Read by QxMD icon Read


Thomas H Segall-Shapiro, Eduardo D Sontag, Christopher A Voigt
The internal environment of growing cells is variable and dynamic, making it difficult to introduce reliable parts, such as promoters, for genetic engineering. Here, we applied control-theoretic ideas to design promoters that maintained constant levels of expression at any copy number. Theory predicts that independence to copy number can be achieved by using an incoherent feedforward loop (iFFL) if the negative regulation is perfectly non-cooperative. We engineered iFFLs into Escherichia coli promoters using transcription-activator-like effectors (TALEs)...
March 19, 2018: Nature Biotechnology
Mark J Bailey, Felix Broecker, Paul E Leon, Gene S Tan
Antibodies play a crucial role in coupling the innate and adaptive immune responses against viral pathogens through their antigen binding domains and Fc-regions. Here, we describe how to measure the activation of Fc effector functions by monoclonal antibodies targeting the influenza virus hemagglutinin with the use of a genetically engineered Jurkat cell line expressing an activating type 1 Fc-FcγR. Using this method, the contribution of specific Fc-FcγR interactions conferred by immunoglobulins can be determined using an in vitro assay...
February 23, 2018: Journal of Visualized Experiments: JoVE
Zhijuan Qiu, Brian S Sheridan
The intestinal immune system plays an essential role in maintaining the barrier function of the gastrointestinal tract by generating tolerant responses to dietary antigens and commensal bacteria while mounting effective immune responses to enteropathogenic microbes. In addition, it has become clear that local intestinal immunity has a profound impact on distant and systemic immunity. Therefore, it is important to study how an intestinal immune response is induced and what the immunologic outcome of the response is...
February 28, 2018: Journal of Visualized Experiments: JoVE
Nikolaos G Frangogiannis
Inflammation plays a crucial role in cardiac repair, but may also extend ischemic injury and contribute to post-infarction remodeling. This review manuscript discusses recent advances in our understanding of the cell biology of the post-infarction inflammatory response. Recently published studies demonstrated that the functional repertoire of inflammatory and reparative cells may extend beyond the roles suggested by traditional teachings. Neutrophils may play an important role in cardiac repair by driving macrophages toward a reparative phenotype...
February 2018: Current Opinion in Physiology
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
A Leoni Swart, Christopher F Harrison, Ludwig Eichinger, Michael Steinert, Hubert Hilbi
Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella -containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of "effector" proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit...
2018: Frontiers in Cellular and Infection Microbiology
Dong Gao, Yongguang Cai, Yanyuan Chen, Wang Li, Chih-Chang Wei, Xiaoling Luo, Yuhuan Wang
Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells...
April 2018: Oncology Letters
Jacob D Estes, Roger LeGrand, Constantinos Petrovas
Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens...
2018: Frontiers in Immunology
David Lopez, Sébastien Ribeiro, Philippe Label, Boris Fumanal, Jean-Stéphane Venisse, Annegret Kohler, Ricardo R de Oliveira, Kurt Labutti, Anna Lipzen, Kathleen Lail, Diane Bauer, Robin A Ohm, Kerrie W Barry, Joseph Spatafora, Igor V Grigoriev, Francis M Martin, Valérie Pujade-Renaud
Corynespora cassiicola is an Ascomycetes fungus with a broad host range and diverse life styles. Mostly known as a necrotrophic plant pathogen, it has also been associated with rare cases of human infection. In the rubber tree, this fungus causes the Corynespora leaf fall (CLF) disease, which increasingly affects natural rubber production in Asia and Africa. It has also been found as an endophyte in South American rubber plantations where no CLF outbreak has yet occurred. The C. cassiicola species is genetically highly diverse, but no clear relationship has been evidenced between phylogenetic lineage and pathogenicity...
2018: Frontiers in Microbiology
Jing Yang, Lin Liu, Yunfen Wang, Chunmei Wang, Jinlu Yan, Yanqin Liu, Changmi Wang, Chengyun Li
Background: BAS1 is biotrophy-associated secreted protein of rice blast strain ( Magnaporthe oryzae ). In order to study the effect of BAS1 on virulence of rice blast strain, we characterized function of BAS1 using a purified prokaryotic expression product of BAS1 and its overexpression strain. Results: Our results showed in vitro the purified expression product caused rapid callose deposition and ROS production in rice leaves and calli, indicated it triggered transient basal defense. When the purified expression product of BAS1 was sprayed onto rice leaves, and 24 h later the leaves were inoculated with blast strain, the results showed the size and number of lesions, on purified BAS1 product-pretreated leaves of the Lijiangxintuanheigu (LTH) challenged with blast strain, was higher than those in BAS1-untreated leaves directly challenged with the same strain, which suggested the defense response trigged by BAS1 can be overcome by other effectors of the fungus...
December 2017: Saudi Journal of Biological Sciences
Qiang Zuo, Jing Liu, Liping Huang, Yifei Qin, Teresa Hawley, Claire Seo, Glenn Merlino, Yanlin Yu
Multiple genetic mutations within melanoma not only cause lesion-specific responses to targeted therapy but also alter the molecular route of resistance to that therapy. Inactivation of PTEN occurs in up to 30% of melanomas, frequently with a concurrent activating BRAF mutation. PTEN loss regulates both acquired and intrinsic drug resistance. Here we show that AXL/AKT axis mediated-resistance to BRAF inhibitor (BRAFi) depends upon PTEN status in melanoma. Hyperactivation of both ERK and AKT pathways was associated with BRAFi resistance in melanoma with wildtype PTEN...
