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Miriam Ratliff, Katherine L Hill-Harfe, Elizabeth J Gleason, Huiping Ling, Tim L Kroft, Steven W L'Hernault
Covalent attachment of ubiquitin to substrate proteins changes their function or marks them for proteolysis, and specificity of ubiquitin attachment is mediated by the numerous E3 ligases encoded by animals. Mind Bomb is an essential E3 ligase during Notch pathway signaling in insects and vertebrates. While C. elegans encodes a Mind Bomb homolog ( mib-1 ), it has never been recovered in the extensive Notch suppressor/enhancer screens that have identified numerous pathway components. Here, we show that C. elegans mib-1 null mutants have a spermatogenesis-defective phenotype that results in a heterogeneous mixture of arrested spermatocytes, defective spermatids and motility-impaired spermatozoa...
March 12, 2018: Genetics
Marie McGovern, Perla Gisela Castaneda, Olga Pekar, Laura G Vallier, Erin J Cram, E Jane Albert Hubbard
DSL ligands activate the Notch receptor in many cellular contexts across metazoa to specify cell fate. In addition, Notch receptor activity is implicated in post-mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it can act as a latent proliferation-promoting signal to maintain proximal germline tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the maintenance of normal ovulation...
January 22, 2018: Developmental Biology
Andrea Barbieri, Silvia Carra, Pasquale De Blasio, Franco Cotelli, Ida Biunno
SEL1L (suppressor/enhancer of Lin-12-like) is a highly conserved gene associated with the endoplasmic reticulum-associated degradation (ERAD) pathway and involved in mediating the balance between stem cells self-renewal and differentiation of neural progenitors. It has been recently shown that SEL1L KO mice are embryonic lethal and display altered organogenesis. To better characterize the function of SEL1L in the early stages of embryonic development, we turned to the zebrafish model (Danio rerio). After exploring sel1l expression by RT-PCR and in situ hybridization, we employed a morpholino-mediated down-regulation approach...
December 7, 2017: Journal of Cellular Physiology
Qinfang Shen, Leila B Toulabi, Herong Shi, Erin E Nicklow, Jun Liu
The proper development of a multicellular organism requires precise spatial and temporal coordination of cell intrinsic and cell extrinsic regulatory mechanisms. Both Notch signaling and bone morphogenetic protein (BMP) signaling function to regulate the proper development of the C. elegans postembryonic mesoderm. We have identified the C. elegans FOXD transcription factor UNC-130 as a major target functioning downstream of both BMP signaling and Notch signaling to regulate dorsoventral patterning of the postembryonic mesoderm...
January 1, 2018: Developmental Biology
Ryan S Underwood, Yuting Deng, Iva Greenwald
Six initially equivalent, multipotential Vulval Precursor Cells (VPCs) in Caenorhabditis elegans adopt distinct cell fates in a precise spatial pattern, with each fate associated with transcription of different target genes. The pattern is centered on a cell that adopts the "1°" fate through Epidermal Growth Factor Receptor (EGFR) activity, and produces a lateral signal composed of ligands that activate LIN-12/Notch in the two flanking VPCs to cause them to adopt "2°" fate. Here, we investigate orthologs of a transcription complex that acts in mammalian EGFR signaling- lin-1 /Elk1, sur-2/ Med23, and the Cdk8 Kinase module (CKM)-previously implicated in aspects of 1° fate in C...
December 2017: Genetics
Yuting Deng, Iva Greenwald
Upon ligand binding, the LIN-12/Notch intracellular domain is released from its transmembrane tether to function in a nuclear complex to activate transcription of target genes. During Caenorhabditis elegans vulval development, LIN-12/Notch is activated by ligand in two of six multipotential Vulval Precursor Cells (VPCs), specifying the "2o vulval fate" and descendants that contribute to the vulva. If LIN-12 is ectopically activated in other VPCs, they also adopt the 2o fate, dividing to produce extra vulval cells and resulting in a "Multivulva" phenotype...
September 19, 2016: G3: Genes—Genomes—Genetics
Yvonne C Lussi, Luca Mariani, Carsten Friis, Juhani Peltonen, Toshia R Myers, Claudia Krag, Garry Wong, Anna Elisabetta Salcini
Methylation of histone 3 lysine 4 (H3K4) is largely associated with promoters and enhancers of actively transcribed genes and is finely regulated during development by the action of histone methyltransferases and demethylases. H3K4me3 demethylases of the KDM5 family have been previously implicated in development, but how the regulation of H3K4me3 level controls developmental processes is not fully established. Here, we show that the H3K4 demethylase RBR-2, the unique member of the KDM5 family in C. elegans, acts cell-autonomously and in a catalytic-dependent manner to control vulva precursor cells fate acquisition, by promoting the LIN-12/Notch pathway...
