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Lijun Liu, Tarjani M Thaker, Daniel M Freed, Nicole Frazier, Ketan Malhotra, Mark A Lemmon, Natalia Jura
In the active HER receptor dimers, kinases play distinct roles; one is the catalytically active kinase and the other is its allosteric activator. This specialization enables signaling by the catalytically inactive HER3, which functions exclusively as an allosteric activator upon heterodimerization with other HER receptors. It is unclear whether the allosteric activation mechanism evolved before HER receptors functionally specialized. We determined the crystal structure of the kinase domain of the only EGF receptor in Caenorhabditis elegans, LET-23...
February 6, 2018: Structure
Kimberley Gauthier, Christian E Rocheleau
Epidermal growth factor receptor (EGFR)-mediated activation of the canonical Ras/MAPK signaling cascade is responsible for cell proliferation and cell growth. This signaling pathway is frequently overactivated in epithelial cancers; therefore, studying regulation of this pathway is crucial not only for our fundamental understanding of cell biology but also for our ability to treat EGFR-related disease. Genetic model organisms such as Caenorhabditis elegans, a hermaphroditic nematode, played a vital role in identifying components of the EGFR/Ras/MAPK pathway and delineating their order of function, and continues to play a role in identifying novel regulators of the pathway...
2017: Methods in Molecular Biology
Pu Pu, Craig E Stone, Joshua T Burdick, John I Murray, Meera V Sundaram
Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration, and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the Caenorhabditis elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation...
March 2017: Genetics
Matt Crook, Awani Upadhyay, Liyana J Ido, Wendy Hanna-Rose
Identification of pro-cell-survival signaling pathways has implications for cancer, cardiovascular and neurodegenerative disease. We show that the Caenorhaditis elegans epidermal growth factor receptor LET-23 has a pro-survival function in counteracting excitotoxicity, and we identify novel molecular players required for this pro-survival signaling. uv1 sensory cells in the C. elegans uterus undergo excitotoxic death in response to activation of the OSM-9/OCR-4 TRPV channel by the endogenous agonist nicotinamide...
September 7, 2016: G3: Genes—Genomes—Genetics
Stephane Flibotte, Bo Ram Kim, Emily Van de Laar, Louise Brown, Nadeem Moghal
Signaling by the epidermal growth factor receptor (EGFR) generates diverse developmental patterns. This requires precise control over the location and intensity of signaling. Elucidation of these regulatory mechanisms is important for understanding development and disease pathogenesis. In Caenorhabditis elegans, LIN-3/EGF induces vulval formation in the mid-body, which requires LET-23/EGFR activation only in P6.p, the vulval progenitor nearest the LIN-3 source. To identify mechanisms regulating this signaling pattern, we screened for mutations that cooperate with a let-23 gain-of-function allele to cause ectopic vulval induction...
July 1, 2016: Developmental Biology
Ching-Hua Hsieh, Cheng-Shyuan Rau, Shao-Chun Wu, Johnson Chia-Shen Yang, Yi-Chan Wu, Tsu-Hsiang Lu, Siou-Ling Tzeng, Chia-Jung Wu, Chia-Wei Lin
BACKGROUND: To examine the circulating microRNA (miRNA) expression profile in a mouse model of diet-induced obesity (DIO) with subsequent weight reduction achieved via low-fat diet (LFD) feeding. RESULTS: Eighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal %) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal % high-fat diet (HFD) for 12 weeks; and (3) DIO + LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10...
2015: BMC Genomics
Brita S Sørensen, Michael R Horsman, Jan Alsner, Jens Overgaard, Marco Durante, Michael Scholz, Thomas Friedrich, Niels Bassler
BACKGROUND: The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. MATERIAL AND METHODS: CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days)...
2015: Acta Oncologica
Dawn C Newcomb, Jacqueline Yvonne Cephus, Madison G Boswell, John M Fahrenholz, Emily W Langley, Amy S Feldman, Weisong Zhou, Daniel E Dulek, Kasia Goleniewska, Kimberly B Woodward, Carla M Sevin, Robert G Hamilton, Jay K Kolls, R Stokes Peebles
BACKGROUND: Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. OBJECTIVE: We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. METHODS: IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma...
