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Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
March 5, 2018: Autoimmunity
Lai Wei, Xuan Zhang, Zhihai Zhang, Huanhuan Liu, Zhongwei Lin
The applications of semi-dwarf genes such as sd1 and Rht1 in rice and wheat resulted in the first "green revolution" in the 1960s. However, such semi-dwarf genes that can efficiently reduce plant stature and have few negative yield traits have not yet been identified in maize. In this study, a new allele of Brachytic2 gene (qpa1) encoding P-glycoprotein was rapidly fine-mapped using a modified method. The qpa1, containing a 241-bp deletion in the last exon, had no negative effect on yield, but greatly modified the plant architecture including significantly reduced plant height and ear height, increased stalk diameter and erected leaf...
February 23, 2018: Heredity
Ning Yuan, Shuangrong Yuan, Zhigang Li, Man Zhou, Peipei Wu, Qian Hu, Liangjiang Wang, Venugopal Mendu, Hong Luo
Protein kinases play fundamental roles in plant development and environmental stress responses. Here, we identified the STRESS INDUCED FACTOR (SIF) gene family, which encodes four leucine-rich repeat receptor-like protein kinases (LRR-RLKs) in Arabidopsis thaliana. The four genes, SIF1-4, are clustered in the genome and highly conserved, but have temporally and spatially distinct expression patterns. We employed Arabidopsis SIF knockout mutants and overexpression transgenics to examine SIF involvement during plant pathogen defense...
February 20, 2018: Plant Physiology
Svenja Memmert, A V B Nogueira, A Damanaki, M Nokhbehsaim, S Eick, T Divnic-Resnik, A Spahr, B Rath-Deschner, A Till, W Götz, J A Cirelli, A Jäger, J Deschner
OBJECTIVES: Damage-regulated autophagy modulator (DRAM) 1 is a p53 target gene with possible involvement in oral inflammation and infection. This study sought to examine the presence and regulation of DRAM1 in periodontal diseases. MATERIAL AND METHODS: In vitro, human periodontal ligament fibroblasts were exposed to interleukin (IL)-1β and Fusobacterium nucleatum for up to 2 days. The DRAM1 synthesis and its regulation were analyzed by real-time PCR, immunocytochemistry, and ELISA...
February 13, 2018: Clinical Oral Investigations
Yan Wang, Yuanpeng Xu, Yujing Sun, Huibin Wang, Jiaming Qi, Bowen Wan, Wenwu Ye, Yachun Lin, Yuanyuan Shao, Suomeng Dong, Brett M Tyler, Yuanchao Wang
Activation of innate immunity by membrane-localized receptors is conserved across eukaryotes. Plant genomes contain hundreds of such receptor-like genes and those encoding proteins with an extracellular leucine-rich repeat (LRR) domain represent the largest family. Here, we develop a high-throughput approach to study LRR receptor-like genes on a genome-wide scale. In total, 257 tobacco rattle virus-based constructs are generated to target 386 of the 403 identified LRR receptor-like genes in Nicotiana benthamiana for silencing...
February 9, 2018: Nature Communications
Chunwan Lu, Dafeng Yang, Maria E Sabbatini, Aaron H Colby, Mark W Grinstaff, Nicholas H Oberlies, Cedric Pearce, Kebin Liu
BACKGROUND: Pancreas ductal adenocarcinoma (PDAC) has the most dismal prognosis among all human cancers since it is highly resistant to chemotherapy, radiotherapy and immunotherapy. The anticipated consequence of all therapies is induction of tumor apoptosis. The highly resistance nature of PDACs to all therapies suggests that the intrinsic tumor cell factors, likely the deregulated apoptosis pathway, are key mechanisms underlying PDAC non-response to these therapies, rather than the therapeutic agents themselves...