October 15, 2016: Development
Komal Safdar, Anniya Gu, Xia Xu, Vinci Au, Jon Taylor, Stephane Flibotte, Donald G Moerman, Eleanor M Maine
Notch-type signaling mediates cell-cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell-cell interactions during larval development...
July 7, 2016: G3: Genes—Genomes—Genetics
Alparsan Asan, Stephan A Raiders, James R Priess
Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development...
April 2016: PLoS Genetics
Norihiro Kato, Marie Loh, Fumihiko Takeuchi, Niek Verweij, Xu Wang, Weihua Zhang, Tanika N Kelly, Danish Saleheen, Benjamin Lehne, Irene Mateo Leach, Alexander W Drong, James Abbott, Simone Wahl, Sian-Tsung Tan, William R Scott, Gianluca Campanella, Marc Chadeau-Hyam, Uzma Afzal, Tarunveer S Ahluwalia, Marc Jan Bonder, Peng Chen, Abbas Dehghan, Todd L Edwards, Tõnu Esko, Min Jin Go, Sarah E Harris, Jaana Hartiala, Silva Kasela, Anuradhani Kasturiratne, Chiea-Chuen Khor, Marcus E Kleber, Huaixing Li, Zuan Yu Mok, Masahiro Nakatochi, Nur Sabrina Sapari, Richa Saxena, Alexandre F R Stewart, Lisette Stolk, Yasuharu Tabara, Ai Ling Teh, Ying Wu, Jer-Yuarn Wu, Yi Zhang, Imke Aits, Alexessander Da Silva Couto Alves, Shikta Das, Rajkumar Dorajoo, Jemma C Hopewell, Yun Kyoung Kim, Robert W Koivula, Jian'an Luan, Leo-Pekka Lyytikäinen, Quang N Nguyen, Mark A Pereira, Iris Postmus, Olli T Raitakari, Molly Scannell Bryan, Robert A Scott, Rossella Sorice, Vinicius Tragante, Michela Traglia, Jon White, Ken Yamamoto, Yonghong Zhang, Linda S Adair, Alauddin Ahmed, Koichi Akiyama, Rasheed Asif, Tin Aung, Inês Barroso, Andrew Bjonnes, Timothy R Braun, Hui Cai, Li-Ching Chang, Chien-Hsiun Chen, Ching-Yu Cheng, Yap-Seng Chong, Rory Collins, Regina Courtney, Gail Davies, Graciela Delgado, Loi D Do, Pieter A Doevendans, Ron T Gansevoort, Yu-Tang Gao, Tanja B Grammer, Niels Grarup, Jagvir Grewal, Dongfeng Gu, Gurpreet S Wander, Anna-Liisa Hartikainen, Stanley L Hazen, Jing He, Chew-Kiat Heng, James E Hixson, Albert Hofman, Chris Hsu, Wei Huang, Lise L N Husemoen, Joo-Yeon Hwang, Sahoko Ichihara, Michiya Igase, Masato Isono, Johanne M Justesen, Tomohiro Katsuya, Muhammad G Kibriya, Young Jin Kim, Miyako Kishimoto, Woon-Puay Koh, Katsuhiko Kohara, Meena Kumari, Kenneth Kwek, Nanette R Lee, Jeannette Lee, Jiemin Liao, Wolfgang Lieb, David C M Liewald, Tatsuaki Matsubara, Yumi Matsushita, Thomas Meitinger, Evelin Mihailov, Lili Milani, Rebecca Mills, Nina Mononen, Martina Müller-Nurasyid, Toru Nabika, Eitaro Nakashima, Hong Kiat Ng, Kjell Nikus, Teresa Nutile, Takayoshi Ohkubo, Keizo Ohnaka, Sarah Parish, Lavinia Paternoster, Hao Peng, Annette Peters, Son T Pham, Mohitha J Pinidiyapathirage, Mahfuzar Rahman, Hiromi Rakugi, Olov Rolandsson, Michelle Ann Rozario, Daniela Ruggiero, Cinzia F Sala, Ralhan Sarju, Kazuro Shimokawa, Harold Snieder, Thomas Sparsø, Wilko Spiering, John M Starr, David J Stott, Daniel O Stram, Takao Sugiyama, Silke Szymczak, W H Wilson Tang, Lin Tong, Stella Trompet, Väinö Turjanmaa, Hirotsugu Ueshima, André G Uitterlinden, Satoshi Umemura, Marja Vaarasmaki, Rob M van Dam, Wiek H van Gilst, Dirk J van Veldhuisen, Jorma S Viikari, Melanie Waldenberger, Yiqin Wang, Aili Wang, Rory Wilson, Tien-Yin Wong, Yong-Bing Xiang, Shuhei Yamaguchi, Xingwang Ye, Robin D Young, Terri L Young, Jian-Min Yuan, Xueya Zhou, Folkert W Asselbergs, Marina Ciullo, Robert Clarke, Panos Deloukas, Andre Franke, Paul W Franks, Steve Franks, Yechiel Friedlander, Myron D Gross, Zhirong Guo, Torben Hansen, Marjo-Riitta Jarvelin, Torben Jørgensen, J