October 2015: Journal of Allergy and Clinical Immunology
Thomas Yates, Joe Henson, Charlotte Edwardson, Danielle H Bodicoat, Melanie J Davies, Kamlesh Khunti
OBJECTIVE: We investigate differences between White and South Asian (SA) populations in levels of objectively measured and self-reported physical activity. DESIGN: Cross-sectional study. SETTING: Leicestershire, UK, 2010-2011. PARTICIPANTS: Baseline data were pooled from two diabetes prevention trials that recruited a total of 4282 participants from primary care with a high risk score for type 2 diabetes. For this study, 2843 White (age=64±8, female=37%) and 243 SA (age=58±9, female=34%) participants had complete physical activity data and were included in the analysis...
July 23, 2015: BMJ Open
Eirik Malinen, Åste Søvik
BACKGROUND: Dose painting is a concept that may increase the tumor control probability (TCP). In particle therapy of hypoxic tumors, it may also be beneficial to redistribute the linear energy transfer (LET) so that the oxygen effect is minimized; so-called LET painting. The purpose of the present study was to use TCP estimates for comparing dose and LET painting of hypoxic tumors. MATERIAL AND METHODS: Protons, lithium ions and carbon ions were considered. Tumor images tentatively depicting hypoxia were used as input...
2015: Acta Oncologica
D A Granville, D B Flint, G O Sawakuchi
PURPOSE: To characterize the response of Al2O3:C optically stimulated luminescence (OSL) detectors (OSLDs) exposed to therapeutic proton beams of differing beam quality. METHODS: We prepared Al2O3:C OSLDs from the same material as commercially available nanoDot dosimeters (Landauer, Inc). We irradiated the OSLDs in modulated proton beams of varying quality, as defined by the residual range. An absorbed dose to water of 0.2 Gy was delivered to all OSLDs with the residual range values varying from 0...
June 2015: Medical Physics
J Seco, D Giantsoudi, B R Eaton, J A Adams, H Paganetti, S MacDonald
PURPOSE: To investigate the trade-off between vertebral column sparing and thecal-sac target coverage in craniospinal irradiation (CSI) of pediatric patients treated with passive-scattering (PS) and intensity modulated (IMPT) proton therapy. METHODS: We selected 2 pediatric patients treated with PS CSI for medulloblastoma. Spinal irradiation was re-planned with IMPT. For all cases, we assumed prescription dose of 23.4 Gy(RBE), with the spinal canal receiving at least 95% of 23...
June 2015: Medical Physics
Daniel M Freed, Diego Alvarado, Mark A Lemmon
Ligand-induced receptor dimerization has traditionally been viewed as the key event in transmembrane signalling by epidermal growth factor receptors (EGFRs). Here we show that the Caenorhabditis elegans EGFR orthologue LET-23 is constitutively dimeric, yet responds to its ligand LIN-3 without changing oligomerization state. SAXS and mutational analyses further reveal that the preformed dimer of the LET-23 extracellular region is mediated by its domain II dimerization arm and resembles other EGFR extracellular dimers seen in structural studies...
2015: Nature Communications
Le-Rong Wang, Hai-Long Wang, Jia-Qing Lu
OBJECTIVE: To observe the clinical therapeutic effect of blood-letting plus acupuncture intervention for acute facial paralysis with pain (damp-heat type of liver and gallbladder). METHODS: A total of 120 cases of acute facial paralysis with pain were randomly and equally divided into control group and treatment group. Patients of the control group were treated by simple acupuncture therapy only, and patients of the treatment group treated by acupuncture plus bloodletting at the ipsilateral Yangbai(GB 14) and Quanliao (SI 18), and Dazhui (GV 14) and Yifeng (TE 17), alternatively...