March 19, 2018: Oncogene
Winston X Yan, Shaorong Chong, Huaibin Zhang, Kira S Makarova, Eugene V Koonin, David R Cheng, David A Scott
Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c...
March 9, 2018: Molecular Cell
Silvana Konermann, Peter Lotfy, Nicholas J Brideau, Jennifer Oki, Maxim N Shokhirev, Patrick D Hsu
Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity. Here, we analyzed prokaryotic genome and metagenome sequences to identify an uncharacterized family of RNA-guided, RNA-targeting CRISPR systems that we classify as type VI-D. Biochemical characterization and protein engineering of seven distinct orthologs generated a ribonuclease effector derived from Ruminococcus flavefaciens XPD3002 (CasRx) with robust activity in human cells. CasRx-mediated knockdown exhibits high efficiency and specificity relative to RNA interference across diverse endogenous transcripts...
March 8, 2018: Cell
Kai Cao, Stephen W G Tait
Apoptotic cell death serves as an important tumor suppressor mechanism at multiple steps during cancer progression. Equally, engagement of apoptosis represents a potent therapeutic effector mechanism. Nevertheless, the role of apoptosis in cancer may be more complex than previously thought. Indeed, various studies have found that apoptosis signaling also has oncogenic potential. In this review, we discuss how apoptosis can promote cancer and how these effects might be targeted to optimize apoptosis-inducing anticancer therapy...
2018: International Review of Cell and Molecular Biology
Maria Bottermann, Leo C James
Innate immunity is traditionally thought of as the first line of defense against pathogens that enter the body. It is typically characterized as a rather weak defense mechanism, designed to restrict pathogen replication until the adaptive immune response generates a tailored response and eliminates the infectious agent. However, intensive research in recent years has resulted in better understanding of innate immunity as well as the discovery of many effector proteins, revealing its numerous powerful mechanisms to defend the host...
2018: Advances in Virus Research
Tian Liu, Dongliang Zhang, Yuan Zhang, Xiangsheng Xu, Bo Zhou, Liang Fang, Yun Zhang, Yingjun Su, Boquan Jin, Ran Zhuang, Shuzhong Guo
BACKGROUND/AIMS: Regulatory T cells (Tregs) play key roles in maintaining peripheral tolerance and preventing autoimmune disease. Treg modulation could be helpful in treating malignancies, autoimmune disease, and allergies, as well as to facilitate organ transplantation. Signals transduced by co-stimulatory molecules are essential for Treg differentiation, homeostasis, and function. One well-known active receptor, CD226, also known as DNAM-1 or PTA1, is an adhesion molecule that interacts primarily with CD155 and is involved in Treg differentiation and immune tolerance to transplanted tissue...
March 13, 2018: Cellular Physiology and Biochemistry
Heather L Howie, Xiaohong Wang, Linda Kapp, Jenna N Lebedev, James C Zimring
There are four subtypes of human IgG with different effector functions. Quantifying the relative amount of each IgG subtype is important for laboratory diagnosis in multiple settings. However, in an evolving landscape of the appreciation of human variability and the need for precision/personalised laboratory diagnosis, it has also been shown that there are numerous natural variants of IgG subtypes, with at least 29 having been described. It has recently been reported that commercially available polyclonal antisera to IgG3 cross react with variants of other IgG subtypes, while available monoclonal anti-IgG3 have a blind-spot for the IgG3-04 variant...
March 17, 2018: Journal of Clinical Pathology
Doreen Baumann, Helen Salia, Lilo Greune, Stephanie Norkowski, Britta Körner, Zina M Uckeley, Gad Frankel, Marianne Guenot, Christian Rüter, M Alexander Schmidt
Enteropathogenic Escherichia coli (EPEC) subvert host cell signaling pathways by injecting effector proteins via a Type 3 Secretion System (T3SS). The T3SS-dependent EspB protein is a multi-functional effector protein, which contributes to adherence and translocator pore formation and after injection exhibits several intracellular activities. In addition, EspB is also secreted into the environment. Effects of secreted EspB have not been reported thus far. As a surrogate for secreted EspB we employed recombinant EspB (rEspB) derived from the prototype EPEC strain E2348/69 and investigated the interactions of the purified protein with different human epithelial and immune cells including monocytic THP-1 cells, macrophages, dendritic cells, U-937, epithelial T84, Caco-2, and HeLa cells...
March 12, 2018: International Journal of Medical Microbiology: IJMM
Yanfeng Tuo, Xing Song, Yinglong Song, Wenwen Liu, Yu Tang, Yuan Gao, Shujuan Jiang, Fang Qian, Guangqing Mu
Probiotics can be screened according to their abilities to inhibit pathogen adhesion and inhibit the production of pro-inflammatory cytokines. Eleven Lactobacillus strains isolated from traditional fermented dairy foods in Xinjiang, China, were studied for their potential to inhibit adhesion of Escherichia coli to intestinal epithelial cells and to inhibit E. coli-induced production of interleukin (IL)-8 by intestinal epithelial cells. The results showed that the 11 strains could inhibit adhesion of E. coli to Caco-2 cell monolayers and inhibit the induction of IL-8 production by E...
March 14, 2018: Journal of Dairy Science
Julia Brenmoehl, Daniela Ohde, Elisa Wirthgen, Andreas Hoeflich
Cytokines are required for normal growth and development of the mammary gland and TGF-β prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential...
January 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"