoarders on any cognitive measure suggesting the two hoarding groups have a similar pattern of cognitive difficulties. Tests of cognitive flexibility were least similar across the groups, but differences were small and potentially reflected subtle variation in underlying brain pathology together with psychometric limitations. These results highlight both commonalities and potential differences between OCD and hoarding disorder, and together with other lines of evidence, support the inclusion of the new disorder within the new Obsessive-Compulsive and Related Disorders chapter in DSM-5

Clinical course of cone dystrophy caused by mutations in the RPGR gene

Contains fulltext : 97720.pdf (publisher's version ) (Closed access)BACKGROUND: Mutations in the RPGR gene predominantly cause rod photoreceptor disorders with a large variability in clinical course. In this report, we describe two families with mutations in this gene and cone involvement. METHODS: We investigated an X-linked cone dystrophy family (1) with 25 affected males, 25 female carriers, and 21 non-carriers, as well as a small family (2) with one affected and one unaffected male. The RPGR gene was analyzed by direct sequencing. All medical records were evaluated, and all available data on visual acuity, color vision testing, ophthalmoscopy, fundus photography, fundus autofluorescence, Goldmann perimetry, SD-OCT, dark adaptation, and full-field electroretinography (ERG) were registered. Cumulative risks of visual loss were studied with Kaplan-Meier product-limit survival analysis. RESULTS: Both families had a frameshift mutation in ORF15 of the RPGR gene; family 1 had p.Ser1107ValfsX4, and family 2 had p.His1100GlnfsX10. Mean follow up was 13 years (SD 10). Virtually all affected males showed reduced photopic and normal scotopic responses on ERG. Fifty percent of the patients had a visual acuity of <0.5 at age 35 years (SE 2.2), and 75% of the patients was legally blind at age 60 years (SE 2.3). Female carriers showed no signs of ocular involvement. CONCLUSIONS: This report describes the clinical course and visual prognosis in two families with cone dystrophy due to RPGR mutations in the 3' terminal region of ORF15. Remarkable features were the consistent, late-onset phenotype, the severe visual outcome, and the non-expression in female carriers. Expression of RPGR mutations in this particular region appears to be relatively homogeneous and predisposed to cones