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https://www.readbyqxmd.com/read/29356153/mun-meristem-unstructured-encoding-a-spc24-homolog-of-ndc80-kinetochore-complex-affects-development-through-cell-division-in-arabidopsis-thaliana
#1
Jinwoo Shin, Goowon Jeong, Jong-Yoon Park, Hoyeun Kim, Ilha Lee
Kinetochore, a protein super-complex on the centromere of chromosomes, mediates chromosome segregation during cell division by providing attachment sites for spindle microtubules. The NDC80 complex, composed of four proteins, NDC80, NUF2, SPC24, and SPC25, is localized at the outer kinetochore and connects spindle fibers to the kinetochore. Although it is conserved across species, functional studies of this complex are rare in Arabidopsis. Here, we characterize a recessive mutant, meristem unstructured-1 (mun-1), exhibiting an abnormal phenotype with unstructured shoot apical meristem caused by ectopic expression of the WUSCHEL gene in unexpected tissues...
January 21, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29356147/kisspeptin-neurones-in-the-posterodorsal-medial-amygdala-modulate-sexual-partner-preference-and-anxiety-in-male-mice
#2
D A Adekunbi, X F Li, G Lass, K Shetty, O A Adegoke, S H Yeo, W H Colledge, S L Lightman, K T O'Byrne
The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is however limited information on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. This study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique...
January 22, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29355841/jak2-idh-mutant-driven-myeloproliferative-neoplasm-is-sensitive-to-combined-targeted-inhibition
#3
Anna Sophia McKenney, Allison N Lau, Amritha Varshini Hanasoge Somasundara, Barbara Spitzer, Andrew M Intlekofer, Jihae Ahn, Kaitlyn Shank, Franck T Rapaport, Minal A Patel, Efthymia Papalexi, Alan H Shih, April Chiu, Elizaveta Freinkman, Esra A Akbay, Mya Steadman, Raj Nagaraja, Katharine Yen, Julie Teruya-Feldstein, Kwok-Kin Wong, Raajit Rampal, Matthew G Vander Heiden, Craig B Thompson, Ross L Levine
Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617F and mutant IDH1R132H or Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617F Idh2R140Q-mutant MPNs were sensitive to small-molecule inhibition of IDH...
January 22, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29355678/t-cell-gene-therapy-for-perforin-deficiency-corrects-cytotoxicity-defects-and-prevents-haemophagocytic-lymphohistiocytosis-manifestations
#4
Sujal Ghosh, Marlene Carmo, Miguel Calero-Garcia, Ida Ricciardelli, Juan Carlos Bustamante Ogando, Michael P Blundell, Axel Schambach, Philip G Ashton-Rickardt, Claire Booth, Stephan Ehl, Kai Lehmberg, Adrian J Thrasher, H Bobby Gaspar
BACKGROUND: Mutations in the PRF1 gene account for up to 58% of familial haemophagocytic lymphohistiocytosis (FHL) syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinaemia and hyperactivation with inflammation in various organs. OBJECTIVE: To determine whether autologous gene corrected T cells can restore cytotoxic function, reduce disease activity and prevent haemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models. METHODS: We developed a gammaretroviral vector to transduce murine CD8-T cells in the prf-/- mouse model...
January 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29355514/a-shared-pattern-of-%C3%AE-catenin-activation-in-bronchopulmonary-dysplasia-and-idiopathic-pulmonary-fibrosis
#5
Jennifer M S Sucre, Gail H Deutsch, Christopher Jetter, Namasivayam Ambalavanan, John T Benjamin, Linda A Gleaves, Bryan A Millis, Lisa R Young, Timothy S Blackwell, Jonathan A Kropski, Susan H Guttentag
Wnt/β-catenin signaling is necessary for normal lung development, and abnormal Wnt signaling contributes to the pathogenesis of both bronchopulmonary dysplasia (BPD) and idiopathic pulmonary fibrosis (IPF), fibrotic lung diseases that occur during infancy and aging, respectively. Using a library of human normal and diseased human lung samples, we identified a distinct signature of nuclear accumulation of β-catenin phosphorylated at tyrosine 489 and epithelial cell cytosolic localization of β-catenin phosphorylated at tyrosine 654 in early normal lung development and fibrotic lung diseases BPD and IPF...
