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https://www.readbyqxmd.com/read/28449081/the-coxiella-burnetii-type-ivb-secretion-system-t4bss-component-dota-is-released-secreted-during-infection-of-host-cells-and-during-in-vitro-growth-in-a-t4bss-dependent-manner
#1
Brandon E Luedtke, Saugata Mahapatra, Erika I Lutter, Edward I Shaw
Coxiella burnetii is a Gram-negative intracellular pathogen and is the causative agent of the zoonotic disease Q-fever. To cause disease, C. burnetii requires a functional type IVB secretion system (T4BSS) to transfer effector proteins required for the establishment and maintenance of a membrane bound parasitophorous vacuole (PV) and further modulation of host cell process. However, it is not clear how the T4BSS interacts with the PV membrane since neither a secretion pilus nor an extracellular pore forming apparatus has not been described...
April 25, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28449072/functions-of-galectins-as-self-non-self-recognition-and-effector-factors
#2
Gerardo R Vasta, Chiguang Feng, Nuria González-Montalbán, Justin Mancini, Lishi Yang, Kelsey Abernathy, Graeme Frost, Cheyenne Palm
Carbohydrate structures on the cell surface encode complex information that through specific recognition by carbohydrate-binding proteins (lectins), modulates interactions between cells, cells and the extracellular matrix, or mediates recognition of potential microbial pathogens. Galectins are a family of ß-galactoside-binding lectins, which are evolutionary conserved and have been identified in most organisms, from fungi to invertebrates and vertebrates, including mammals. Since their discovery in the 1970s, their biological roles, initially understood as limited to recognition of endogenous carbohydrate ligands in embryogenesis and development, have expanded in recent years by the discovery of their roles in tissue repair and regulation of immune homeostasis...
April 25, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28449057/the-streptomyces-master-regulator-bldd-binds-c-di-gmp-sequentially-to-create-a-functional-bldd2-c-di-gmp-4-complex
#3
Maria A Schumacher, Wenjie Zeng, Kim C Findlay, Mark J Buttner, Richard G Brennan, Natalia Tschowri
Streptomyces are ubiquitous soil bacteria that undergo a complex developmental transition coinciding with their production of antibiotics. This transition is controlled by binding of a novel tetrameric form of the second messenger, 3΄-5΄ cyclic diguanylic acid (c-di-GMP) to the master repressor, BldD. In all domains of life, nucleotide-based second messengers allow a rapid integration of external and internal signals into regulatory pathways that control cellular responses to changing conditions. c-di-GMP can assume alternative oligomeric states to effect different functions, binding to effector proteins as monomers, intercalated dimers or, uniquely in the case of BldD, as a tetramer...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448894/il-33-improves-the-suppressive-potential-of-regulatory-t-cells-in-patients-with-type-1-diabetes
#4
Monika Ryba-Stanisławowska, Laura Buksa, Agnieszka Brandt, Ulana Juhas, Małgorzata Myśliwiec
AIMS: The presented study was aimed to analyze the influence of IL-33 on regulatory T cells (Tregs) suppressive potential in patients with type 1 diabetes. METHODS: We analyzed the ability of IL-33 treated Tregs to inhibit the production of IFN-γ by effector T lymphocytes in an in vitro co-culture. The study group consisted of 22 patients with type 1 diabetes and 12 age and sex-matched healthy individuals. RESULTS: Our findings revealed that in vitro IL-33 treatment of Tregs derived from patients with type 1 diabetes resulted in quantitative as well as qualitative changes in this cell population, confirming immunoregulatory features of IL-33...
April 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28448738/site-specific-recruitment-of-epigenetic-factors-with-a-modular-crispr-cas-system
#5
Tobias Anton, Sebastian Bultmann
Dissecting the complex network of epigenetic modifications requires tools that combine precise recognition of DNA sequences with the capability to modify epigenetic marks. The CRISPR/Cas system has been proven to be a valuable addition to existing methodologies that fulfill these tasks. So far, sequence-specific editing of epigenetic modifications such as DNA methylation and histone posttranslational modifications relied on direct fusions of enzymatically inactivated Cas9 (dCas9) with epigenetic effectors. Here, we report a novel, modular system that facilitates the recruitment of any GFP-tagged protein to desired genomic loci...
