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https://www.readbyqxmd.com/read/28641126/dna-requirements-for-interaction-of-the-c-terminal-region-of-ku80-with-the-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs
#1
Sarvan Kumar Radhakrishnan, Susan P Lees-Miller
Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks (DSBs) in human cells. Critical to NHEJ is the DNA-dependent interaction of the Ku70/80 heterodimer with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the DNA-PK holoenzyme. However, precisely how Ku recruits DNA-PKcs to DSBs ends to enhance its kinase activity has remained enigmatic, with contradictory findings reported in the literature. Here we address the role of the Ku80 C-terminal region (CTR) in the DNA-dependent interaction of Ku70/80 with DNA-PKcs using purified components and defined DNA structures...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641116/mechanisms-for-selective-single-cell-reactivation-during-offline-sharp-wave-ripples-and-their-distortion-by-fast-ripples
#2
Manuel Valero, Robert G Averkin, Ivan Fernandez-Lamo, Juan Aguilar, Diego Lopez-Pigozzi, Jorge R Brotons-Mas, Elena Cid, Gabor Tamas, Liset Menendez de la Prida
Memory traces are reactivated selectively during sharp-wave ripples. The mechanisms of selective reactivation, and how degraded reactivation affects memory, are poorly understood. We evaluated hippocampal single-cell activity during physiological and pathological sharp-wave ripples using juxtacellular and intracellular recordings in normal and epileptic rats with different memory abilities. CA1 pyramidal cells participate selectively during physiological events but fired together during epileptic fast ripples...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#3
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28641093/hematological-parameters-and-red-blood-cell-morphological-abnormality-of-glucose-6-phosphate-dehydrogenase-deficiency-co-inherited-with-thalassemia
#4
Jutharat Pengon, Saovaros Svasti, Sumalee Kamchonwongpaisan, Phantip Vattanaviboon
OBJECTIVE/BACKGROUND: Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and thalassemia are genetically independent hemolytic disorders. Co-inheritance of both disorders may affect red blood cell pathology to a greater extent than normally seen in either disorder alone. This study determines the prevalence and evaluates hematological changes of G-6-PD deficiency and thalassemia co-inheritance. METHODS: G-6-PD deficiency was screened from 200 male thalassemia blood samples using a fluorescent spot test...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28640993/locking-in-optimal-nanoscale-structure-induced-by-naphthalenediimide-based-polymeric-additive-enables-efficient-and-stable-inverted-polymer-solar-cells
#5
Kwang Hyun Park, Yujin An, Seungon Jung, Hyesung Park, Changduk Yang
Operational stability and high performance are the most critical issues that must be addressed in order to propel and advance the current polymer solar cell (PSC) technology to the next level such as manufacturing and mass production. Herein, we report a high power conversion efficiency (PCE) of 11.2% together with an excellent device stability in PTB7-Th:PC71BM-based PSCs in the inverted structure by introducing the n-type P(NDI2OD-T2) macromolecular additive (>75% PCE retention at high temperature up to 120 °C, >97% PCE retention after 6 months in inert conditions, >93% PCE retention after 2 months in air with encapsulation, and >80% PCE retention after 140 h in air without encapsulation)...
June 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#6
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28640939/global-transcriptome-and-co-expression-network-analyses-reveal-cultivar-specific-molecular-signatures-associated-with-seed-development-and-seed-size-weight-determination-in-chickpea
#7
Rohini Garg, Vikash K Singh, Mohan Singh Rajkumar, Vinay Kumar, Mukesh Jain
Seed development is an intricate process regulated via a complex transcriptional regulatory network. To understand the molecular mechanisms governing seed development and seed size/weight in chickpea, we performed a comprehensive analysis of transcriptome dynamics during seed development in two cultivars with contrasting seed size/weight (small seeded, Himchana 1 and large-seeded, JGK 3). Our analysis identified stage-specific expression for a significant proportion (>13%) of the genes. About one-fourth of total genes exhibited significant differential expression in JGK 3 as compared to Himchana 1...
June 22, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28640835/bilateral-blockade-of-mek-and-pi3k-mediated-pathways-downstream-of-mutant-kras-as-a-treatment-approach-for-peritoneal-mucinous-malignancies
#8
Murali R Kuracha, Peter Thomas, Brian W Loggie, Venkatesh Govindarajan
Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#9
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28640612/crispr-cas9-based-genome-editing-for-disease-modeling-and-therapy-challenges-and-opportunities-for-nonviral-delivery
#10
Hong-Xia Wang, Mingqiang Li, Ciaran M Lee, Syandan Chakraborty, Hae-Won Kim, Gang Bao, Kam W Leong
Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors...
June 22, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28637324/the-effects-of-phytosterols-on-the-sexual-behavior-and-reproductive-function-in-the-japanese-quail-coturnix-coturnix-japonica
#11
Mohammad Ibrahim Qasimi, Kentaro Nagaoka, Gen Watanabe
Phytosterols (PS) are plant origin sterols naturally found in many foods and added as food additives. Since 1950, PS have attracted considerable attention due to their ability to lower serum cholesterol and inhibit cardiovascular disease (CVD). However, recent studies have found that PS act as endocrine-disrupting chemicals in laboratory animals. Therefore, this study was aimed at finding the mechanism(s) for PS effects on the sexual behaviors and reproductive functions in male Japanese quails (Coturnix coturnix japonica)...
