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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/27936499/the-anatomy-of-mammalian-sweet-taste-receptors
#2
Jean-Baptiste Chéron, Jérôme Golebiowski, Serge Antonczak, Sébastien Fiorucci
All sweet-tasting compounds are detected by a single G-protein coupled receptor (GPCR), the heterodimer T1R2-T1R3, for which no experimental structure is available. The sweet taste receptor is a class C GPCR, and the recently published crystallographic structures of metabotropic glutamate receptor (mGluR) 1 and 5 provide a significant step forward for understanding structure-function relationships within this family. In this article, we recapitulate more than six hundred single point site-directed mutations and available structural data to obtain a critical alignment of the sweet taste receptor sequences with respect to other class C GPCRs...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936497/pro-inflammatory-cytokine-ifn%C3%AE-and-microbiome-derived-metabolites-dictate-epigenetic-switch-between-foxp3-isoforms-in-celiac-disease-regulation-of-foxp3-isoforms-in-celiac-disease
#3
Gloria Serena, Shu Yan, Stephanie Camhi, Shilpi Patel, Rosiane S Lima, Anna Sapone, Maureen M Leonard, Rupa Mukherjee, Barbara J Nath, Karen M Lammers, Alessio Fasano
Celiac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong Th1/Th17 immune response in the small intestine. Treg cells are CD4(+) CD25(++) FOXP3(+) cells that regulate the immune response. Conversely to its counterpart, FOXP3 full length (FL), the alternatively spliced isoform FOXP3 Δ2 cannot properly down-regulate Th17 driven immune response. Since the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FOXP3 isoforms may be associated with the disease...
December 9, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27936492/lncrna-a-versatile-regulator-of-the-nf-%C3%AE%C2%BAb-signaling-circuit
#4
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/27936488/ro52-trim21-deficient-expression-and-function-in-different-subsets-of-peripheral-blood-mononuclear-cells-is-associated-with-a-pro-inflammatory-cytokine-response-in-patients-with-idiopathic-inflammatory-myopathies
#5
D Gómez-Martín, A S Galindo-Feria, A Barrera-Vargas, J Merayo-Chalico, G Juárez-Vega, J Torres-Ruiz, J Alcocer-Varela
The presence of anti-Ro52/Trim21 autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyze Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with pro-inflammatory cytokine production. We included 18 patients with recent onset IIM and 18 age and gender-matched healthy donors...
December 9, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27936487/the-evolution-of-function-within-the-nudix-homology-clan
#6
John R Srouji, Anting Xu, Annsea Park, Jack F Kirsch, Steven E Brenner
The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch-specific adenine glycosylases (A/G-specific adenine glycosylases), and non-enzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936486/microrna-4656-is-a-prognostic-factor-and-tumor-suppressor-in-human-pancreatic-through-downstream-tareget-of-trka
#7
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/27936480/treatment-of-fulminant-acute-hepatitis-b-with-nucles-t-id-analogues-is-safe-and-does-not-lead-to-secondary-chronification-of-hepatitis-b
#8
C Jochum, F Maischack, O E Anastasiou, J Verheyen, J Timm, L Bechmann, G Gerken, A Canbay
Background: Acute hepatitis B virus (HBV) infection is still a major cause of acute liver failure (ALF), necessitating a high rate of emergency liver transplantation (LTx). Acute infection is followed by high viral replication rates leading to hepatocyte death and, ultimately, ALF. The objective of treating HBV-induced ALF thus is to eliminate, or significantly suppress, HBV replication and therefore reduce cell death and support regeneration. Objective: In this retrospective study, we want to evaluate the timing, the safety, and the long-term virological outcome of this approach...
December 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27936463/virus-like-particles-displaying-h5-h7-h9-hemagglutinins-and-n1-neuraminidase-elicit-protective-immunity-to-heterologous-avian-influenza-viruses-in-chickens
#9
Peter Pushko, Irina Tretyakova, Rachmat Hidajat, Aniko Zsak, Klaudia Chrzastek, Terrence M Tumpey, Darrell R Kapczynski
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities...
December 6, 2016: Virology
https://www.readbyqxmd.com/read/27936461/pterostilbene-protects-against-myocardial-ischemia-reperfusion-injury-via-suppressing-oxidative-nitrative-stress-and-inflammatory-response
#10
Zhaoxia Yu, Shaohua Wang, Xiangyang Zhang, Ying Li, Qiang Zhao, Tao Liu
Recent studies have shown that pterostilbene (Pte) confers protection against myocardial ischemia/reperfusion injury. The oxidative/nitrative stress and inflammation induce injury after myocardial ischemia/reperfusion. The present study was designed to evaluate whether treatment with Pte attenuates oxidative/nitrative stress and inflammation in myocardial ischemia/reperfusion (MI/R). Rats were subjected to 30min of myocardial ischemia and 3h of reperfusion, and the rats were administered with vehicle or Pte...
