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https://www.readbyqxmd.com/read/27926874/multivalent-histone-and-dna-engagement-by-a-phd-brd-pwwp-triple-reader-cassette-recruits-zmynd8-to-k14ac-rich-chromatin
#1
Pavel Savitsky, Tobias Krojer, Takao Fujisawa, Jean-Philippe Lambert, Sarah Picaud, Chen-Yi Wang, Erin K Shanle, Krzysztof Krajewski, Hans Friedrichsen, Alexander Kanapin, Colin Goding, Matthieu Schapira, Anastasia Samsonova, Brian D Strahl, Anne-Claude Gingras, Panagis Filippakopoulos
Elucidation of interactions involving DNA and histone post-translational-modifications (PTMs) is essential for providing insights into complex biological functions. Reader assemblies connected by flexible linkages facilitate avidity and increase affinity; however, little is known about the contribution to the recognition process of multiple PTMs because of rigidity in the absence of conformational flexibility. Here, we resolve the crystal structure of the triple reader module (PHD-BRD-PWWP) of ZMYND8, which forms a stable unit capable of simultaneously recognizing multiple histone PTMs while presenting a charged platform for association with DNA...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27923592/developments-in-targeted-therapy-in-melanoma
#2
REVIEW
V C Amann, E Ramelyte, S Thurneysen, R Pitocco, N Bentele-Jaberg, S M Goldinger, R Dummer, J Mangana
Melanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations). The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF- and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma...
November 5, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#3
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27916268/extended-dissipative-state-estimation-for-uncertain-discrete-time-markov-jump-neural-networks-with-mixed-time-delays
#4
Qian Li, Qingxin Zhu, Shouming Zhong, Fuli Zhong
This paper is concerned with the problem of extended dissipativity-based state estimation for uncertain discrete-time Markov jump neural networks with finite piecewise homogeneous Markov chain and mixed time delays. The aim of this paper is to present a Markov switching estimator design method, which ensures that the resulting error system is extended stochastically dissipative. A triple-summable term is introduced in the constructed Lyapunov function and the reciprocally convex approach is utilized to bound the forward difference of the triple-summable term...
December 1, 2016: ISA Transactions
https://www.readbyqxmd.com/read/27913295/dissection-of-functional-lncrnas-in-alzheimer-s-disease-by-construction-and-analysis-of-lncrna-mrna-networks-based-on-competitive-endogenous-rnas
#5
Lian-Kun Wang, Xiao-Feng Chen, Dan-Dan He, You Li, Jin Fu
Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly, and intracellular neurofibrillary tangles (NFTs) are one of the pathological features of AD. Recent studies have suggested long noncoding RNAs (lncRNAs) play important roles in AD. Competing endogenous RNAs (ceRNAs) is a mechanism that has recently been proposed, in which lncRNAs compete for common miRNA-binding sites with mRNAs. However, the roles of lncRNAs and ceRNA in AD NFTs is limited. In this study, we constructed a global triple network based on ceRNA theory, then an AD NFT lncRNA-mRNA network (NFTLMN) was generated...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27891202/new-delay-interval-dependent-stability-criteria-for-switched-hopfield-neural-networks-of-neutral-type-with-successive-time-varying-delay-components
#6
R Manivannan, R Samidurai, Jinde Cao, Ahmed Alsaedi
This paper deals with the problem of delay-interval-dependent stability criteria for switched Hopfield neural networks of neutral type with successive time-varying delay components. A novel Lyapunov-Krasovskii (L-K) functionals with triple integral terms which involves more information on the state vectors of the neural networks and upper bound of the successive time-varying delays is constructed. By using the famous Jensen's inequality, Wirtinger double integral inequality, introducing of some zero equations and using the reciprocal convex combination technique and Finsler's lemma, a novel delay-interval dependent stability criterion is derived in terms of linear matrix inequalities, which can be efficiently solved via standard numerical software...
December 2016: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/27865785/dnmt1-dnmt3a-and-dnmt3b-cooperate-in-photoreceptor-and-outer-plexiform-layer-development-in-the-mammalian-retina
#7
Ratnesh K Singh, Ramya K Mallela, Abigail Hayes, Nicholas R Dunham, Morgan E Hedden, Raymond A Enke, Robert N Fariss, Hal Sternberg, Michael D West, Igor O Nasonkin
Characterizing the role of epigenetic regulation in the mammalian retina is critical for understanding fundamental mechanisms of retinal development and disease. DNA methylation, an epigenetic modifier of genomic DNA, plays an important role in modulating networks of tissue and cell-specific gene expression. However, the impact of DNA methylation during retinal development and homeostasis of retinal neurons remains unclear. Here, we have created a tissue-specific DNA methyltransferase (Dnmt) triple mutant mouse in an effort to characterize the impact of DNA methylation in retinal development and homeostasis...
