397 research outputs found

    Deformation theory of objects in homotopy and derived categories III: abelian categories

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    This is the third paper in a series. In part I we developed a deformation theory of objects in homotopy and derived categories of DG categories. Here we show how this theory can be used to study deformations of objects in homotopy and derived categories of abelian categories. Then we consider examples from (noncommutative) algebraic geometry. In particular, we study noncommutative Grassmanians that are true noncommutative moduli spaces of structure sheaves of projective subspaces in projective spaces.Comment: Alexander Efimov is a new co-author of this paper. Besides some minor changes, a new part (part 3) about noncommutative Grassmanians was adde

    Faecal microbiota in dogs with multicentric lymphoma

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    Malignant lymphoma B-cell type is the most common canine haematopoietic malignancy. Changes in intestinal microbiota have been implicated in few types of cancer in humans. The aim of this prospective and case-control study was to determine differences in faecal microbiota between healthy control dogs and dogs with multicentric lymphoma. Twelve dogs affected by multicentric, B-cell, stage III-IV lymphoma, and 21 healthy dogs were enrolled in the study. For each dog, faecal samples were analysed by Illumina sequencing of 16S rRNA genes and quantitative PCR (qPCR) for selected bacterial groups. Alpha diversity was significant lower in lymphoma dogs. Principal coordinate analysis plots showed different microbial clustering (P = .001) and linear discriminant analysis effect size revealed 28 differentially abundant bacterial groups in lymphoma and control dogs. The qPCR analysis showed significant lower abundance of Faecalibacterium spp. (q < .001), Fusobacterium spp. (q = .032), and Turicibacter spp. (q = .043) in dogs with lymphoma compared with control dogs. On the contrary, Streptococcus spp. was significantly higher in dogs with lymphoma (q = .041). The dysbiosis index was significantly higher (P < .0001) in dogs with lymphoma. In conclusion, both sequencing and qPCR analyses provided a global overview of faecal microbial communities and showed significant differences in the microbial communities of dogs presenting with multicentric lymphoma compared with healthy control dogs.dog

    Reciprocal regulation of airway rejection by the inducible gas-forming enzymes heme oxygenase and nitric oxide synthase

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    Obliterative bronchiolitis (OB) develops insidiously in nearly half of all lung transplant recipients. Although typically preceded by a CD8+ T cell–rich lymphocytic bronchitis, it remains unresponsive to conventional immunosuppression. Using an airflow permissive model to study the role of gases flowing over the transplanted airway, it is shown that prolonged inhalation of sublethal doses of carbon monoxide (CO), but not nitric oxide (NO), obliterate the appearance of the obstructive airway lesion. Induction of the enzyme responsible for the synthesis of CO, heme oxygenase (Hmox) 1, increased carboxyhemoglobin levels and suppressed lymphocytic bronchitis and airway luminal occlusion after transplantation. In contrast, zinc protoporphyrin IX, a competitive inhibitor of Hmox, increased airway luminal occlusion. Compared with wild-type allografts, expression of inducible NO synthase (iNOS), which promotes the influx of cytoeffector leukocytes and airway graft rejection, was strikingly reduced by either enhanced expression of Hmox-1 or exogenous CO. Hmox-1/CO decreased nuclear factor (NF)-κB binding activity to the iNOS promoter region and iNOS expression. Inhibition of soluble guanylate cyclase did not interfere with the ability of CO to suppress OB, implicating a cyclic guanosine 3′,5′-monophosphate–independent mechanism through which CO suppresses NF-κB, iNOS transcription, and OB. Prolonged CO inhalation represents a new immunosuppresive strategy to prevent OB

    Ultrasound biomicroscopy findings of 25 G Transconjuctival sutureless (TSV) and conventional (20G) pars plana sclerotomy in the same patient