December 6, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27936460/b-cells-present-skewed-profile-and-lose-the-function-of-supporting-t-cell-inflammation-after-roux-en-y-gastric-bypass
#11
Xiaojiang Dai, Weiguo Zhao, Junfang Zhan, Songhua Zeng, Dongzhi Ran, Hongbin Zhang, Zhigao Song, Ken H Song, Liangping Wu
Bariatric surgeries, including Roux-en-Y gastric bypass (RYGB) are currently the best treatment for obesity and obesity-related comorbidities, such as type 2 diabetes. However, the underlying mechanism of bariatric surgeries is not entirely understood. Further investigations are needed to improve the success rate and achieve sustained health benefits. Given that B cell dysregulation is a critical component of etiology in inflammatory diseases, whereas obesity and type 2 diabetes represent two major inflammatory disorders, we investigated the effect of RYGB on B cell inflammation...
December 6, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27936459/mir-23a-inhibited-il-17-mediated-proinflammatory-mediators-expression-via-targeting-ikk%C3%AE-in-articular-chondrocytes
#12
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/27936458/predictors-of-functional-disability-with-focus-on-activities-of-daily-living-a-community-based-follow-up-study-in-older-adults-in-india
#13
Aarti Nagarkar, Yashoda Kashikar
BACKGROUND: Disability in activities of daily living is a growing concern among older populations all over the world. India has one of the rapidly ageing populations and predicted burden of functional disability is higher for Indian older adults as compared to other ageing Asian countries. METHODS: Total 1140 aged 60 years and over participated in a baseline study. 560 of them participated in the prospective cohort study conducted in the city of Pune, India. An interview and functional assessment using a questionnaire and Pune-FAAT tool was carried out in 2013-14...
December 2, 2016: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/27936446/design-synthesis-and-evaluation-of-4-aminoquinoline-purine-hybrids-as-potential-antiplasmodial-agents
#14
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
#15
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/27936429/investigation-of-biomechanical-response-of-hoffa-s-fat-pad-and-comparative-characterization
#16
Chiara Giulia Fontanella, Emanuele Luigi Carniel, Alessandro Frigo, Veronica Macchi, Andrea Porzionato, Gloria Sarasin, Marco Rossato, Raffaele De Caro, Arturo N Natali
The infrapatellar adipose body (Hoffa's fat pad, IFP) is situated between the patellar tendon, the femoral condyle and the tibial plateau. The IFP consists of lobules of white adipose tissue delimited by thin connective septa. The actual structural functionality of the IFP is debated and should pertain to a cushioning role in the knee joint, providing to distribute and to damp mechanical stresses during articular activity. The present study is aimed to analyze the correlation between histological configuration and mechanical properties of the IFP, compared to other adipose tissues, partially differentiated by composition and conformation...
December 1, 2016: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/27936417/mesoporous-silica-based-versatile-theranostic-nanoplatform-constructed-by-layer-by-layer-assembly-for-excellent-photodynamic-chemo-therapy
#17
Wei-Hai Chen, Guo-Feng Luo, Wen-Xiu Qiu, Qi Lei, Li-Han Liu, Shi-Bo Wang, Xian-Zheng Zhang
Supramolecular photosensitizers (supraPSs) have emerged as effective photodynamic therapy (PDT) agents. Here, we propose the assembling capacity of supraPSs as a new strategy to construct theranostic nanoplatform with versatile functions aming at high-performance tumor therapy. By coating tirapazamine (TPZ)-loaded mesoporous silica nanoparticles (MSNs) with layer-by-layer (LbL) assembled multilayer, the versatile nanoplatform (TPZ@MCMSN-Gd(3+)) was obtained with the formation of supraPSs via host-guest interaction and the chelation with paramagnetic Gd(3+)...
December 1, 2016: Biomaterials
https://www.readbyqxmd.com/read/27936416/antigen-recognition-triggered-drug-delivery-mediated-by-nanocapsule-functionalized-cytotoxic-t-cells
#18
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
#19
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/27936411/a-network-analysis-of-dsm-5-posttraumatic-stress-disorder-symptoms-and-correlates-in-u-s-military-veterans
#20
Cherie Armour, Eiko I Fried, Marie K Deserno, Jack Tsai, Robert H Pietrzak
OBJECTIVE: Recent developments in psychometrics enable the application of network models to analyze psychological disorders, such as PTSD. Instead of understanding symptoms as indicators of an underlying common cause, this approach suggests symptoms co-occur in syndromes due to causal interactions. The current study has two goals: (1) examine the network structure among the 20 DSM-5 PTSD symptoms, and (2) incorporate clinically relevant variables to the network to investigate whether PTSD symptoms exhibit differential relationships with suicidal ideation, depression, anxiety, physical functioning/quality of life (QoL), mental functioning/QoL, age, and sex...
November 27, 2016: Journal of Anxiety Disorders
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