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https://www.readbyqxmd.com/read/29458177/colorimetric-detection-of-microrna-based-on-dnazyme-and-nuclease-assisted-catalytic-hairpin-assembly-signal-amplification
#1
Hongmei Zhang, Kuiyu Wang, Shengjun Bu, Zhongyi Li, Chuanjing Ju, Jiayu Wan
Accurate and quantitative analysis of microRNA (miRNA) expression is critical for the diagnostics and theranostics of a disease. Herein, a proof-of-concept of a colorimetric horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) biosensor for miRNA assay based on nuclease-assisted catalytic hairpin assembly (CHA) signal amplification was demonstrated. Duplex-specific nuclease (DSN) was employed to cleave the single-stranded DNA (ssDNA) chimeric probe (CP) on the magnetic bead (MB) surface via hybridization of the CP and target miRNA...
February 16, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29457714/selective-recognition-of-rna-substrates-by-adar-deaminase-domains
#2
Yuru Wang, SeHee Park, Peter A Beal
Adenosine deamination is one of the most prevalent post-transcriptional modifications in mRNA and is catalyzed by ADAR1 and ADAR2 in humans. ADAR1 and ADAR2 have different substrate selectivity, which is believed to mainly originate from the proteins' deaminase domains (hADAR1d and hADAR2d, respectively). RNA-seq of the S. cerevisiae transcriptome subjected to ADAR-catalyzed RNA editing identified substrates with common secondary structure features preferentially edited by hADAR1d over hADAR2d. The relatively small size and efficient reaction of one of these substrates suggested it could be useful for further study of the hADAR1d reaction...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29454339/a-structural-preview-of-aquaporin-8-via-homology-modeling-of-seven-vertebrate-isoforms
#3
Andreas Kirscht, Yonathan Sonntag, Per Kjellbom, Urban Johanson
BACKGROUND: Aquaporins (AQPs) facilitate the passage of small neutral polar molecules across membranes of the cell. In animals there are four distinct AQP subfamilies, whereof AQP8 homologues constitute one of the smallest subfamilies with just one member in man. AQP8 conducts water, ammonia, urea, glycerol and H2 O2 through various membranes of animal cells. This passive channel has been connected to a number of phenomena, such as volume change of mitochondria, ammonia neurotoxicity, and mitochondrial dysfunction related to oxidative stress...
February 17, 2018: BMC Structural Biology
https://www.readbyqxmd.com/read/29454308/the-unique-evolutionary-pattern-of-the-hydroxyproline-rich-glycoproteins-superfamily-in-chinese-white-pear-pyrus-bretschneideri
#4
Huijun Jiao, Xing Liu, Shuguang Sun, Peng Wang, Xin Qiao, Jiaming Li, Chao Tang, Juyou Wu, Shaoling Zhang, Shutian Tao
BACKGROUND: The hydroxyproline-rich glycoprotein (HRGP) superfamily, comprising three families (arabinogalactan-proteins, AGPs; extensins, EXTs; proline-rich proteins, PRPs), is a class of proline-rich proteins that exhibit high diversity and are involved in many aspects of plant biology. RESULTS: In this study, 838 HRGPs were identified from Chinese white pear (Pyrus bretschneideri) by searching for biased amino acid composition and conserved motifs. 405 HRGPs were derived from whole genome duplication (WGD) events which is suggested to be the major force of driving HRGPs expansion and the recent WGD event shared by apple and pear generated most duplicated HRGPs in pear...
February 17, 2018: BMC Plant Biology
https://www.readbyqxmd.com/read/29453518/chimeric-antigen-receptors-with-human-scfvs-preferentially-induce-t-cell-anti-tumor-activity-against-tumors-with-high-b7h6-expression
#5
Albert T Gacerez, Casey K Hua, Margaret E Ackerman, Charles L Sentman
B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29453239/a-next-generation-chimeric-antigen-receptor-induces-jak-stat-signaling
#6
(no author information available yet)
CAR-T cells designed to activate JAK-STAT signaling show enhanced persistence and antitumor activity.
February 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29453226/modeling-the-human-bone-marrow-niche-in-mice-from-host-bone-marrow-engraftment-to-bioengineering-approaches
#7
REVIEW
Ander Abarrategi, Syed A Mian, Diana Passaro, Kevin Rouault-Pierre, William Grey, Dominique Bonnet
Xenotransplantation of patient-derived samples in mouse models has been instrumental in depicting the role of hematopoietic stem and progenitor cells in the establishment as well as progression of hematological malignancies. The foundations for this field of research have been based on the development of immunodeficient mouse models, which provide normal and malignant human hematopoietic cells with a supportive microenvironment. Immunosuppressed and genetically modified mice expressing human growth factors were key milestones in patient-derived xenograft (PDX) models, highlighting the importance of developing humanized microenvironments...