February 23, 2017: Nucleus
https://www.readbyqxmd.com/read/28448636/successful-vitrification-of-pronuclear-stage-pig-embryos-with-a-novel-cryoprotective-agent-carboxylated-%C3%AE%C2%B5-poly-l-lysine
#6
Maki Kamoshita, Tsubasa Kato, Katsuyoshi Fujiwara, Takafumi Namiki, Kazuaki Matsumura, Suong-Hyu Hyon, Junya Ito, Naomi Kashiwazaki
Vitrification is a powerful tool for the efficient production of offspring derived from cryopreserved oocytes or embryos in mammalian species including domestic animals. Genome editing technologies such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated (Cas)9 are now available even for domestic species, suggesting that the vitrification of embryos at the pronuclear stage (PN) will be more important because they could provide genomic host cells to be targeted by TALENs or CRISPR/Cas9...
2017: PloS One
https://www.readbyqxmd.com/read/28448594/novel-in-natural-infection-subdominant-hiv-1-cd8-t-cell-epitopes-revealed-in-human-recipients-of-conserved-region-t-cell-vaccines
#7
Nicola Borthwick, Zhansong Lin, Tomohiro Akahoshi, Anuska Llano, Sandra Silva-Arrieta, Tina Ahmed, Lucy Dorrell, Christian Brander, Hayato Murakoshi, Masafumi Takiguchi, Tomáš Hanke
BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8+ T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28448542/diminished-plasma-levels-of-common-%C3%AE-chain-cytokines-in-pulmonary-tuberculosis-and-reversal-following-treatment
#8
Nathella Pavan Kumar, Vaithilingam V Banurekha, Dina Nair, Subash Babu
BACKGROUND: The immune response to tuberculosis (TB) is T cell dependent. T cells are the major facilitators of protection and effector functions with CD4+ T cells being the most important players, followed by CD8+ T cells. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 play a vital role in peripheral T cell growth and survival. However, the role of common γ-chain cytokines in pulmonary TB (PTB) is poorly understood. AIM AND METHODS: To examine the association of circulating common γ-chain cytokines with TB disease or infection, we examined the systemic levels of IL-2, IL-7, IL-15, and IL-21 in individuals with PTB, latent TB (LTB) or no TB infection (NTB)...
2017: PloS One
https://www.readbyqxmd.com/read/28448529/a-genome-wide-analysis-of-the-rna-guided-silencing-pathway-in-coffee-reveals-insights-into-its-regulatory-mechanisms
#9
Christiane Noronha Fernandes-Brum, Pâmela Marinho Rezende, Thales Henrique Cherubino Ribeiro, Raphael Ricon de Oliveira, Thaís Cunha de Sousa Cardoso, Laurence Rodrigues do Amaral, Matheus de Souza Gomes, Antonio Chalfun-Junior
microRNAs (miRNAs) are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs) are derived from double-stranded RNA (dsRNA) or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL) in processing the smallRNAs (sRNAs) and ARGONAUTE (AGO) as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR), Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover...
2017: PloS One
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#10
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28448060/small-rna-transfection-in-primary-human-th17-cells-by-next-generation-electroporation
#11
Misty M Montoya, K Mark Ansel
CD4(+) T cells can differentiate into several subsets of effector T helper cells depending on the surrounding cytokine milieu. Th17 cells can be generated from naïve CD4(+) T cells in vitro by activating them in the presence of the polarizing cytokines IL-1β, IL-6, IL-23, and TGFβ. Th17 cells orchestrate immunity against extracellular bacteria and fungi, but their aberrant activity has also been associated with several autoimmune and inflammatory diseases. Th17 cells are identified by the chemokine receptor CCR6 and defined by their master transcription factor, RORγt, and characteristic effector cytokine, IL-17A...