February 6, 2018: BMC Cancer
Joy M Johnson, Johannes Thürich, Elena Kristin Petutschnig, Lothar Altschmied, Doreen Meichsner, Irena Sherameti, Julian Dindas, Anna Mrozinska, Christian Paetz, Sandra S Scholz, Alexandra Cu Furch, Volker Lipka, Rainer Hedrich, Bernd Schneider, Aleš Svatoš, Ralf Oelmüller
Piriformospora indica, an endophytic root-colonizing fungus, efficiently promotes plant growth and induces resistance to abiotic stress and biotic diseases. The fungal cell wall extract induces cytoplasmic calcium [Ca2+]cyt elevation in host plant roots. Here, we show that an elici-tor-active cell wall moiety, released by P. indica into the medium, is cellotriose (CT). CT in-duces a mild defense-like response including the production of reactive oxygen species, changes in membrane potentials and the expression of genes involved in growth regulation and root development...
January 25, 2018: Plant Physiology
Santiago Lima, Kazuaki Takabe, Jason Newton, Kumar Saurabh, Megan M Young, Andreia Machado Leopoldino, Nitai C Hait, Jane L Roberts, Hong-Gang Wang, Paul Dent, Sheldon Milstien, Laurence Booth, Sarah Spiegel
The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arrest, apoptosis, and macroautophagy/autophagy. However, little is still known of the relationship between TP53 and SPHK1 activity in the regulation of these processes. To explore this link, we examined the effects of inhibiting SPHK1 in wild-type and TP53 null cancer cell lines...
January 25, 2018: Autophagy
Eun-Seok Oh, Yeon Lee, Won Byoung Chae, Jana Jeevan Rameneni, Yong-Soon Park, Yong Pyo Lim, Man-Ho Oh
Protein post-translational modification by phosphorylation is essential for the activity and stability of proteins in higher plants and underlies their responses to diverse stimuli. There are more than 300 leucine-rich repeat receptor-like kinases (LRR-RLKs), a major group of receptor-like kinases (RLKs) that plays an important role in growth, development, and biotic stress responses in higher plants. To analyze auto- and transphosphorylation patterns and kinase activities in vitro, 43 full-length complementary DNA (cDNA) sequences were cloned from genes encoding LRR-RLKs...
January 22, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ping Liu, Feng Chang, Ting Zhang, Gang Gao, Chen Yu, Sheng-Qiang Ding, Gen-Le Zuo, Xin-Hu Huang
Objectives: To investigate the role of the microRNA-125a (miR-125a) and BAK1 in intervertebral disc degeneration (IDD). Materials and Methods: Degenerative lumbar nucleus pulposus (NP) tissues were obtained from 193 patients who underwent resection, and normal controls consisted of normal NP tissues from 32 patients with traumatic lumbar fracture in our hospital. All patients were graded according to the Pfirrmann criteria. QRT-PCR was used to detect the expression of miR-125a and BAK1, and apoptosis of NP tissues detected by TUNEL staining...
November 2017: Iranian Journal of Basic Medical Sciences
Toshihiko Tanno, Peng Zhang, Christopher A Lazarski, Yang Liu, Pan Zheng
The efficacy of traditional chemotherapy is limited by its toxicity, especially with regard to hematopoiesis. Here we show that miR-26a plays a critical role in protecting mice against chemotherapy-induced myeloid suppression by targeting a proapoptotic protein (Bak1) in hematopoietic stem/progenitor cells (HSPCs). Because c-Kit is expressed at high levels in HSPCs, we designed a microRNA-aptamer chimera that contains miR-26a mimic and c-Kit-targeting aptamer and successfully delivered miR-26a into HSPCs to attenuate toxicity of 5' fluorouracil (5-FU) and carboplatin...
June 27, 2017: Blood Advances
Qinsong Liu, Thomas Vain, Corrado Viotti, Siamsa M Doyle, Danuše Tarkowská, Ondřej Novák, Cyril Zipfel, Folke Sitbon, Stéphanie Robert, Daniel Hofius
Brassinosteroid (BR) hormone signaling controls multiple processes during plant growth and development and is initiated at the plasma membrane through the receptor kinase BRASSINOSTEROID INSENSITIVE1 (BRI1) together with co-receptors such as BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1). BRI1 abundance is regulated by endosomal recycling and vacuolar targeting, but the role of vacuole-related proteins in BR receptor dynamics and BR responses remain elusive. Here, we show that the absence of two DUF300 domain-containing tonoplast proteins, LAZARUS1 (LAZ1) and LAZ1 HOMOLOG1 (LAZ1H1), causes vacuole morphology defects, growth inhibition, and constitutive activation of BR signaling...