April 2015: Zhen Ci Yan Jiu, Acupuncture Research
Gauri Shishodia, Shirish Shukla, Yogesh Srivastava, Shashank Masaldan, Sumita Mehta, Suresh Bhambhani, Shashi Sharma, Ravi Mehrotra, Bhudev Chandra Das, Alok Chandra Bharti
BACKGROUND: Present study provides clinical evidence of existence of a functional loop involving miR-21 and let-7a as potential regulators of aberrant STAT3 signaling recently reported by our group in an experimental setup (Shishodia et al. BMC Cancer 2014, 14:996). The study is now extended to a set of cervical tissues that represent natural history of human papillomavirus (HPV)-induced tumorigenic transformation. MATERIALS AND METHODS: Cervical tissues from histopathologically-confirmed pre-cancer (23) and cancer lesions (56) along with the normal control tissues (23) were examined for their HPV infection status, expression level of miR-21 & let-7a and STAT3 & pSTAT3 (Y705) by PCR-based genotyping, quantitative real-time PCR and immunoblotting...
2015: Molecular Cancer
Yundan Liang, Gaofeng Zhao, Ruifen Sun, Yuanyi Mao, Gangqin Li, Xueyan Chen, Linbo Gao, Zeqing Hu
BACKGROUND: Let-7 family plays a critical role in the pathogenesis of major depressive disorder (MDD). Genetic polymorphisms in the promoters of miRNA may influence individual׳s susceptibility to diseases. The purpose of this study was to investigate the association between rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family and the risk of MDD. METHOD: Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assays were used to analyze the rs10877887 and rs13293512 polymorphisms in 237 MDD patients and 296 controls...
September 1, 2015: Journal of Affective Disorders
Yuanshuai Fu, Junling Zhang, Zhiyi Shi, Guyue Wang, Wejuan Li, Liang Jia
Dicer is critical for producing mature microRNAs (miRNAs) from precursor molecules and small interfering RNAs and plays an important role in controlling development and metabolism. In the present study, we cloned the flounder dicer gene, which is 6585 nucleotides (nt), including a 5'-untranslated region (UTR) of 231 nt, a 3'-UTR of 663 nt and an open reading frame of 5691 nt encoding a polypeptide of 1897 amino acids, and analyzed the conservation and expression pattern of dicer. The tissue distribution analysis indicated that dicer is abundantly expressed in the brain, heart, liver, spleen, stomach, kidney, gill, muscle, intestine and gonad of adult fish...
October 2015: Fish Physiology and Biochemistry
Sylvia Weilner, Susanna Skalicky, Benjamin Salzer, Verena Keider, Michael Wagner, Florian Hildner, Christian Gabriel, Peter Dovjak, Peter Pietschmann, Regina Grillari-Voglauer, Johannes Grillari, Matthias Hackl
Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level and are known to take part in the control of bone formation and bone resorption. In addition, it is known that miRNAs are secreted by many cell types and can transfer "messages" to recipient cells. Thus, circulating miRNAs might not only be useful as surrogate biomarkers for the diagnosis or prognosis of pathological conditions, but could be actively modulating tissue physiology...
October 2015: Bone
Wieslaw L Nowinski, Thant Shoon Let Thaung, Beng Choon Chua, Su Hnin Wut Yi, Yili Yang, Andrzej Urbanik
Our objective was to construct a 3D, interactive, and reference atlas of the extracranial vasculature spatially correlated with the intracranial blood vessels, cranial nerves, skull, glands, and head muscles.The atlas has been constructed from multiple 3T and 7T magnetic resonance angiogram (MRA) brain scans, and 3T phase contrast and inflow MRA neck scans of the same specimen in the following steps: vessel extraction from the scans, building 3D tubular models of the vessels, spatial registration of the extra- and intracranial vessels, vessel editing, vessel naming and color-coding, vessel simplification, and atlas validation...
April 2015: Neuroradiology Journal
David Kalfert, Martin Pesta, Vlastimil Kulda, Ondrej Topolcan, Ales Ryska, Petr Celakovsky, Jan Laco, Marie Ludvikova
BACKGROUND/AIM: MicroRNAs (miRs) are non-coding RNA molecules regulating diverse cellular processes essential in carcinogenesis. Little is known regarding miRs in head and neck squamous cell cancer (HNSCC). The aim of the present study was to investigate miRs in relation to the clinico pathological features of site-specific HNSCC. MATERIALS AND METHODS: The study comprised of 51 patients with HNSCC (23 oropharyngeal, 24 laryngeal and 4 hypopharyngeal carcinomas)...
April 2015: Anticancer Research
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