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https://www.readbyqxmd.com/read/28938607/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#1
Sasha J Ruiz-Torres, Nancy M Benight, Rebekah A Karns, Elyse E Lower, Jun-Lin Guan, Susan E Waltz
Breast cancer stem cells (BCSCs), which drive tumor progression, recurrence, and metastasis, are considered a major challenge for breast cancer treatments, thus the discovery of novel pathways regulating BCSC maintenance remains essential to develop new strategies to effectively target this population and combat disease mortality. The HGFL-RON signaling is overexpressed in human breast cancers and is associated with increased breast cancer progression, metastasis, and poor prognosis. Here, we report that overexpression of RON/MST1R and HGFL/MST1 in cell lines and primary tumors increases BCSC self-renewal, numbers, and tumorigenic potential after syngeneic transplantation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938533/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#2
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938470/genetic-disruption-of-21-hydroxylase-in-zebrafish-causes-interrenal-hyperplasia
#3
Helen Eachus, Andreas Zaucker, James A Oakes, Aliesha Griffin, Meltem Weger, Tülay Güran, Angela Taylor, Abigail Harris, Andy Greenfield, Jonathan L Quanson, Karl-Heinz Storbeck, Vincent T Cunliffe, Ferenc Müller, Nils Krone
Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we have developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the Cyp21a2 protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo...
September 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938438/targeted-disruption-of-yap-and-taz-impairs-the-maintenance-of-the-adrenal-cortex
#4
Adrien Levasseur, Guillaume St-Jean, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway. They act as major regulators of stem cell maintenance, cell growth and differentiation. To characterize their roles in the adrenal cortex, we generated a mouse model in which Yap and Taz were conditionally deleted in steroidogenic cells (Yapflox/flox;Tazflox/flox;Nr5a1cre/+). Male Yapflox/flox;Tazflox/flox;Nr5a1cre/+ mice were characterized by an age-dependent degeneration of the adrenal cortex associated with an increase in apoptosis and a progressive reduction in the expression levels of steroidogenic genes...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938014/intestinal-helminth-infection-drives-carcinogenesis-in-colitis-associated-colon-cancer
#5
Eva Pastille, Annika Frede, Henry J McSorley, Jessica Gräb, Alexandra Adamczyk, Sebastian Kollenda, Wiebke Hansen, Matthias Epple, Jan Buer, Rick M Maizels, Robert Klopfleisch, Astrid M Westendorf
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation...
September 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28937281/tracking-by-detection-of-surgical-instruments-in-minimally-invasive-surgery-via-the-convolutional-neural-network-deep-learning-based-method
#6
Zijian Zhao, Sandrine Voros, Ying Weng, Faliang Chang, Ruijian Li
BACKGROUND: Worldwide propagation of minimally invasive surgeries (MIS) is hindered by their drawback of indirect observation and manipulation, while monitoring of surgical instruments moving in the operated body required by surgeons is a challenging problem. Tracking of surgical instruments by vision-based methods is quite lucrative, due to its flexible implementation via software-based control with no need to modify instruments or surgical workflow. METHODS: A MIS instrument is conventionally split into a shaft and end-effector portions, while a 2D/3D tracking-by-detection framework is proposed, which performs the shaft tracking followed by the end-effector one...
September 22, 2017: Computer Assisted Surgery (Abingdon, England)
https://www.readbyqxmd.com/read/28936523/mesoporous-zno-nanocapsules-for-the-induction-of-enhanced-antigen-specific-immunological-responses
#7
Sumbul Afroz, Himadri Medhi, Somedutta Maity, Gillipsie Minhas, Srikanth Battu, Jeevan Giddaluru, Koushi Kumar, Pradip Paik, Nooruddin Khan
The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions...
September 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28936464/innate-immune-responses-to-cryptococcus
#8
Lena J Heung
Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus, primarily the species C...
September 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/28936196/anti-inflammatory-targets-for-the-treatment-of-reperfusion-injury-in-stroke
#9
REVIEW
Atsushi Mizuma, Midori A Yenari
While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28935958/differential-regulation-of-effector-and-regulatory-t-cell-function-by-blimp1
#10
Rashmi Bankoti, Chihiro Ogawa, Truc Nguyen, Lena Emadi, Michael Couse, Soofia Salehi, Xuemo Fan, Deepti Dhall, Yizhou Wang, Jordan Brown, Vincent Funari, Jie Tang, Gislâine A Martins
The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935957/modulation-of-cyclic-nucleotide-mediated-cellular-signaling-and-gene-expression-using-photoactivated-adenylyl-cyclase-as-an-optogenetic-tool
#11
Meenakshi Tanwar, Lohit Khera, Nemneineng Haokip, Rajeev Kaul, Aruna Naorem, Suneel Kateriya
Cyclic nucleotide signaling pathway plays a significant role in various biological processes such as cell growth, transcription, inflammation, in microbial pathogenesis, etc. Modulation of cyclic nucleotide levels by optogenetic tools has overcome certain limitations of studying transduction cascade by pharmacological agents and has allowed several ways to modulate biological processes in a spatiotemporal manner. Here, we have shown the optogenetic modulation of the cyclooxygenase 2 (Cox-2) gene expression and their downstream effector molecule (PGE2) in HEK-293T cells and the development process of Dictyostelium discoideum via modulating the cyclic nucleotide (cAMP) signaling pathway utilizing photoactivated adenylyl cyclases (PACs) as an optogenetic tool...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#12
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28935716/proteomic-analysis-of-phytophthora-infestans-reveals-the-importance-of-cell-wall-proteins-in-pathogenicity
#13
Svante Resjö, Maja Brus, Ashfaq Ali, Harold J G Meijer, Marianne Sandin, Francine Govers, Fredrik Levander, Laura Grenville-Briggs, Erik Andreasson
The oomycete Phytophthora infestans is the most harmful pathogen of potato. It causes the disease late blight, which generates increased yearly costs of up to one billion euro in the EU alone and is difficult to control. We have performed a large-scale quantitative proteomics study of six P. infestans life stages with the aim to identify proteins that change in abundance during development, with a focus on pre-infectious life stages. Over 10 000 peptides from 2061 proteins were analysed. We identified a number of abundance profiles of proteins that were up- or downregulated in different combinations of life stages...