Wouter Jukema, Mika Kähönen, Hiroshi Kajio, Mika Kivimaki, Jong-Young Lee, Terho Lehtimäki, Allan Linneberg, Tetsuro Miki, Oluf Pedersen, Nilesh J Samani, Thorkild I A Sørensen, Ryoichi Takayanagi, Daniela Toniolo, Habibul Ahsan, Hooman Allayee, Yuan-Tsong Chen, John Danesh, Ian J Deary, Oscar H Franco, Lude Franke, Bastiaan T Heijman, Joanna D Holbrook, Aaron Isaacs, Bong-Jo Kim, Xu Lin, Jianjun Liu, Winfried März, Andres Metspalu, Karen L Mohlke, Dharambir K Sanghera, Xiao-Ou Shu, Joyce B J van Meurs, Eranga Vithana, Ananda R Wickremasinghe, Cisca Wijmenga, Bruce H W Wolffenbuttel, Mitsuhiro Yokota, Wei Zheng, Dingliang Zhu, Paolo Vineis, Soterios A Kyrtopoulos, Jos C S Kleinjans, Mark I McCarthy, Richie Soong, Christian Gieger, James Scott, Yik-Ying Teo, Jiang He, Paul Elliott, E Shyong Tai, Pim van der Harst, Jaspal S Kooner, John C Chambers
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure...
November 2015: Nature Genetics
Kai-Biao Lin, K Robert Lai, Nan-Ping Yang, Chien-Lung Chan, Yuan-Hung Liu, Ren-Hao Pan, Chien-Hsun Huang
INTRODUCTION: This paper presents an epidemiologic study of appendicitis in Taiwan over a twelve-year period. An analysis of the incidence in the low-income population (LIP) is included to explore the effects of lower socioeconomic status on appendicitis. METHODS: We analyzed the epidemiological features of appendicitis in Taiwan using data from the National Health Insurance Research Database (NHIRD) from 2000 to 2011. All cases diagnosed as appendicitis were enrolled...
2015: World Journal of Emergency Surgery: WJES
Li Jiang, Zu-Lin Dou, Qing Wang, Qiao-Yuan Wang, Meng Dai, Zhen Wang, Xiao-Mei Wei, Ying-Bei Chen
OBJECTIVE: Using ultrasonography (US) to guide botulinum toxin type A (BTX-A) injection in patients with post-stroke wrist and finger flexor muscle spasticity and assessing clinical outcomes after the injection and rehabilitation intervention. METHODS: Twenty-three patients with wrist and finger spasticity after stroke were recruited in this study from May 2012 to May 2013. Under US guidance, the proper dose (250 U) of BTX-A was injected into each spastic muscle at two injection sites...
2015: Frontiers in Human Neuroscience
Benjamin Liang, Jen Ming Lai, Arul Murugan, Kin Ghee Chee, Sreedharan Sechachalam, Tun-Lin Foo
BACKGROUND: Concomitant distal radius and distal ulna metaphysis or head fractures (DRUF) are uncommon and acceptable results have been reported from cast immobilisation and internal fixation. METHODS: We reviewed the charts of 1094 patients treated for distal radius fracture at our institution in a two year period from 2009 to 2010. 24 patients with concomitant DRUF with were treated by cast immobilisation (group 1, n = 11), internal fixation of both bones (group 2, n = 7), internal fixation of radius alone (group 3, n = 2), and internal fixation of radius with distal ulna resection (group 4, n = 4)...
October 2015: Hand Surgery
Shuang-shuang Liu, Ji-yun Huang, Gui-feng Xiao, Wei Yin, Zhao-Xiao-Nan Lin, Ying-mei Lu
OBJECTIVE: To observe the three-dimensional distribution of vessels, and to establish a new method for measurement of blood flow velocity in mice cerebral cortex using two-photon laser scanning microscopy and fluorescence probe labeling technique. METHODS: The mouse was made cranial window surgery and injected Texas-Red through tail vein after anesthetized. The three-dimensional imaging of vessel was obtained through z-stack scanning, and blood flow velocity was quantified through line scanning...