December 27, 2017: Molecular Plant
Liz Mariely Garcia-Peterson, Mary Ann Ndiaye, Chandra K Singh, Gagan Chhabra, Wei Huang, Nihal Ahmad
Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant SIRT6 mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant SIRT6 overexpression in human melanoma tissues...
September 2017: Genes & Cancer
Xiayun Yang, Shusheng Tang, Daowen Li, Xiaohong Yu, Fuyun Wang, Xilong Xiao
Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway...
June 2018: Journal of Cellular Physiology
Alexander S Moffett, Kyle W Bender, Steven C Huber, Diwakar Shukla
Growing evidence supports the importance of protein S-glutathionylation as a regulatory post-translational modification with functional consequences for proteins. Discoveries of redox-state-dependent protein kinase S-glutathionylation have fueled discussion of redox-sensitive signaling. Following previously published experimental evidence for S-glutathionylation induced deactivation of the Arabidopsis thaliana kinase BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1), we investigated the consequences of S-glutathionylation on the equilibrium conformational ensemble of BAK1 using all-atom molecular dynamics simulations...
December 5, 2017: Biophysical Journal
W S Xin, F Zhang, G R Yan, W W Xu, S J Xiao, Z Y Zhang, L S Huang
A large proportion of gilts and sows are culled from reproduction populations because of anestrus and pubertal reproductive failure. Selecting early onset of puberty gilts has a favorable effect on sows' reproductivity. However, age at puberty is hard to be routinely measured in commercial herds. With molecular genetic predictors, identifying individuals that have a propensity for early onset of puberty can be simplified. We previously performed genome scanning and a genome-wide association study for puberty in an F2 resource population using 183 microsatellites and 62 125 SNPs respectively...
February 2018: Animal Genetics
Hyunggon Mang, Baomin Feng, Zhangjian Hu, Aurélien Boisson-Dernier, Christina M Franck, Xiangzong Meng, Yanyan Huang, Jinggeng Zhou, Guangyuan Xu, Taotao Wang, Libo Shan, Ping He
Plants have evolved two tiers of immune receptors to detect infections: cell surface-resident pattern recognition receptors (PRRs) that sense microbial signatures and intracellular nucleotide binding domain leucine-rich repeat (NLR) proteins that recognize pathogen effectors. How PRRs and NLRs interconnect and activate the specific and overlapping plant immune responses remains elusive. A genetic screen for components controlling plant immunity identified ANXUR1 (ANX1), a malectin-like domain-containing receptor-like kinase, together with its homolog ANX2, as important negative regulators of both PRR- and NLR-mediated immunity in Arabidopsis thaliana ANX1 constitutively associates with the bacterial flagellin receptor FLAGELLIN-SENSING2 (FLS2) and its coreceptor BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1)...
December 2017: Plant Cell
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisicak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and previous we have shown that these two effectors are also needed for mitochondrial-dependent cellular necrosis (Karch et al., 2013). Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
Weiping Wang, Rong Wang, Qiao Zhang, Gil Mor, Huidong Zhang
Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) is an endocrine disrupter and ultimate carcinogenic product of benzo(a)pyrene (BaP). Numerous studies have shown that BPDE causes trophoblast-related diseases, such as preeclampsia, growth restriction or miscarriages. However, the underlying mechanism, especially the mitochondria-related BPDE-induced trophoblast dysfunction remains unknown. In this study, we examined mitochondrial functions in BPDE-induced human trophoblast cell line Swan 71. BPDE decreased cell ability, attenuated cell invasion and HCG secretion, induced cell apoptosis, decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) and MDA, and decreased SOD activity in a dose-dependent manner...
November 13, 2017: Environmental Pollution
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