February 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29452245/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-using-non-first-degree-related-donors
#8
Hany Elmariah, Yvette L Kasamon, Marianna Zahurak, Karen W Macfarlane, Noah Tucker, Gary L Rosner, Javier Bolaños-Meade, Ephraim J Fuchs, Nina Wagner-Johnston, Lode J Swinnen, Carol Ann Huff, William H Matsui, Douglas E Gladstone, Shannon R McCurdy, Ivan Borrello, Christian B Gocke, Satish Shanbhag, Kenneth R Cooke, Syed Abbas Ali, Robert A Brodsky, Amy E DeZern, Leo Luznik, Richard J Jones, Richard F Ambinder
Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non-first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age 56 years) with hematologic malignancies who underwent NMA haplo T-cell replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%)...
February 13, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29451276/tisagenlecleucel-an-approved-anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-leukemia
#9
Y Liu, X Chen, W Han, Y Zhang
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients. Conventional standard therapies for B-ALL have high failure rates, thus developing new therapies is crucial for patients with B-ALL...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29449556/cd1d-dependent-immune-suppression-mediated-by-regulatory-b-cells-through-modulations-of-inkt-cells
#10
K Oleinika, E C Rosser, D E Matei, K Nistala, A Bosma, I Drozdov, C Mauri
Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis...
February 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29448937/engineering-chimeric-antigen-receptor-t-cells-for-cancer-treatment
#11
REVIEW
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29448044/safety-evaluation-of-a-human-chimeric-monoclonal-antibody-that-recognizes-the-extracellular-loop-domain-of-claudin-2
#12
Yosuke Hashimoto, Tomoyuki Hata, Minoru Tada, Manami Iida, Akihiro Watari, Yoshiaki Okada, Takefumi Doi, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
Claudin-2 (CLDN-2), a pore-forming tight-junction protein with a tetra-transmembrane domain, is involved in carcinogenesis and the metastasis of some cancers. Although CLDN-2 is highly expressed in the tight junctions of the liver and kidney, whether CLDN-2 is a safe target for cancer therapy remains unknown. We recently generated a rat monoclonal antibody (mAb, clone 1A2) that recognizes the extracellular domains of human and mouse CLDN-2. Here, we investigated the safety of CLDN-2-targeted cancer therapy by using 1A2 as a model therapeutic antibody...
February 12, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29447672/formulation-of-dna-chimera-templates-effects-on-emission-behavior-of-silver-nanoclusters-and-sensing
#13
Shi Ting Lee, David Beaumont, Xiao Di Su, Kasturi Muthoosamy, Siu Yee New
Single strand DNA (ssDNA) chimeras consisting of a silver nanoclusters-nucleating sequence (NC) and an aptamer are widely employed to synthesize functional silver nanoclusters (AgNCs) for sensing purpose. Despite its simplicity, this chimeric-templated AgNCs often leads to undesirable turn-off effect, which may suffer from false positive signals caused by interference. In our effort to elucidate how the relative position of NC and aptamer affects the fluorescence behavior and sensing performance, we systematically formulated these NC and aptamer regions at different position in a DNA chimera...
June 20, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29447156/west-nile-and-st-louis-encephalitis-viral-genetic-determinants-of-avian-host-competence
#14
Payal D Maharaj, Angela M Bosco-Lauth, Stanley A Langevin, Michael Anishchenko, Richard A Bowen, William K Reisen, Aaron C Brault
West Nile virus (WNV) and St. Louis encephalitis (SLEV) virus are enzootically maintained in North America in cycles involving the same mosquito vectors and similar avian hosts. However, these viruses exhibit dissimilar viremia and virulence phenotypes in birds: WNV is associated with high magnitude viremias that can result in mortality in certain species such as American crows (AMCRs, Corvus brachyrhynchos) whereas SLEV infection yields lower viremias that have not been associated with avian mortality. Cross-neutralization of these viruses in avian sera has been proposed to explain the reduced circulation of SLEV since the introduction of WNV in North America; however, in 2015, both viruses were the etiologic agents of concurrent human encephalitis outbreaks in Arizona, indicating the need to re-evaluate host factors and cross-neutralization responses as factors potentially affecting viral co-circulation...
February 15, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29446998/considerations-for-clinical-review-of-cellular-therapy-products-perspectives-of-the-china-food-and-drug-administration-center-for-drug-evaluation
#15
Yantong Liu, Chenyang Zhao, Liucun Gao, Huan Yang, Ruyi He, Chenyan Gao
With increasing numbers of technical developments and clinical studies, pioneering cellular/gene therapies are now available that could cure life-threatening disease. Cellular/gene therapy products are broad-ranging and complicated, and thereby bring challenges for clinical review by regulatory agencies. This review discusses principles for the clinical review of cellular therapy products, including protection of clinical trial populations, pharmacodynamics, pharmacokinetics, dose evaluation, clinical efficacy, clinical safety, and risk-management plans...
