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Karin Kfir-Elirachman, Rona Ortenberg, Bella Vizel, Michal J Besser, Iris Barshack, Jacob Schachter, Yael Nemlich, Gal Markel
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role in melanoma, including facilitation of cell proliferation and suppression of infiltrating lymphocytes, which are consistent with its value as a marker for poor prognosis in melanoma patients. Here we show that BRAFV600E melanoma cells treated with BRAF and MEK inhibitors (MAPKi) downregulate CEACAM1 mRNA and protein expression in a dose- and exposure time-dependent manners. Indeed, there is a significant correlation between the presence of BRAFV600E and CEACAM1 expression in melanoma specimens obtained from 45 patients...
March 17, 2018: Neoplasia: An International Journal for Oncology Research
Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Jeffrey K Holden, Christian N Cunningham
The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD) protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer...
March 20, 2018: Cancers
Ramesh Raju Vetukuri, Sandeep Kushwaha, Diya Sen, Stephen C Whisson, Kurt Lamour, Laura Grenville-Briggs
Phytophthora colocasiae is a phytopathogenic oomycete that causes leaf blight and corm rot on taro (Colocasia esculenta), an important staple crop in the tropics. The impact of P. colocasiae is a serious concern for food security in Asian and Oceanic regions. Vietnamese strain 7290 of P. colocasiae was sequenced (Illumina) to assemble a draft genome of 56.6 Mb, comprised of 19853 scaffolds and 19984 predicted protein-coding genes. As in other Phytophthora species, P. colocasiae possesses numerous pathogenicity-related genes, such as the RxLR class of effectors...
March 20, 2018: Molecular Plant-microbe Interactions: MPMI
Mathieu Niquille, Greta Limoni, Foivos Markopoulos, Christelle Cadilhac, Julien Prados, Anthony Holtmaat, Alexandre Dayer
Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3A R-expressing Hmx3+ cells located in the preoptic area (POA)...
March 20, 2018: ELife
Alexander N Orekhov, Igor A Sobenin
Atherosclerotic diseases are the leading cause of mortality in industrialized countries. Correspondingly, studying the pathogenesis of atherosclerosis and developing new methods of its diagnostic and treatment remain in the focus of current medicine and health care. This review aims to discuss the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis. In particular, the generally accepted hypothesis about the key role of oxidized LDL in atherogenesis is questioned, and an alternative concept of multiple modification of LDL is presented...
March 20, 2018: Current Medicinal Chemistry
Daniel Freund, Silke Brilloff, Tamer Ghazy, Stephan Kirschner, Gabor Gäbel, Irene Hinterseher, Norbert Weiss, Adrian Mahlmann
BACKGROUND: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects. PATIENTS AND METHODS: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken...
March 20, 2018: VASA. Zeitschrift Für Gefässkrankheiten
Daniel Lüdke, Charlotte Roth, Denise Hartken, Marcel Wiermer
The Arabidopsis nuclear transport receptor IMPORTIN-α3/MOS6 (MODIFIER OF SNC1, 6) is required for constitutive defense responses of the auto-immune mutant snc1 (suppressor of npr1-1, constitutive 1) and contributes to basal disease resistance, suggesting a role in nuclear import of defense-regulatory cargo proteins. We recently showed that MOS6 selectively interacts with TN13, a TIR-NBS protein involved in basal resistance to Pseudomonas syringae pv. tomato (Pst) DC3000 lacking the effectors AvrPto and AvrPtoB...
March 20, 2018: Plant Signaling & Behavior
Chittappen K Prajeeth, Jochen Huehn, Martin Stangel
No abstract text is available yet for this article.
February 2018: Neural Regeneration Research
Duanyang Zhai, Chunhui Cui, Lang Xie, Lianxu Cai, Jinlong Yu
Metastasis is the primary cause of mortality in colorectal cancer (CRC), the mechanism of which remains unclear. In the present study, by detecting mRNA expression using a reverse transcription-quantitative polymerase chain reaction (qPCR), it was revealed that sterol regulatory element-binding protein 1 (SREBP1) is highly expressed in CRC. Using a cell wound healing assay and a cell invasion assay, a novel metastasis-promoting role for SREBP1 in CRC was identified. Furthermore, snail family transcriptional repressor 1 (SNAIL) was identified as a key downstream effector of SREBP1 in CRC by the use of small interfering RNA against SNAIL...
April 2018: Oncology Letters
Wei Zhang, Xinyan Xie, Huijing Mi, Jinwan Sun, Shaoxue Ding, Lijuan Li, Hui Liu, Huaquan Wang, Rong Fu, Zonghong Shao
Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis that lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disease. Different levels or mechanisms of natural killer (NK) cells in patients with MDS have been measured in previous studies, making it challenging to understand the pathogenesis of NK cytotoxicity. The present study investigated the frequency of NK cell-mediated antibody-dependent cellular cytotoxicity and explored the function of NK cells by their activating receptors, inhibition signals, degranulation and cytotoxicity factors...