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    BACKGROUND: Transconjunctival Sutureless Vitrectomy (TSV) is a recent advancement in vitreo-retinal surgical techniques involving the use of 25 G instruments through self-sealing sclerotomies. It has been hypothesized that there may be less chance of vitreous and retinal herniation in the scleral wound as compared to conventional sclerotomy incision. However there are no reports on differences in 20 gauge and 25 gauge sclerotomies using ultrasound biomicroscopy (UBM). We report herein the differences in sclerotomies undertaken with 20 gauge (G) and 25 gauge instruments in the same patient. CASE PRESENTATION: Ultrasound biomicroscopy of the sclerotomy sites was done in the same patient in whom both 20 G and 25 G sclerotomies had to be constructed during pars plana vitrectomy and the differences were studied. On day 2, we observed a wide gape at the site that had been enlarged using a 20G MVR blade. In contrast, the other two sites made transconjunctivally using the 25G trocar showed only a mild gape. Significant gape continued to persist at the subsequent evaluations on day 7 and day 14 only at the port, which had been enlarged. CONCLUSION: Healing of a 25 G sclerotomy is expectedly quite rapid, with inability to detect the site of sclerotomy in a short duration of 2 weeks post-operatively. This is as opposed to conventional sclerotomies, which might take up to 6–8 weeks post-operatively for complete opposition

    Estimation of Fish Biomass Using Environmental DNA

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    Environmental DNA (eDNA) from aquatic vertebrates has recently been used to estimate the presence of a species. We hypothesized that fish release DNA into the water at a rate commensurate with their biomass. Thus, the concentration of eDNA of a target species may be used to estimate the species biomass. We developed an eDNA method to estimate the biomass of common carp (Cyprinus carpio L.) using laboratory and field experiments. In the aquarium, the concentration of eDNA changed initially, but reached an equilibrium after 6 days. Temperature had no effect on eDNA concentrations in aquaria. The concentration of eDNA was positively correlated with carp biomass in both aquaria and experimental ponds. We used this method to estimate the biomass and distribution of carp in a natural freshwater lagoon. We demonstrated that the distribution of carp eDNA concentration was explained by water temperature. Our results suggest that biomass data estimated from eDNA concentration reflects the potential distribution of common carp in the natural environment. Measuring eDNA concentration offers a non-invasive, simple, and rapid method for estimating biomass. This method could inform management plans for the conservation of ecosystems

    Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer

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    Runt domain transcription factor 3 (RUNX3) is widely regarded as a tumour-suppressor gene inactivated by DNA hypermethylation of its canonical CpG (cytidine-phosphate-guanidine) island (CGI) promoter in gastric cancer (GC). Absence of RUNX3 expression from normal gastric epithelial cells (GECs), the progenitors to GC, coupled with frequent RUNX3 overexpression in GC progression, challenge this longstanding paradigm. However, epigenetic models to better describe RUNX3 deregulation in GC have not emerged. Here, we identify lineage-specific DNA methylation at an alternate, non-CGI promoter (P1) as a new mechanism of RUNX3 epigenetic control. In normal GECs, P1 was hypermethylated and repressed, whereas in immune lineages P1 was hypomethylated and widely expressed. In human GC development, we detected aberrant P1 hypomethylation signatures associated with the early inflammatory, preneoplastic and tumour stages. Aberrant P1 hypomethylation was fully recapitulated in mouse models of gastric inflammation and tumorigenesis. Cell sorting showed that P1 hypomethylation reflects altered cell-type composition of the gastric epithelium/tumour microenvironment caused by immune cell recruitment, not methylation loss. Finally, via long-term culture of gastric tumour epithelium, we revealed that de novo methylation of the RUNX3 canonical CGI promoter is a bystander effect of oncogenic immortalization and not likely causal in GC pathogenesis as previously argued. We propose a new model of RUNX3 epigenetic control in cancer, based on immune-specific, non-CGI promoter hypomethylation. This novel epigenetic signature may have utility in early detection of GC and possibly other epithelial cancers with premalignant immune involvement
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