February 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29445768/hstrpa-of-the-red-imported-fire-ant-solenopsis-invicta-functions-as-a-nocisensor-and-uncovers-the-evolutionary-plasticity-of-hstrpa-channels
#16
Xinyue Wang, Tianbang Li, Makiko Kashio, Yijuan Xu, Makoto Tominaga, Tatsuhiko Kadowaki
Solenopsis invicta , the red imported fire ant, represents one of the most devastating invasive species. To understand their sensory physiology, we identified and characterized their Hymenoptera-specific (Hs) TRPA channel, SiHsTRPA. Consistent with the sensory functions of SiHsTRPA, it is activated by heat, an electrophile, and an insect repellent. Nevertheless, SiHsTRPA does not respond to most of the honey bee ortholog (AmHsTRPA)-activating compounds. The jewel wasp ortholog (NvHsTRPA) is activated by these compounds even though it outgroups both AmHsTRPA and SiHsTRPA...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29445153/development-of-a-chimeric-zika-vaccine-using-a-licensed-live-attenuated-flavivirus-vaccine-as-backbone
#17
Xiao-Feng Li, Hao-Long Dong, Hong-Jiang Wang, Xing-Yao Huang, Ye-Feng Qiu, Xue Ji, Qing Ye, Chunfeng Li, Yang Liu, Yong-Qiang Deng, Tao Jiang, Gong Cheng, Fu-Chun Zhang, Andrew D Davidson, Ya-Jun Song, Pei-Yong Shi, Cheng-Feng Qin
The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models...
February 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29445070/development-to-term-of-sheep-embryos-reconstructed-after-inner-cell-mass-trophoblast-exchange
#18
Pasqualino Loi, Cesare Galli, Giovanna Lazzari, Kazutsugu Matsukawa, Josef Fulka Jr, Frank Goeritz, Thomas B Hildebrandt
Here we report in vitro and term development of sheep embryos after the inner cell mass (ICM) from one set of sheep blastocysts were injected into the trophoblast vesicles of another set. We also observed successful in vitro development of chimeric blastocysts made from sheep trophoblast vesicles injected with bovine ICM. First, we dissected ICMs from 35 sheep blastocysts using a stainless steel microblade and injected them into 29 re-expanded sheep trophoblastic vesicles. Of the 25 successfully micromanipulated trophoblastic vesicles, 15 (51...
February 15, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29444959/the-synaptotagmin-c2b-domain-calcium-binding-loops-modulate-the-rate-of-fusion-pore-expansion
#19
Mounir Bendahmane, Kevin P Bohannon, Mazdak M Bradberry, Tejeshwar C Rao, Michael W Schmidtke, Prabhodh S Abbineni, Nara L Chon, Sherleen Tran, Hai Lin, Edwin R Chapman, Jefferson D Knight, Arun Anantharam
In chromaffin cells, the kinetics of fusion pore expansion vary depending on which synaptotagmin isoform (Syt-1 or Syt-7) drives release. Our recent studies have shown that fusion pores of granules harboring Syt-1 expand more rapidly than those harboring Syt-7. Here, we sought to define the structural specificity of synaptotagmin action at the fusion pore by manipulating the Ca 2+ -binding C2B module. We generated a chimeric Syt-1 in which its C2B Ca 2+ -binding loops had been exchanged for those of Syt-7. Fusion pores of granules harboring a Syt-1 C2B chimera with all three Ca 2+ -binding loops of Syt-7 (Syt-1:7C2B 123 ) exhibited slower rates of fusion pore expansion and neuropeptide cargo release relative to WT Syt-1...
February 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29443792/pleural-cavity-cytokine-release-syndrome-in-cd19-directed-chimeric-antigen-receptor-modified-t-cell-therapy-a-case-report
#20
Lijuan Ding, Yongxian Hu, Kui Zhao, Guoqing Wei, Wenjun Wu, Zhao Wu, Lei Xiao, He Huang
RATIONALE: Cytokine release syndrome (CRS) is a common and potentially fatal complication of CAR-T cell therapy. However, compartment CRS is relatively rare in hematological malignancies, as well as in solid tumors. The pathogenesis and prognosis of compartment CRS are unclear and there is no standardized treatment yet. In this case report, we will introduce a patient developing pleural cavity CRS after CART19s infusion. PATIENT CONCERNS: A 28-year-old woman was admitted for evaluation of mediastinal mass...
February 2018: Medicine (Baltimore)
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