April 2018: Oncology Letters
Gopal R Gopinath, Hannah R Chase, Jayanthi Gangiredla, Athmanya Eshwar, Hyein Jang, Isha Patel, Flavia Negrete, Samantha Finkelstein, Eunbi Park, TaeJung Chung, YeonJoo Yoo, JungHa Woo, YouYoung Lee, Jihyeon Park, Hyerim Choi, Seungeun Jeong, Soyoung Jun, Mijeong Kim, Chaeyoon Lee, HyeJin Jeong, Séamus Fanning, Roger Stephan, Carol Iversen, Felix Reich, Günter Klein, Angelika Lehner, Ben D Tall
Background: Malonate utilization, an important differential trait, well recognized as being possessed by six of the seven Cronobacter species is thought to be largely absent in Cronobacter sakazakii (Csak). The current study provides experimental evidence that confirms the presence of a malonate utilization operon in 24 strains of sequence type (ST) 64, obtained from Europe, Middle East, China, and USA; it offers explanations regarding the genomic diversity and phylogenetic relatedness among these strains, and that of other C...
2018: Gut Pathogens
Maria A Schumacher, Chris D den Hengst, Matthew J Bush, T B K Le, Ngat T Tran, Govind Chandra, Wenjie Zeng, Brady Travis, Richard G Brennan, Mark J Buttner
Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DNA-binding protein related to MerR regulators, but lacks coiled-coil dimerization and effector-binding domains characteristic of classical MerR proteins. Hence, the molecular function of the protein has been unclear. Here we show that BldC is indeed a DNA-binding protein and controls a regulon that includes other key developmental regulators...
March 19, 2018: Nature Communications
Sreeharsha Gurrapu, Emanuela Pupo, Giulia Franzolin, Letizia Lanzetti, Luca Tamagnone
Semaphorin 4C (Sema4C) expression in human breast cancers correlates with poor disease outcome. Surprisingly, upon knock-down of Sema4C or its receptor PlexinB2 in diverse mammary carcinoma cells (but not their normal counterparts), we observed dramatic growth inhibition associated with impairment of G2/M phase transition, cytokinesis defects and the onset of cell senescence. Mechanistically, we demonstrated a Sema4C/PlexinB2/LARG-dependent signaling cascade that is required to maintain critical RhoA-GTP levels in cancer cells...
March 19, 2018: Cell Death and Differentiation
Jacqueline Corbitt, Jun Seok Yeo, C Ian Davis, Michele LeRoux, Paul A Wiggins
The Type VI Secretion System (T6SS) inhibits growth of neighboring bacterial cells through a contact-mediated mechanism. We describe a detailed characterization of the protein localization dynamics in the Pseudomonas aeruginosa T6SS. It has been proposed that Type VI secretion process is driven by a conformational-change induced contraction of the T6SS sheath. However, although the contraction of an optically resolvable TssBC sheath and the subsequent localization of ClpV are observed in Vibrio cholerae , coordinated assembly and disassembly of TssB and ClpV are observed without TssB contraction in P...
March 19, 2018: Journal of Bacteriology
Beatrice Bergström, Hans Carlsten, Anna-Karin Hultgård Ekwall
BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro...
March 20, 2018: Arthritis Research & Therapy
James H Park, Antonina Roll-Mecak
Cells depend on the asymmetric distribution of their components for homeostasis, differentiation and movement. In no other cell type is this requirement more critical than in the neuron where complex structures are generated during process growth and elaboration and cargo is transported over distances several thousand times the cell body diameter. Microtubules act both as dynamic structural elements and as tracks for intracellular transport. Microtubules are mosaic polymers containing multiple tubulin isoforms functionalized with abundant posttranslational modifications that are asymmetrically distributed in neurons...
March 16, 2018: Current Opinion in Neurobiology
Young Min Kim, Jin Se Park, Sang Kyung Kim, Kyung Min Jung, Young Sun Hwang, Mookyoung Han, Hong Jo Lee, Hee Won Seo, Jeong-Yong Suh, Beom Ku Han, Jae Yong Han
Modern genetic techniques, enable the use of animal bioreactor systems for the production and functional enhancement of anti-cancer antibodies. Chicken is the most efficient animal bioreactor for the production of anti-cancer antibodies because of its relatively short generation time, plentiful reproductive capacity, and daily deposition in the egg white. Although several studies have focused on the production of anti-cancer antibodies in egg white, in-depth studies of the biological activity and physiological characteristics of transgenic chicken-derived anti-cancer antibodies have not been fully carried out...
March 13, 2018: Biomaterials
Huan Liu, Andrew R Osterburg, Jennifer Flury, Shuo Huang, Francis X McCormack, Stephania A Cormier, Michael T Borchers
Background: Respiratory syncytial virus (RSV) is a common cause of respiratory tract infection in vulnerable populations. Natural killer (NK) cells and dendritic cells (DC) are important for the effector functions of both cell types following infection. Methods: Wild type and NKG2D deficient mice were infected with RSV. Lung pathology, was assessed by histology. DC function and phenotype was evaluated by ELISA and flow cytometry. The expression of NKG2D ligands on lung and lymph node DCs was measured by immunostaining and flow cytometry...
March 15, 2018: Journal of Infectious Diseases
Qi-Feng He, Yong Xu, Jun Li, Zheng-Ming Huang, Xiu-Hui Li, Xiaochen Wang
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines. Such dysfunctional CD8+ T cells serve as a barrier in successful cancer elimination...
March 15, 2018: Briefings in Functional Genomics
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