June 16, 2017: Poultry Science
https://www.readbyqxmd.com/read/28637323/evolution-of-transcription-activator-like-effectors-in-xanthomonas-oryzae
#12
Annett Erkes, Maik Reschke, Jens Boch, Jan Grau
Transcription activator-like effectors (TALEs) are secreted by plant-pathogenic Xanthomonas bacteria into plant cells where they act as transcriptional activators and, hence, are major drivers in reprogramming the plant for the benefit of the pathogen. TALEs possess a highly repetitive DNA-binding domain of typically 34 amino acid tandem repeats, where amino acid 12 and 13, termed repeat variable di-residue (RVD), determine target specificity. Different Xanthomonas strains possess different repertoires of TALEs...
June 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28637250/use-of-spytag-spycatcher-to-construct-bispecific-antibodies-that-target-two-epitopes-of-a-single-antigen
#13
Kyohei Yumura, Hiroki Akiba, Satoru Nagatoishi, Osamu Kusano-Arai, Hiroko Iwanari, Takao Hamakubo, Kouhei Tsumoto
Bispecific antibody targeting of two different antigens is promising, but when fragment-based antibodies are used, homogeneous production is difficult. To overcome this difficulty, we developed a method using the SpyTag/SpyCatcher system in which a covalent bond is formed between the two polypeptides. Using this method, we constructed a bispecific antibody that simultaneously interacted with two different epitopes of ROBO1, a membrane protein associated with cancer progression. A bispecific tetravalent antibody with an additional functional moiety was also constructed by using a dimeric biotin-binding protein...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28637183/nuclitrack-an-integrated-nuclei-tracking-application
#14
Sam Cooper, Alexis R Barr, Robert Glen, Chris Bakal
Summary: Live imaging studies give unparalleled insight into dynamic single cell behaviours and fate decisions. However, the challenge of reliably tracking single cells over long periods of time limits both the throughput and ease with which such studies can be performed. Here, we present NucliTrack, a cross platform solution for automatically segmenting, tracking and extracting features from fluorescently-labelled nuclei. NucliTrack performs similarly to other state-of-the-art cell tracking algorithms, but NucliTrack's interactive, graphical interface makes it significantly more user friendly...
June 20, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#15
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#16
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636983/the-influence-of-marital-status-on-survival-in-patients-with-oral-tongue-squamous-cell-carcinoma
#17
Wei Sun, Zeting Qiu, Wulin Tan, Zhongqi Liu, Zhongxing Wang, Wenqi Huang, Minghui Cao
Marital status was found to be an independent prognostic factor for survival in several cancers. However related researches of oral tongue squamous cell carcinoma (OTSCC) are still rare. We explored the Surveillance, Epidemiology, and End Results (SEER) program and finally identified 14,194 patients with OTSCC. Kaplan-Meier analysis and multivariate Cox regression models were used to distinguish risk factors for overall survival (OS) and tumor cause-specific survival (TCSS). Widowed patients had the highest percentage of female, highest average ages and more prevalence with localized SEER Stage significantly, while patients in the single group were younger than other groups...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636917/kinesin-processivity-is-determined-by-a-kinetic-race-from-a-vulnerable-one-head-bound-state
#18
Keith J Mickolajczyk, William O Hancock
Kinesin processivity, defined as the average number of steps that occur per interaction with a microtubule, is an important biophysical determinant of the motor's intracellular capabilities. Despite its fundamental importance to the diversity of tasks that kinesins carry out in cells, no existing quantitative model fully explains how structural differences between kinesins alter kinetic rates in the ATPase cycle to produce functional changes in processivity. Here we use high-resolution single-molecule microscopy to directly observe the stepping behavior of kinesin-1 and -2 family motors with different length neck-linker domains...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636806/ph-dependent-general-base-catalyzed-activation-rather-than-isocyanate-liberation-may-explain-the-superior-anticancer-efficacy-of-laromustine-compared-to-related-1-2-bis-methylsulfonyl-1-2-chloroethyl-hydrazine-prodrugs
#19
P G Penketh, R A Finch, R Sauro, R P Baumann, E S Ratner, K Shyam
Laromustine (also known as cloretazine, onrigin, VNP40101M, 101M) is a prodrug of 90CE, a short-lived chloroethylating agent with anticancer activity. The short half-life of 90CE necessitates the use of latentiated prodrug forms for in vivo treatments. Alkylaminocarbonyl based prodrugs such as laromustine exhibit significantly superior in vivo activity in several murine tumor models compared to analogs utilizing acyl, and alkoxycarbonyl latentiating groups. The alkylaminocarbonyl prodrugs possess two exclusive characteristics: (i) they are primarily unmasked by spontaneous base catalyzed elimination; and (ii) they liberate a reactive carbamoylating species...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#20
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
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