April 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28448047/a-syngeneic-mouse-model-of-metastatic-renal-cell-carcinoma-for-quantitative-and-longitudinal-assessment-of-preclinical-therapies
#12
Katherine A Murphy, Britnie R James, Andrew Wilber, Thomas S Griffith
Renal cell carcinoma (RCC) affects > 60,000 people in the United States annually, and ~ 30% of RCC patients have multiple metastases at the time of diagnosis. Metastatic RCC (mRCC) is incurable, with a median survival time of only 18 months. Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)-2) induce durable responses in a fraction of mRCC patients, and multikinase inhibitors (e.g., sunitinib or sorafenib) or anti-VEGF receptor monoclonal antibodies (mAb) are largely palliative, as complete remissions are rare...
April 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446911/the-immune-response-against-acinetobacter-baumannii-an-emerging-pathogen-in-nosocomial-infections
#13
REVIEW
María Guadalupe García-Patiño, Rodolfo García-Contreras, Paula Licona-Limón
Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective therapies against A. baumannii it is crucial to understand the basis of host-bacterium interactions, especially those concerning the immune response of the host...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28446867/response-properties-of-motor-equivalence-neurons-of-the-primate-premotor-cortex
#14
Eleftherios Neromyliotis, A K Moschovakis
To study the response properties of cells that could participate in eye-hand coordination we trained two macaque monkeys to perform center-out saccades and pointing movements with their right or left forelimb toward visual targets presented on a video display. We analyzed the phasic movement related discharges of neurons of the periarcuate cortex that fire before and during saccades and movements of the hand whether accompanied by movements of the other effector or not. Because such cells could encode an abstract form of the desired displacement vector without regard to the effector that would execute the movement we refer to such cells as motor equivalence neurons (Meq)...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28446680/non-structural-protein-l-species-specificity-supports-a-mouse-origin-for-vilyuisk-human-encephalitis-virus
#15
Melissa Drappier, Fred R Opperdoes, Thomas Michiels
Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is from human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the non-structural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. Using co-immunoprecipitation and functional RNase L assays, the species-specificity of RNase L antagonism was tested for L* from a mouse (DA) and a rat (RTV-1) TMEV strain as well as for VHEV...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446640/ref-1-ape1-as-transcriptional-regulator-and-novel-therapeutic-target-in-pediatric-t-cell-leukemia
#16
Jixin Ding, Melissa L Fishel, April M Reed, Erin McAdams, Magdalena Czader, Angelo A Cardoso, Mark R Kelley
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28446615/proliferation-of-pd-1-cd8-t-cells-in-peripheral-blood-after-pd-1-targeted-therapy-in-lung-cancer-patients
#17
Alice O Kamphorst, Rathi N Pillai, Shu Yang, Tahseen H Nasti, Rama S Akondy, Andreas Wieland, Gabriel L Sica, Ke Yu, Lydia Koenig, Nikita T Patel, Madhusmita Behera, Hong Wu, Megan McCausland, Zhengjia Chen, Chao Zhang, Fadlo R Khuri, Taofeek K Owonikoko, Rafi Ahmed, Suresh S Ramalingam
Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved...
April 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#18
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28446142/differences-in-peripheral-myelin-antigen-specific-t-cell-responses-and-t-memory-subsets-in-atypical-versus-typical-cidp
#19
M Staudt, J M Diederich, C Meisel, A Meisel, J Klehmet
BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is presented by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer from typical CIDP and show better therapy response than atypical variants. The goal of our study was to search for cellular immunological differences in typical versus atypical CIDP in comparison to controls. METHODS: We evaluated 26 (9 typical, 17 atypical) patients with mainly active-unstable CIDP using clinical and immunological examinations (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age-matched controls (HC)...
April 26, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28446061/signaling-by-antibodies-recent-progress
#20
Stylianos Bournazos, Taia T Wang, Rony Dahan, Jad Maamary, Jeffrey V Ravetch
IgG antibodies mediate a diversity of immune functions by coupling of antigen specificity through the Fab domain to signal transduction via Fc-Fc receptor interactions. Indeed, balanced IgG signaling through type I and type II Fc receptors is required for the control of proinflammatory, anti-inflammatory, and immunomodulatory processes. In this review, we discuss the mechanisms that govern IgG-Fc receptor interactions, highlighting the diversity of Fc receptor-mediated effector functions that regulate immunity and inflammation as well as determine susceptibility to infection and autoimmunity and responsiveness to antibody-based therapeutics and vaccines...
April 26, 2017: Annual Review of Immunology
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