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关键词： Primary ciliogenesis   Cilia length   Cobalt chloride   Hypoxia   Rabaptin-5   Endocytosis  

摘要： Primary cilia are microtubule-based organelles that are involved in sensing micro-environmental cues and regulating cellular homeostasis via triggering signaling cascades. Hypoxia is one of the most common environmental stresses that organ and tissue cells may often encounter during embryogenesis, cell differentiation, infection, inflammation, injury, cerebral and cardiac ischemia, or tumorigenesis. Although hypoxia has been reported to promote or inhibit primary ciliogenesis in different tissues or cultured cell lines, the role of hypoxia in ciliogenesis is controversial and still unclear. Here we investigated the primary cilia change under cobalt chloride (CoCl2)-simulated hypoxia in immortalized human retina pigment epithelial-1 (hTERT RPE-1) cells. We found CoCl2 treatment elongated primary cilia in a time- and dose-dependent manner. The prolonged cilia recovered back to near normal length when CoCl2 was washed out from the cell culture medium. Under CoCl2-simulated hypoxia, the protein expression levels of HIF-1/2 alpha and acetylated-alpha-tubulin (cilia marker) were increased, while the protein expression level of Rabaptin-5 is decreased during hypoxia. Taken together, our results suggest that hypoxia may elongate primary cilia by downregulating Rabaptin-5 involved endocytosis. The coordination between endocytosis and ciliogenesis may be utilized by cells to adapt to hypoxia. (C) 2021 Elsevier Inc. All rights reserved.

关键词： chief cell   gastric adenocarcinoma of fundic gland (chief cell predominant type)   mucin-6   pepsinogen-I   tubular adenocarcinoma  

摘要： Rationale: Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers. Patient concerns: An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion. Interventions: We performed endoscopic submucosal dissection, and successfully removed the lesion. Diagnosis: Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP. Outcomes: The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months). Lessons: We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.

关键词： Mechanisms of disease   Osteoarthritis  

摘要： Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.

关键词： gene expression   inflammation   b-lymphocytes   biopsy   cholangitis   colorectal cancer   inflammatory bowel disease   ulcerative colitis   fibroblasts   bile ducts   sclerosing cholangitis   colitis   collagenase   cryopreservation   digestion   enterocytes   genes   genomics   intestinal diseases   intestines   libraries   plasma cells   sequence analysis   rna   immunoglobulin a   colon   mucous membrane   stress   inflammatory disorders   causality  

摘要： Background Primary sclerosing cholangitis (PSC) is an inflammatory disorder of the bile ducts. The etiology of PSC is unknown, but it is hypothesized that intestinal barrier dysfunction, as seen in inflammatory bowel disease (IBD), plays a role. Roughly 75% of PSC patients have concomitant IBD (PSC-IBD). PSC-IBD is phenotypically different from ulcerative colitis (UC) with predominantly right-sided disease and a higher risk for colorectal cancer. In this study we aim aim to find probable distinct pathomechanisms for PSC-IBD, by comparing gut mucosal biopsies between PSC-IBD and UC using single-cell RNA *** 47 gut mucosal samples from the colon of subjects with either PSC-IBD (n=24), UC (n=18) or non-IBD control (n=5) were collected, from which 28 were paired inflamed and non-inflamed. Whole biopsies were cryopreserved and dissociated into single cells using collagenase digestion. Library preparation was done using the 10x Genomics system and subsequent sequencing was performed on an MGI2000 sequencer. The ‘Seurat’ R package was used for *** A total of 75.078 high quality cells identified 38 distinct cell types. No differences in cell type composition were observed between PSC-IBD and UC. We did see different cell type composition and gene expression between inflamed and non-inflamed samples. For example, in PSC-IBD specifically, an enterocyte subtype defined by DUOX2-expression showed inflammatory pathways upon inflammation. UC inflammation, on the other hand, was characterized by involvement of BEST4+ enterocytes and inflammatory fibroblasts. In addition, activated B cells and IgA plasma cells expressed stress-related genes in PSC, but not in UC *** We show that intestinal inflammation in PSC-IBD is characterized by distinct, cell-specific gene expression patterns as compared to UC. This highlights differential cell types mediating inflammation between these IBDs. Our study provides insight in cellular mechanisms unde

关键词： connectivity   emotion   inhibitory cells   interneuron   local circuits   neuropeptide  

摘要： GABAergic neurons are key circuit elements in cortical networks. Despite growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types has been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22%) is significantly higher than in the LA (16%) in both male and female mice. No difference was observed between the right and left hemispheres in either sex. In addition, we assessed the ratio of the major inhibitory cell types in both amygdalar nuclei. Using transgenic mice and a viral strategy for visualizing inhibitory cells combined with immunocytochemistry, we estimated that the following cell types together compose the vast majority of GABAergic cells in the LA and BA: axo-axonic cells (5.5%-6%), basket cells expressing parvalbumin (17%-20%) or cholecystokinin (7%-9%), dendrite-targeting inhibitory cells expressing somatostatin (10%-16%), NPY-containing neurogliaform cells (14%-15%), VIP and/or calretinin-expressing interneuron-selective interneurons (29%-38%), and GABAergic projection neurons expressing somatostatin and neuronal nitric oxide synthase (5.5%-8%). Our results show that these amygdalar nuclei contain all major GABAergic neuron types as found in other cortical regions. Furthermore, our data offer an essential reference for future studies aiming to reveal changes in GABAergic cell number and in inhibitory cell types typically observed under different pathologic conditions, and to model functioning amygdalar networks in health and disease.

摘要： Food is the basic needs of our daily life. In urban dense cities, the space to grow food becomes too scarce. The problem is the food consumption per household globally is getting high on numbers. In the Netherlands, the average households have a high ecological footprint on food consuming, which is the twice of the world average. Companies like Bowery are distributing annually tons of vertical farmed vegetables throughout the whole world. But the transport costs are high and it produces a lot of waste and air pollution. Food waste and transportation are the factors that causes the big impact on the way we are consuming food and the environment. Food production can help to reduce these high rates. It can be reduced by starting producing food locally that uses less transport costs. This thesis proposes a residential tower scheme, which can be seen as an alternative for vertical farming in urban dense cities, and contains different variations in outdoor growing balconies for producing food for daily life. By distributing to the nearby neigh- bourhood, it can benefit from fresh food. The spatial quality of these balconies can be defined as the main feature in this building, to grow, to share and to harvest the food. The STEM-tower, recognized by the natural form of a tree stem, housing four types of apartments: the lofts are differentiated in S, M, L, XL, are gradually ranged from low to high, which is categorized to house the different classes of households. The outdoor balconies are the central growing space in the apartment where the residents can grow, harvest & store their crops. The types of vegetation can be differ- entiating by sun orientation and height. The special vegetation units are growing crops indoor, which can be entered by the residents themselves and the service gardeners. They have access to all the vegetation units and the outdoor growing spaces on each floor. Space for growing food in urbanized cities becomes scarce in plot size. The outdoor vegeta