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https://www.readbyqxmd.com/read/27936513/probing-the-structural-dynamics-of-the-crispr-cas9-rna-guided-dna-cleavage-system-by-coarse-grained-modeling
#1
Wenjun Zheng
In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936512/genome-editing-of-the-disease-susceptibility-gene-cslob1-in-citrus-confers-resistance-to-citrus-canker
#2
Hongge Jia, Yunzen Zhang, Vladimir Orbovic, Jin Xu, Frank White, Jeffrey Jones, Nian Wang
Citrus is a highly valued tree crop worldwide, while, at the same time, citrus production faces many biotic challenges, including bacterial canker and Huanglongbing (HLB). Breeding for disease resistant varieties is the most efficient and sustainable approach to control plant diseases. Traditional breeding of citrus varieties is challenging due to multiple limitations, including polyploidy, polyembryony, extended juvenility, and long crossing cycles. Targeted genome editing technology has the potential to shorten varietal development for some traits, including disease resistance...
December 9, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27936496/simultaneous-stimulation-of-the-sbpase-fbp-aldolase-and-the-photorespiratory-gdc-h-protein-increases-co2-assimilation-vegetative-biomass-and-seed-yield-in-arabidopsis
#3
Andrew J Simkin, Patricia E Lopez-Calcagno, Philip A Davey, Lauren R Headland, Tracy Lawson, Stefan Timm, Hermann Bauwe, Christine A Raines
In this paper we have altered the levels of three different enzymes involved in the Calvin Benson cycle and photorespiratory pathway. We have generated transgenic Arabidopsis plants with altered combinations of sedoheptulose 1,7-bisphosphatase (SBPase), fructose 1,6-bisphophate aldolase (FBPA) and the glycine decarboxylase H-protein (GDC-H) gene identified as targets to improve photosynthesis based on previous studies. Here, we show that increasing the levels of the three corresponding proteins, either independently or in combination, significantly increases the quantum efficiency of PSII...
December 9, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27936493/new-additions-to-the-cluspro-server-motivated-by-capri
#4
Sandor Vajda, Christine Yueh, Dmitri Beglov, Tanggis Bohnuud, Scott E Mottarella, Bing Xia, David R Hall, Dima Kozakov
The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for Small Angle X-ray Scattering (SAXS) data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936492/lncrna-a-versatile-regulator-of-the-nf-%C3%AE%C2%BAb-signaling-circuit
#5
REVIEW
Xiaohua Mao, Zhenyi Su, Adnan K Mookhtiar
The Nuclear Factor-κB (NF-κB) family of transcription factors play an essential role for the regulation of inflammatory responses, immune function and malignant transformation. Aberrant activity of this signaling pathway may lead to inflammation, autoimmune diseases and oncogenesis. Over the last two decades great progress has been made in the understanding of NF-κB activation and how the response is counteracted for maintaining tissue homeostasis. Therapeutic targeting of this pathway has largely remained ineffective due to the widespread role of this vital pathway and the lack of specificity of the therapies currently available...
December 9, 2016: Immunology
https://www.readbyqxmd.com/read/27936486/microrna-4656-is-a-prognostic-factor-and-tumor-suppressor-in-human-pancreatic-through-downstream-tareget-of-trka
#6
Xianglong Tan, Jinyong Lv, Guodong Zhao, Zhiming Zhao, Chenggang Li, Yong Xu, Minggen Hu
BACKGROUND: In this study, we investigated the expression profile and functional mechanism of microRNA-4656 in human pancreatic cancer (PC). METHODS: MiR-4656 expression in PC tumors was examined by qRT-PCR in 134 patients. Associations between tumorous miR-4656 expression and patient's clinicopathological parameters and overall survival were analyzed. MiR-4656 expression was also examined in PC in vitro cell lines. In Capan-1 and AsPC-1 PC cells, lentivirus-induced miR-4656 overexpression or downregulation was applied to investigate its functional regulations on PC in vitro proliferation and invasion, and in vivo transplant growth...