May 2015: Chinese Journal of Applied Physiology
Chen-Hsiang Lee, Lin-Hui Su, Fang-Ju Chen, Ya-Feng Tang, Chia-Chin Li, Chun-Chih Chien, Jien-Wei Liu
This study compared treatment outcomes of adult patients with bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae (ESBL-EK) receiving flomoxef versus those receiving a carbapenem as definitive therapy. In propensity score matching (PSM) analysis, case patients receiving flomoxef shown to be active in vitro against ESBL-EK were matched with controls who received a carbapenem. The primary endpoint was 30-day crude mortality. The flomoxef group had statistically significantly higher sepsis-related mortality (27...
December 2015: International Journal of Antimicrobial Agents
Kyaw Linn, Alexander Fay, Katherine Meddles, Sara Isbell, Phyo Nay Lin, Cho Thair, Jodi Heaps, Robert Paul, Soe Soe Mar
OBJECTIVE: We determined the effect of perinatally acquired HIV on neurocognition in Myanmar children treated with antiretroviral therapy by comparison to demographically matched seronegative children. BACKGROUND: Myanmar has one of the highest HIV-1 prevalence rates in Southeast Asia. Studies from other resource-poor countries have shown that HIV-infected children differ in socioeconomic, nutritional and caregiver status compared to normal controls. Some vertically infected orphans in Myanmar reside separately from HIV-uninfected children in separate orphanages, thus the demographic variables of interest are naturally controlled...
December 2015: Pediatric Neurology
Li Liu, Daizhi Yang, Yan Zhang, Shuo Lin, Xueying Zheng, Shaoda Lin, Lishu Chen, Xiuwei Zhang, Lu Li, Ganxiong Liang, Bin Yao, Jinhua Yan, Jianping Weng
BACKGROUND: Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM. METHODS: This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year...
November 2015: Diabetes/metabolism Research and Reviews
Yi-Hsin Liang, Yu-Yun Shao, Ho-Min Chen, Chiu-Lin Lai, Zhong-Zhe Lin, Raymond Nien-Chen Kuo, Ann-Lii Cheng, Kun-Huei Yeh, Mei-Shu Lai
OBJECTIVE: Because the number of long-term survivors of colorectal cancer has increased, second primary cancer has become an important issue. However, previous studies were heterogeneous in design, and few data for Asia-Pacific area were available. METHODS: This was a retrospective population-based study conducted using the national database of the Taiwan Cancer Registry. Patients who have histology-proven primary colon cancer and rectal cancer from 1995 to 2005 were enrolled in this study...
November 2015: Japanese Journal of Clinical Oncology
Jason M Aliotta, Mandy Pereira, Edmund H Sears, Mark S Dooner, Sicheng Wen, Laura R Goldberg, Peter J Quesenberry
BACKGROUND: Our group has previously demonstrated that murine whole bone marrow cells (WBM) that internalize lung-derived extracellular vesicles (LDEVs) in culture express pulmonary epithelial cell-specific genes for up to 12 weeks. In addition, the lungs of lethally irradiated mice transplanted with lung vesicle-modulated marrow have 5 times more WBM-derived type II pneumocytes compared to mice transplanted with unmanipulated WBM. These findings indicate that extracellular vesicle modification may be an important consideration in the development of marrow cell-based cellular therapies...
2015: Journal of Extracellular Vesicles
Siew C Ng, Zhirong Zeng, Ola Niewiadomski, Whitney Tang, Sally Bell, Michael A Kamm, Pinjin Hu, H Janaka de Silva, Madunil A Niriella, W S A A Yasith Udara, David Ong, Khoon Lin Ling, Choon Jin Ooi, Ida Hilmi, Khean Lee Goh, Qin Ouyang, Yu Fang Wang, Kaichun Wu, Xin Wang, Pises Pisespongsa, Sathaporn Manatsathit, Satimai Aniwan, Julajak Limsrivilai, Jeffri Gunawan, Marcellus Simadibrata, Murdani Abdullah, Steve W C Tsang, Fu Hang Lo, Aric J Hui, Chung Mo Chow, Hon Ho Yu, Mo Fong Li, Ka Kei Ng, Jessica Y L Ching, Victor Chan, Justin C Y Wu, Francis K L Chan, Minhu Chen, Joseph J Y Sung
BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013...
January 2016: Gastroenterology
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