September 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28935575/non-pathological-infection-of-macaques-by-an-attenuated-mycobacterial-vaccine-is-not-reactivated-in-the-setting-of-hiv-coinfection
#14
Taylor Wayne Foreman, Ashley Victoria Veatch, Denae Nadine LoBato, Peter John Didier, Lara Angela Doyle-Meyers, Kasi Elizabeth Russell-Lodrigue, Andrew Alan Lackner, Konstantin Gus Kousoulas, Shabaana Abdul Khader, Deepak Kaushal, Smriti Mehra
Failure to replace BCG with efficacious anti-TB vaccines have prompted out-of-the-box thinking, including pulmonary vaccination in order to elicit local immunity. MtbΔsigH, a stress-response attenuated strain, protected against lethal TB when used to vaccinate macaques via inhalation. While live mycobacterial vaccines show promising efficacy, HIV co-infection and the resulting immunodeficiency prompts safety concerns about their use. We assessed the persistence and safety of MtbΔsigH, delivered directly to the lungs, in the setting of HIV coinfection...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935555/vaccination-with-a-dna-vaccine-encoding-toxoplasma-gondii-rop54-induces-protective-immunity-against-toxoplasmosis-in-mice
#15
Wen-Bin Yang, Dong-Hui Zhou, Yang Zou, Kai Chen, Qing Liu, Jin-Lei Wang, Xing-Quan Zhu, Guang-Hui Zhao
Toxoplasma gondii is an obligatory intracellular protozoan, which infects most of the warm-blooded animals, causing serious public health problems and enormous economic losses worldwide. The rhoptry effector protein 54 (ROP54) has been indicated as a virulence factor that promotes Toxoplasma infection by modulating GBP2 loading onto parasite-containing vacuoles, which can modulate some aspects of the host immune response. In order to evaluate the immuno-protective value of ROP54, we constructed a eukaryotic recombinant plasmid expressing T...
September 18, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#16
Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, Xiao-Feng Chen
LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4(+)CD25(-) T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4(+) T cells directly ex vivo and primarily in the CD4(+)CD25(-) fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27...
September 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28935395/the-role-of-tec-kinase-signaling-pathways-in-the-development-of-mallory-denk-bodies-in-balloon-cells-in-alcoholic-hepatitis
#17
N Afifiyan, B Tillman, B A French, O Sweeny, M Masouminia, S Samadzadeh, S W French
Several research strategies have been used to study the pathogenesis of alcoholic hepatitis (AH). These strategies have shown that various signaling pathways are the target of alcohol in liver cells. However, few have provided specific mechanisms associated with Mallory-Denk Bodies (MDBs) formed in Balloon cells in AH. The formation of MDBs in these hepatocytes is an indication that the mechanisms of protein quality control have failed. The MDB is the result of aggregation and accumulation of proteins in the cytoplasm of balloon degenerated liver cells...
September 18, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28935250/engineered-cells-for-costimulatory-enhancement-combined-with-il-21-enhance-the-generation-of-pd-1-disrupted-ctls-for-adoptive-immunotherapy
#18
Jie Shao, Qiuping Xu, Shu Su, Fanyan Meng, Zhengyun Zou, Fangjun Chen, Juan Du, Xiaoping Qian, Baorui Liu
Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28935173/coxiella-burnetiias-a-useful-tool-to-investigate-bacteria-friendly-host-cell-compartments
#19
REVIEW
Julian Pechstein, Jan Schulze-Luehrmann, Anja Lührmann
Coxiella burnetii is an obligate intracellular and airborne pathogen which can cause the zoonotic disease Q fever. After inhalation of contaminated aerosols alveolar macrophages are taking up C. burnetii into a phagosome. This phagosome matures to a very large vacuole called the C. burnetii-containing vacuole (CCV). Host endogenous and bacterial driven processes lead to the biogenesis of this unusual compartment, which resembles partially a phagolysosome. However, there are several important differences to the classical phagolysosome, which are crucial for the ability of C...
September 14, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28934905/talen-mediated-targeted-editing-of-the-gde5-gene-suppresses-fibroblastic-cell-proliferation
#20
Minako Nakamura, Thanutchaporn Kumrungsee, Tetsushi Sakuma, Takashi Yamamoto, Noriyuki Yanaka
In this study, we investigated the physiological function of glycerophosphodiesterase 5 (GDE5) in the proliferation of NIH3T3 fibroblasts. We used transcription activator-like effector nuclease (TALEN) in NIH3T3 cells with an intron targeting-mediated GDE5 gene knockout. The heterozygously GDE5-targeted NIH3T3 fibroblasts were isolated and showed decreased cell proliferation and up-regulation of EGFR mRNA expression, indicating that GDE5 modulates fibroblastic cell proliferation.
September 22, 2017: Bioscience, Biotechnology, and Biochemistry
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