January 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29354179/the-significance-of-neonatal-thymectomy-for-shaping-the-immune-system-in-children-with-congenital-heart-defects
#6
REVIEW
Małgorzata Stosio, Jakub Ruszkowski, Anna Mikosik-Roczyńska, Ireneusz Haponiuk, Jacek M Witkowski
The thymus plays an important role in the development of the immune cell pool; it serves as the primary location for T-lymphocyte maturation. Early cardiac surgical interventions for congenital heart defects are necessarily associated with thymectomy, i.e. the partial or complete removal of the thymus. A newborn infant already has a functioning thymus and developed cells of the immune system. However, thymectomy eliminates the primary location where T cells differentiate and mature. This study summarizes the current knowledge of the cellular disturbances and potential clinical consequences associated with performing thymectomy in children treated surgically for congenital heart defects...
December 2017: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
https://www.readbyqxmd.com/read/29353885/crtc1-maml2-fusion-induced-lncrna-linc00473-expression-maintains-the-growth-and-survival-of-human-mucoepidermoid-carcinoma-cells
#7
Zirong Chen, Shuibin Lin, Jian-Liang Li, Wei Ni, Ruifeng Guo, Jianrong Lu, Frederic J Kaye, Lizi Wu
Mucoepidermoid carcinoma (MEC) arises in many glandular tissues and contributes to the most common malignant salivary gland cancers. MEC is specifically associated with a unique t(11;19) translocation and the resulting CRTC1-MAML2 fusion is a major oncogenic driver for MEC initiation and maintenance. However, the molecular basis underlying the CRTC1-MAML2 oncogenic functions remains elusive. Through gene expression profiling analysis, we observed that LINC00473, a long non-coding RNA (lncRNA), was the top down-regulated target in CRTC1-MAML2-depleted human MEC cells...
January 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29353404/dna-methylation-rather-than-single-nucleotide-polymorphisms-regulates-the-production-of-an-aberrant-splice-variant-of-il6r-in-mastitic-cows
#8
Yan Zhang, Xiuge Wang, Qiang Jiang, Haisheng Hao, Zhihua Ju, Chunhong Yang, Yan Sun, Changfa Wang, Jifeng Zhong, Jinming Huang, Huabin Zhu
Interleukin-6 receptor-alpha (IL6R) interacts with IL6 and forms a ligand-receptor complex, which can stimulate various cellular responses, such as cell proliferation, cell differentiation, and activation of inflammatory processes. Both genetic mutation and epigenetic modification regulate gene transcription. We identified a novel splice variant of bovine IL6R, designated as IL6R-TV, which is characterized by the skipping of exon 2 of the NCBI-referenced IL6R gene (IL6R-reference). The expression levels of IL6R-TV and IL6R-reference transcripts were lower in normal mammary gland tissues...
January 20, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29353075/btla-marks-a-less-cytotoxic-t-cell-subset-in-diffuse-large-b-cell-lymphoma-with-high-expression-of-checkpoints
#9
Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu
Immunotherapy has shown encouraging results in lymphoma. Pre-clinical and clinical trials have proven checkpoint blockade, such as PD-1 antibody, as an effective treatment for lymphoma, including diffuse large B-cell lymphoma (DLBCL). Combination of checkpoint blockades has emerged as a new way to treat lymphoma, however, the status of checkpoints expression and their function in DLBCL has not been fully elucidated yet. In this study, we examined the expression of BTLA, PD-1, TIM-3, LIGHT and LAG-3 in tumor micro-environmental T cells of DLBCL using flow cytometry, and compared the cytotoxicity and differentiation status of BTLA+ and BTLA- T-cells...
January 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29353058/chd7-is-critical-for-early-t-cell-development-and-thymus-organogenesis-in-zebrafish
#10
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353010/modulation-of-immune-responses-by-plasmodium-falciparum-infection-in-asymptomatic-children-living-in-the-endemic-region-of-mbita-western-kenya
#11
Caroline Kijogi, Daisuke Kimura, Lam Quoc Bao, Risa Nakamura, Evans Asena Chadeka, Ngetich Benard Cheruiyot, Felix Bahati, Kazuhide Yahata, Osamu Kaneko, Sammy M Njenga, Yoshio Ichinose, Shinjiro Hamano, Katsuyuki Yui
Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4-16years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya...
January 15, 2018: Parasitology International
https://www.readbyqxmd.com/read/29352860/towards-targeting-resolution-pathways-of-airway-inflammation-in-asthma
#12
REVIEW
Cindy Barnig, Nelly Frossard, Bruce D Levy
Asthma is a chronic disorder characterized by persistent inflammation of the airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells, and release of proinflammatory cytokines and lipid mediators. The natural resolution of airway inflammation is now recognized as an active host response, with highly coordinated cellular events under the control of endogenous pro-resolving mediators that enable the restoration of tissue homeostasis. Lead members of proresolving mediators are enzymatically derived from essential polyunsaturated fatty acids, including arachidonic acid-derived lipoxins, eicosapentaenoic acid-derived E-series resolvins, and docosahexaenoic acid-derived D-series resolvins, protectins, and maresins...