November 16, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27846853/dgca-a-comprehensive-r-package-for-differential-gene-correlation-analysis
#8
Andrew T McKenzie, Igor Katsyv, Won-Min Song, Minghui Wang, Bin Zhang
BACKGROUND: Dissecting the regulatory relationships between genes is a critical step towards building accurate predictive models of biological systems. A powerful approach towards this end is to systematically study the differences in correlation between gene pairs in more than one distinct condition. RESULTS: In this study we develop an R package, DGCA (for Differential Gene Correlation Analysis), which offers a suite of tools for computing and analyzing differential correlations between gene pairs across multiple conditions...
November 15, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27833464/urology-group-compensation-and-ancillary-service-models-in-an-era-of-value-based-care
#9
Neal D Shore, Dana Jacoby
Changes involving the health care economic landscape have affected physicians' workflow, productivity, compensation structures, and culture. Ongoing Federal legislation regarding regulatory documentation and imminent payment-changing methodologies have encouraged physician consolidation into larger practices, creating affiliations with hospitals, multidisciplinary medical specialties, and integrated delivery networks. As subspecialization and evolution of care models have accelerated, independent medical groups have broadened ancillary service lines by investing in enterprises that compete with hospital-based (academic and nonacademic) entities, as well as non-physician- owned multispecialty enterprises, for both outpatient and inpatient services...
2016: Reviews in Urology
https://www.readbyqxmd.com/read/27817131/reliable-collection-of-real-time-patient-physiologic-data-from-less-reliable-networks-a-monitor-of-monitors-system-moms
#10
Peter F Hu, Shiming Yang, Hsiao-Chi Li, Lynn G Stansbury, Fan Yang, George Hagegeorge, Catriona Miller, Peter Rock, Deborah M Stein, Colin F Mackenzie
Research and practice based on automated electronic patient monitoring and data collection systems is significantly limited by system down time. We asked whether a triple-redundant Monitor of Monitors System (MoMs) to collect and summarize key information from system-wide data sources could achieve high fault tolerance, early diagnosis of system failure, and improve data collection rates. In our Level I trauma center, patient vital signs(VS) monitors were networked to collect real time patient physiologic data streams from 94 bed units in our various resuscitation, operating, and critical care units...
January 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/27798968/prospective-applications-of-ultrahigh-resolution-proteomics-in-clinical-mass-spectrometry
#11
L Renee Ruhaak, Yuri E M van der Burgt, Christa M Cobbaert
Advances in mass spectrometry (MS)-based proteomic strategies have resulted in robust protein biomarker discovery studies often performed on high resolution accurate mass (HRAM) platforms. For successful translation of promising protein biomarkers into useful clinical tests, trans-sector networks and collaboration among stakeholders involved in the biomarker pipeline are urgently needed. Areas covered: In this perspective, literature- and empirical evidence is combined with author's opinions to discuss the progress of ultrahigh resolution MS and provide insight in its potential for validation and development of clinical tests...
November 7, 2016: Expert Review of Proteomics
https://www.readbyqxmd.com/read/27798863/substituted-tetrahydroisoquinolines-as-microtubule-destabilizing-agents-in-triple-negative-human-breast-cancer-cells
#12
Madhavi Gangapuram, Riccardo Jean, Elizabeth Mazzio, Ramesh Badisa, Suresh Eyunni, Carl B Goodman, Kinfe K Redda, Karam F Soliman
Triple-negative breast cancer (TNBC) occurs at greater frequency amongst African-Americans, being characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor 2 (HER2). TNBC is often invasive and typically treated with cytostatic agents such as taxanes in combination with anthracyclines or platinum-based drugs. In this study, we synthesized a number of tetrahydroisoquinoline moieties by N-amination of substituted isoquinolines by O-mesytelene sulfonylhydroxylamine followed by ylide formation and reduction, which yielded the desired, substituted tetrahydroisoquinolines (THIQs) in moderate to good yield...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27795228/neurokinin-1-receptor-antagonist-based-triple-regimens-in-preventing-chemotherapy-induced-nausea-and-vomiting-a-network-meta-analysis
#13
REVIEW
Yaxiong Zhang, Yunpeng Yang, Zhonghan Zhang, Wenfeng Fang, Shiyang Kang, Youli Luo, Jin Sheng, Jianhua Zhan, Shaodong Hong, Yan Huang, Ningning Zhou, Hongyun Zhao, Li Zhang
BACKGROUND: Neurokinin-1 receptor antagonists (NK-1RAs) are widely used for chemotherapy-induced nausea and vomiting (CINV) control in patients with highly emetogenic chemotherapy (HEC) and/or moderately emetogenic chemotherapy (MEC). Whether the efficacy and toxicity of antiemesis are different among various NK-1RA-based triple regimens is unknown. METHODS: Data of complete responses (CRs) in the acute, delayed, and overall phases and treatment-related adverse events (TRAEs) were extracted from electronic databases...