December 9, 2016: Journal of Gene Medicine
https://www.readbyqxmd.com/read/27936466/dpp4-cd26-overexpression-in-urothelial-carcinoma-confers-an-independent-prognostic-impact-and-correlates-with-intrinsic-biological-aggressiveness
#7
Peir-In Liang, Bi-Wen Yeh, Wei-Ming Li, Ti-Chun Chan, I-Wei Chang, Chun-Nung Huang, Ching-Chia Li, Hung-Lung Ke, Hsin-Chih Yeh, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC) is common cancer worldwide. The molecular aberrations regarding tumor progression remain unclear. Pericellular proteolysis is crucial in tumorigenesis, but its significance is unexplored in UC. By data mining the datasets in Gene Expression Omnibus, specifically focus on the proteolysis pathway, and followed by a preliminary validation in a pilot batch of tumor samples, we identified that the upregulation of dipeptidyl peptidase 4 (DPP4) was most significantly associated with clinical aggressiveness of UCs...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#8
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936459/mir-23a-inhibited-il-17-mediated-proinflammatory-mediators-expression-via-targeting-ikk%C3%AE-in-articular-chondrocytes
#9
Junzheng Hu, Chenjun Zhai, Jiaojiao Hu, Zeng Li, Hao Fei, Zhen Wang, Weimin Fan
The inflammatory cytokine interleukin 17 (IL-17) is an important contributor of rheumatoid arthritis (RA) chronicity. Although several microRNAs (miRNAs) have been shown to regulate RA pathogenesis, the function of miRNAs in articular chondrocytes during rheumatoid arthritis pathogenesis is unclear. Here we showed that miR-23a was downregulated in articular cartilage tissues from rheumatoid arthritis patients. MiR-23a suppressed IL-17 inflammatory cytokine-induced NF-κB activation and several proinflammatory mediators expression, such as cytokine IL-6, chemokine MCP-1, and matrix metalloproteinase MMP-3 in articular chondrocytes...
December 6, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27936456/1%C3%AE-25-dihydroxyvitamin-d-inhibits-de-novo-fatty-acid-synthesis-and-lipid-accumulation-in-metastatic-breast-cancer-cells-through-down-regulation-of-pyruvate-carboxylase
#10
Tomasz Wilmanski, Kimberly Buhman, Shawn S Donkin, John R Burgess, Dorothy Teegarden
Both increased de novo fatty acid synthesis and higher neutral lipid accumulation are a common phenotype observed in aggressive breast cancer cells, making lipid metabolism a promising target for breast cancer prevention. In the present studies, we demonstrate a novel effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)₂D) on lipid metabolism in malignant breast epithelial cells. Treatment of MCF10CA1a breast epithelial cells with 1,25(OH)₂D (10 nM) for 5 and 7 days decreased the level of triacylglycerol, the most abundant form of neutral lipids, by 20%(±3...
December 1, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27936446/design-synthesis-and-evaluation-of-4-aminoquinoline-purine-hybrids-as-potential-antiplasmodial-agents
#11
P Linga Reddy, Shabana I Khan, Prija Ponnan, Mohit Tripathi, Diwan S Rawat
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P...
December 1, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27936442/label-free-colorimetric-detection-of-cancer-related-gene-based-on-two-step-amplification-of-molecular-machine
#12
Huo Xu, Dong Wu, Chen-Qiao Li, Zheng Lu, Xiao-Yun Liao, Jie Huang, Zai-Sheng Wu
Highly sensitive detection of K-ras gene is of great significance in biomedical research and clinical diagnosis. Here, we developed a colorimetric biosensing system for the detection of proto-oncogene K-ras based on enhanced amplification effect of DNA molecular machine, where dual isothermal circular strand-displacement amplification (D-SDA) occurs on two arms in one-to-one correspondence. Specifically, we designed a primer-locked hairpin probe (HP) and a primer-contained linear polymerization template (PPT)...
December 2, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27936436/spectroscopic-single-crystal-x-ray-hirshfeld-in-vitro-and-in-silico-biological-evaluation-of-a-new-series-of-potent-thiazole-nucleus-integrated-with-pyrazoline-scaffolds
#13
Vinutha V Salian, Badiadka Narayana, Balladka K Sarojini, Madan S Kumar, Govinahalli S Nagananda, Kullaiah Byrappa, Avinash K Kudva
In the present study, the spectroscopic characterization of a new series of substituted thiazole linked pyrazoline scaffolds 4a-l was performed. The formation of 4a-l from the intermediate 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2 and substituted 2-bromo-1-phenylethanone 3a-l was evidenced through the changes in FTIR, (1)H NMR, (13)C NMR, LCMS data. The X-ray diffraction studies revealed that compound 2 and 4g crystallized in monoclinic crystal system with P21/n space group...