January 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29352747/clathrin-and-ap1-are-required-for-apical-sorting-of-gpi-aps-in-biosynthetic-and-recycling-routes-in-mdck-cells
#13
Guillaume Alain Castillon, Patricia Burriat-Couleru, Daniel Abegg, Nina Criado Santos, Reika Watanabe
Recently studies in animal models demonstrate potential roles for clathrin and AP1 in apical protein sorting in epithelial tissue. However, the precise functions of these proteins in apical protein transport remain unclear. Here, we reveal mis-targeting of endogenous GPI-APs and soluble secretory proteins in MDCK cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a novel directional endocytosis and recycling assay, we found that these KD cells are not only affected for apical sorting of GPI-APs in biosynthetic pathway but also for their apical recycling and basal to apical transcytosis routes...
January 20, 2018: Traffic
https://www.readbyqxmd.com/read/29352448/mesenchymal-stem-cell-deformability-and-implications-for-microvascular-sequestration
#14
Herbert H Lipowsky, Daniel T Bowers, Britany L Banik, Justin L Brown
Mesenchymal stem cells (MSCs) have received considerable attention in regenerative medicine, particularly in light of prospects for targeted delivery by intra-arterial injection. However, little is known about the mechanics of MSC sequestration in the microvasculature and the yield pressure (PY), above which MSCs will pass through microvessels of a given diameter. The objectives of the current study were to delineate the dependency of PY on cell size and the heterogeneity of cell mechanical properties and diameters (DCELL) of cultured MSCs...
January 19, 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29352298/hexokinase-ii-may-be-dispensable-for-cd4-t-cell-responses-against-a-virus-infection
#15
Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T Rouse
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#16
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352287/ifn%C3%AE-inhibits-g-csf-induced-neutrophil-expansion-and-invasion-of-the-cns-to-prevent-viral-encephalitis
#17
Chandran Ramakrishna, Edouard M Cantin
Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352190/autophagy-promotes-msc-mediated-vascularization-in-cutaneous-wound-healing-via-regulation-of-vegf-secretion
#18
Y An, W J Liu, P Xue, Y Ma, L Q Zhang, B Zhu, M Qi, L Y Li, Y J Zhang, Q T Wang, Y Jin
Vascularization deficiency caused a lot of diseases, such as diabetes ulcer and myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and multipotent differentiation capacities, have been used for many diseases treatment through regulation microenvironment. Numerous studies reported that MSCs transplantation could largely improve cutaneous wound healing via paracrine secretion of growth factors. However, whether MSCs take part in the angiogenesis process directly remains elusive. Previous study proved that autophagy inhibited immunosuppressive function of MSCs and prevented the degradation of MSCs function in inflammatory and senescent microenvironment...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352186/glycolysis-promotes-caspase-3-activation-in-lipid-rafts-in-t-cells
#19
Michael A Secinaro, Karen A Fortner, Oliver Dienz, Angela Logan, Michael P Murphy, Vikas Anathy, Jonathan E Boyson, Ralph C Budd
Resting T cells undergo a rapid metabolic shift to glycolysis upon activation in the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial respiration with IL-15. Paralleling these different metabolic states are striking differences in susceptibility to restimulation-induced cell death (RICD); glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic T cells are resistant. It is unclear whether the metabolic state of a T cell is linked to its susceptibility to RICD. Our findings reveal that IL-2-driven glycolysis promotes caspase-3 activity and increases sensitivity to RICD...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352109/role-of-b-and-t-lymphocyte-attenuator-in-renal-transplant-recipients-with-biopsy-proven-acute-rejection
#20
Zijie Wang, Haiwei Yang, Xuzhong Liu, Jingying Zhang, Zhijian Han, Jun Tao, Chunchun Zhao, Xiaobin Ju, Ruoyun Tan, Min Gu
BACKGROUND Acute rejection is a common predisposing cause of allograft dysfunction in kidney transplantation. Recently, the B and T lymphocyte attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160 pathway was found to be potentially involved in the regulation of T cell activation. This could mean that this pathway is involved in graft rejection in kidney transplantation; the present study aimed to explore this possibility. MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients with biopsy-proven acute rejection (BPAR) or stable allograft function, as well as in healthy volunteers...
January 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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