February 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27788485/the-intrinsically-kinase-inactive-ephb6-receptor-predisposes-cancer-cells-to-dr5-induced-apoptosis-by-promoting-mitochondrial-fragmentation
#14
Amr M El Zawily, Behzad M Toosi, Tanya Freywald, Vijaya V Indukuri, Franco J Vizeacoumar, Scot C Leary, Andrew Freywald
Death Receptor 5 (DR5) is a promising target for cancer therapy due to its ability to selectively induce apoptosis in cancer cells. However, the therapeutic usefulness of DR5 agonists is currently limited by the frequent resistance of malignant tumours to its activation. The identification of molecular mechanisms that determine outcomes of DR5 action is therefore crucial for improving the efficiency of DR5-activating reagents in cancer treatment. Here, we provide evidence that an intrinsically kinase-inactive member of the Eph group of receptor tyrosine kinases, EPHB6, induces marked fragmentation of the mitochondrial network in breast cancer cells of triple-negative origin, lacking expression of the estrogen, progesterone and HER2 receptors...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785100/current-advances-in-biomarkers-for-targeted-therapy-in-triple-negative-breast-cancer
#15
REVIEW
Brett Fleisher, Charlotte Clarke, Sihem Ait-Oudhia
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27747192/key-players-in-choline-metabolic-reprograming-in-triple-negative-breast-cancer
#16
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27742306/organ-donation-in-the-united-states-the-tale-of-the-african-american-journey-of-moving-from-the-bottom-to-the-top
#17
C O Callender, N Koizumi, P V Miles, J K Melancon
OBJECTIVE: The purpose was to review the increase of minority organ donation. METHODS: The methodology was based on the efforts of the DC Organ Donor Program and the Dow Take Initiative Program that focused on increasing donors among African Americans (AAs). From 1982 to 1988, AA donor card signings increased from 20/month to 750/month, and Black donations doubled. A review of the data, including face-to-face grassroots presentations combined with national media, was conducted...
September 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27740500/an-improved-result-on-dissipativity-and-passivity-analysis-of-markovian-jump-stochastic-neural-networks-with-two-delay-components
#18
Gnaneswaran Nagamani, Thirunavukkarasu Radhika, Quanxin Zhu
In this paper, we investigate the dissipativity and passivity of Markovian jump stochastic neural networks involving two additive time-varying delays. Using a Lyapunov-Krasovskii functional with triple and quadruple integral terms, we obtain delay-dependent passivity and dissipativity criteria for the system. Using a generalized Finsler lemma (GFL), a set of slack variables with special structure are introduced to reduce design conservatism. The dissipativity and passivity criteria depend on the upper bounds of the discrete time-varying delay and its derivative are given in terms of linear matrix inequalities, which can be efficiently solved through the standard numerical software...
October 10, 2016: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/27738322/antagonizing-mir-218-5p-attenuates-wnt-signaling-and-reduces-metastatic-bone-disease-of-triple-negative-breast-cancer-cells
#19
Hanna Taipaleenmäki, Nicholas H Farina, Andre J van Wijnen, Janet L Stein, Eric Hesse, Gary S Stein, Jane B Lian
Wnt signaling is implicated in bone formation and activated in breast cancer cells promoting primary and metastatic tumor growth. A compelling question is whether osteogenic miRNAs that increase Wnt activity for bone formation are aberrantly expressed in breast tumor cells to support metastatic bone disease. Here we report that miR-218-5p is highly expressed in bone metastases from breast cancer patients, but is not detected in normal mammary epithelial cells. Furthermore, inhibition of miR-218-5p impaired the growth of bone metastatic MDA-MB-231 cells in the bone microenvironment in vivo...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27733827/a-triple-network-connectivity-study-of-large-scale-brain-systems-in-cognitively-normal-apoe4-carriers
#20
Xia Wu, Qing Li, Xinyu Yu, Kewei Chen, Adam S Fleisher, Xiaojuan Guo, Jiacai Zhang, Eric M Reiman, Li Yao, Rui Li
The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach...
2016: Frontiers in Aging Neuroscience
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