November 28, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27936416/antigen-recognition-triggered-drug-delivery-mediated-by-nanocapsule-functionalized-cytotoxic-t-cells
#14
R Brad Jones, Stephanie Mueller, Sudha Kumari, Vlad Vrbanac, Shy Genel, Andrew M Tager, Todd M Allen, Bruce D Walker, Darrell J Irvine
Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27936412/contribution-of-cellular-autolysis-to-tissular-functions-during-plant-development
#15
REVIEW
Sacha Escamez, Hannele Tuominen
Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it appears biologically meaningful to distinguish between the modules of PCD and autolysis during plant development...
December 6, 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/27936410/body-image-and-emotional-distress-in-newly-diagnosed-cancer-patients-the-mediating-role-of-dysfunctional-attitudes-and-rumination
#16
Jianlin Liu, Chao Xu Peh, Rathi Mahendran
Body image concerns (BIC) has been reported to be associated with emotional distress for cancers across various sites. This study sought to examine two cognitive vulnerability mechanisms: dysfunctional attitudes and rumination, and their combined effects on the relationship between BIC and emotional distress in newly diagnosed Asian cancer patients. Participants were 221 newly diagnosed adult cancer patients who were assessed on BIC, rumination, dysfunctional attitudes, and emotional distress. Path analysis was used to examine the hypothesized mediation model...
December 6, 2016: Body Image
https://www.readbyqxmd.com/read/27936408/biased-mu-opioid-receptor-ligands-a-promising-new-generation-of-pain-therapeutics
#17
REVIEW
Edward R Siuda, Richard Carr, David H Rominger, Jonathan D Violin
Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events...
December 6, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27936398/microrna138-regulates-keratin-17-protein-expression-to-affect-hacat-cell-proliferation-and-apoptosis-by-targeting-htert-in-psoriasis-vulgaris
#18
Shi-Jun Feng, Rui-Qi Chu, Jing Ma, Zheng-Xiang Wang, Guang-Jing Zhang, Xiu-Fang Yang, Zhi Song, Yun-Yi Ma
The purpose of this study is to explore the how microRNA-138 (miR-138) affects the expression of keratin 17 (K17) and psoriasis development. Twenty-eight skin lesions from patients with psoriasis vulgaris and twenty-four normal skin tissues from healthy controls were collected. The HaCaT cells were assigned into blank, negative control (NC), miR-138 mimic, miR-138 inhibitor, hTERT siRNA and miR-138 inhibitor+hTERT siRNA groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the miR-138 expression...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27936379/clinical-and-epidemiological-characteristics-associated-with-unfavorable-tuberculosis-treatment-outcomes-in-tb-hiv-co-infected-patients-in-brazil-a-hierarchical-polytomous-analysis
#19
Thiago Nascimento do Prado, Jayant V Rajan, Angélica Espinosa Miranda, Elias Dos Santos Dias, Lorrayne Beliqui Cosme, Lia Gonçalves Possuelo, Mauro N Sanchez, Jonathan E Golub, Lee W Riley, Ethel Leonor Maciel
BACKGROUND: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. METHODS: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB)...
December 6, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27936376/peer-network-counseling-as-brief-treatment-for-urban-adolescent-heavy-cannabis-users
#20
Michael J Mason, Roy Sabo, Nikola M Zaharakis
OBJECTIVE: A small body of evidence supports targeting adolescents who are heavy users of cannabis with brief interventions, yet more research is needed to confirm the effectiveness of these studies. We conducted a secondary analysis of our Peer Network Counseling (PNC) study (Mason et al., 2015), focusing on 46 adolescents of the sample of 119 who reported heavy cannabis use at baseline. METHOD: Urban adolescents (91% African American) presenting for primary health care were randomized to intervention or control conditions and followed for 6 months...
January 2017: Journal of Studies on Alcohol and Drugs
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