Delta and Hairy establish a periodic prepattern that positions sensory bristles in Drosophila legs

AbstractIn vertebrates and invertebrates, spatially defined proneural gene expression is an early and essential event in neuronal patterning. In this study, we investigate the mechanisms involved in establishing proneural gene expression in the primordia of a group of small mechanosensory bristles (microchaetae), which on the legs of the Drosophila adult are arranged in a series of longitudinal rows along the leg circumference. In prepupal legs, the proneural gene achaete (ac) is expressed in longitudinal stripes, which comprise the leg microchaete primordia. We have previously shown that periodic ac expression is partially established by the prepattern gene, hairy, which represses ac expression in four of eight interstripe domains. Here, we identify Delta (Dl), which encodes a Notch (N) ligand, as a second leg prepattern gene. We show that Hairy and Dl function concertedly and nonredundantly to define periodic ac expression. We also explore the regulation of periodic hairy expression. In prior studies, we have found that expression of two hairy stripes along the D/V axis is induced in response to the Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) morphogens. Here, we show that expression of two other hairy stripes along the orthogonal A/P axis is established through a distinct mechanism which involves uniform activation combined with repressive influences from Dpp and Wg. Our findings allow us to formulate a general model for generation of periodic pattern in the adult leg. This process involves broad and late activation of ac expression combined with refinement in response to a prepattern of repression, established by Hairy and Dl, which unfolds progressively during larval and early prepupal stages

Hox genes modulate the proneural prepattern to generate morphological diversity in Drosophila adult legs.

Hox genes modulate the proneural prepattern to generate morphological diversity in Drosophila adult legs

Inverted flap technique for a large traumatic macular hole with choroidal rupture and subretinal hemorrhage

Large traumatic macular holes (TMHs) tend to be irregular and have a variable predictability. The inverted flap technique makes use of remnants of internal limiting membrane (ILM) at the periphery of the MH. The peeled-off ILM contains Müller cell fragments which can induce gliosis and help in closure of MH. We operated on a case of large TMH (~899 μ minimum linear diameter) with choroidal rupture and subretinal hemorrhage in a young female with the inverted flap technique of ILM peeling and observed successful closure of the MH. The excellent anatomical and surgical results achieved in our case seem to suggest this to be a safe and effective surgical manoeuvre for such cases

Idiopathic Myointimal Hyperplasia of Mesenteric Veins of the Ileum and Colon in a Patient with Crohn’s Disease: A Case Report and Brief Review of the Literature

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare disease characterized by intimal smooth muscle proliferation, leading to the thickening of small to medium-sized mesenteric veins. This vascular disease mimics inflammatory bowel disease (IBD) clinically and endoscopically, while showing ischemic mucosal changes without the classic features of IBD on biopsy. Given the mixed picture, this entity is frequently misdiagnosed. Surgical resection of the diseased bowel segment reveals the true etiology of the pathology and is curative. We describe a case of a 59-year-old man with a long-standing history of Crohn’s disease refractory to medical therapy and status after multiple small bowel resections. The patient underwent a subtotal abdominal colectomy with pathology showing dense, indurated mesenteric adipose tissue, significant muscularis propria hypertrophy, and myointimal hyperplasia of the mesenteric veins in a peri-ileal and pericolic distribution, as confirmed by elastin stain. No evidence of mucosal ischemic changes or findings of chronicity or acuity were seen. IMHMV, a rare disease with a mixed presentation, poses a significant diagnostic challenge to clinicians and pathologists

Bimanual 25-gauge chandelier technique for direct perfluorocarbon liquid-silicone oil exchange in retinal detachments associated with giant retinal tear

Direct perfluorocarbon liquid (PFCL)-silicone oil exchange presents its own set of challenges in the micro incision vitreous surgery era. We propose a simple bimanual technique to circumvent this problem. Thirteen eyes of patients with retinal detachment associated with giant retinal tears underwent vitrectomy followed by self-retaining endo illuminator (Chandelier) assisted direct PFCL-silicone exchange. No intra or postoperative complications related to the surgical technique were noted. All patients had attached retinas and satisfactory visual recovery at 6 months. Direct bimanual PFCL silicone oil exchange using a Chandelier seems to be a safe and effective technique

Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost

Background: Over 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic machine perfusion to identify transplantable livers among those currently discarded. Study Design: A series of 21 discarded human livers underwent viability assessment during normothermic machine perfusion. Cross-sectional analysis of the Scientific Registry of Transplant Recipients database and cost analysis was performed to extrapolate the case series to national experience. Results: 21 discarded human livers were included in the perfusion cohort. 11 of 20 (55%) eligible grafts met viability criteria for transplantation. Grafts in the perfusion cohort had a similar donor risk index compared with discarded grafts (n = 1402) outside of New England in 2017 and 2018 (median [IQR]: 2.0 [1.5, 2.4] vs. 2.0 [1.7, 2.3], P =.40). 705 (IQR 677-741) livers were discarded annually in the United States since 2005, translating to the potential for 398 additional transplants nationally. The median cost to identify a transplantable graft with machine perfusion was $28,099 USD. Conclusions: Normothermic machine perfusion of discarded livers could identify a significant number of transplantable grafts, significantly improving access to liver transplantation

Molecular magnetic resonance imaging of liver inflammation using an oxidatively activated probe

Background &amp; Aims: Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify liver inflammation has been underdeveloped. The inflammatory liver microenvironment is aberrantly oxidising owing in part to reactive oxygen species generated by myeloid leucocytes. We hypothesised that magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of liver inflammation. Methods: A mouse model of drug-induced liver injury was generated through intraperitoneal injection of a hepatoxic dose of acetaminophen. A mouse model of steatohepatitis was generated via a choline-deficient, l-amino acid defined high-fat diet (CDAHFD). Images were acquired dynamically before and after intravenous injection of Fe-PyC3A. The contrast agent gadoterate meglumine was used as a non-oxidatively activated negative control probe in mice fed CDAHFD. The (post-pre) Fe-PyC3A injection change in liver vs. muscle contrast-to-noise ratio (ΔCNR) recorded 2 min post-injection was correlated with liver function test values, histologic scoring assigned using the NASH Clinical Research Network criteria, and intrahepatic myeloid leucocyte composition determined by flow cytometry. Results: For mice receiving i.p. injections of acetaminophen, intrahepatic neutrophil composition correlated poorly with liver test values but positively and significantly with ΔCNR (r = 0.64, p <0.0001). For mice fed CDAHFD, ΔCNR generated by Fe-PyC3A in the left lobe was significantly greater in mice meeting histologic criteria strongly associated with a diagnosis NASH compared to mice where histology was consistent with likely non-NASH (p = 0.0001), whereas no differential effect was observed using gadoterate meglumine. In mice fed CDAHFD, ΔCNR did not correlate strongly with fractional composition of any specific myeloid cell subpopulation as determined by flow cytometry. Conclusions: Magnetic resonance imaging using Fe-PyC3A merits further evaluation as a non-invasive biomarker for liver inflammation. Impact and implications: Non-invasive tests to diagnose and measure liver inflammation are underdeveloped. Inflammatory cells such as neutrophils release reactive oxygen species which creates an inflammatory liver microenvironment that can drive chemical oxidation. We recently invented a new class of magnetic resonance imaging probe that is made visible to the scanner only after chemical oxidation. Here, we demonstrate how this imaging technology could be applied as a non-invasive biomarker for liver inflammation