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https://www.readbyqxmd.com/read/28431908/implementation-of-a-person-centered-medical-care-model-in-a-skilled-nursing-facility-a-pilot-evaluation
#1
Kathleen Abrahamson, Jaclyn Myers, Arif Nazir
OBJECTIVES: The objective of this study was to evaluate the feasibility and impact of implementing a person-centered medical care model for post-acute care residents within a skilled nursing facility (SNF). DESIGN: A mixed-method (qualitative and quantitative) pilot evaluation. SETTING: An 89-bed SNF located within a large midwestern city. PARTICIPANTS: Forty SNF post-acute patients admitted to the facility during a 6-month period were enrolled in the pilot evaluation...
April 18, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28431046/brg1-interacts-with-sox10-to-establish-the-melanocyte-lineage-and-to-promote-differentiation
#2
Himangi G Marathe, Dawn E Watkins-Chow, Matthias Weider, Alana Hoffmann, Gaurav Mehta, Archit Trivedi, Shweta Aras, Tupa Basuroy, Aanchal Mehrotra, Dorothy C Bennett, Michael Wegner, William J Pavan, Ivana L de la Serna
Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28427211/association-of-brm-promoter-polymorphisms-and-esophageal-adenocarcinoma-outcome
#3
Grzegorz J Korpanty, Lawson Eng, Xin Qiu, Olusola Olusesan Faluyi, Daniel J Renouf, Dangxiao Cheng, Devalben Patel, Zhuo Chen, Brandon C Tse, Jennifer J Knox, Lorin Dodbiba, Jennifer Teichman, Abul Kalam Azad, Rebecca Wong, Gail Darling, David Reisman, Sinead Cuffe, Geoffrey Liu, Wei Xu
PURPOSE: Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients. RESULTS: Of 270 patients, 37% were stage IV. Minor allele frequencies were 47-49%; 15% were double-homozygotes...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#4
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28421159/mammalian-swi-snf-enzymes-and-the-epigenetics-of-tumor-cell-metabolic-reprogramming
#5
REVIEW
Jeffrey A Nickerson, Qiong Wu, Anthony N Imbalzano
Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28420882/the-role-of-the-swi-snf-chromatin-remodeling-complex-in-maintaining-the-stemness-of-glioma-initiating-cells
#6
Hiroaki Hiramatsu, Kazuyoshi Kobayashi, Kyousuke Kobayashi, Takeshi Haraguchi, Yasushi Ino, Tomoki Todo, Hideo Iba
Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420746/the-mitochondrial-dna-mtdna-associated-protein-swib5-influences-mtdna-architecture-and-homologous-recombination
#7
Jonas Blomme, Olivier Van Aken, Jelle Van Leene, Teddy Jégu, Riet Maria De Rycke, Michiel De Bruyne, Jasmien Vercruysse, Jonah Nolf, Twiggy Van Daele, Liesbeth De Milde, Mattias Vermeersch, Catherine Colas des Francs-Small, Geert De Jaeger, Moussa Benhamed, A Harvey Millar, Dirk Inzé, Nathalie Gonzalez
In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared to their animal counterparts and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana...
April 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#8
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastierdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
April 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#9
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#10
Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, Richard Dang, Weisheng Wang, Brian Trieu, Joyce Tong, Ruth M Barrett, Rebecca J Post, Pierre Baldi, Ted Abel, Gary Lynch, Marcelo A Wood
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28411287/impact-of-a-connected-care-model-on-30-day-readmission-rates-from-skilled-nursing-facilities
#11
Luke D Kim, Lei Kou, Bo Hu, Eiran Z Gorodeski, Michael B Rothberg
BACKGROUND: About one-fifth of hospitalized Medicare beneficiaries are discharged to skilled nursing facilities (SNFs) for post-acute care. Readmissions are common but interventions to reduce readmissions are scarce. OBJECTIVE: To assess the impact of a connected care model on 30-day hospital readmission rates among patients discharged to SNFs. DESIGN: Retrospective cohort. SETTING: SNFs that receive referrals from an academic medical center in Cleveland, Ohio...
April 2017: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/28408647/composition-and-function-of-mammalian-swi-snf-chromatin-remodeling-complexes-in-human-disease
#12
John L Pulice, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes play critical roles in maintaining chromatin architecture and gene expression. Genomic sequencing efforts over the past several years have unveiled a major role for these complexes in the development of human cancer as well as neurologic disease, prompting the need to interrogate underlying mechanisms and to develop new methods to comprehensively understand mSWI/SNF complex function. Here we discuss the emerging insights from genetic, biochemical, and functional genomic studies in the field and suggest approaches toward further basic investigations, as well as therapeutic targeting of chromatin remodeling machinery...
April 13, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28408607/crystal-structure-of-the-overlapping-dinucleosome-composed-of-hexasome-and-octasome
#13
Daiki Kato, Akihisa Osakabe, Yasuhiro Arimura, Yuka Mizukami, Naoki Horikoshi, Kazumi Saikusa, Satoko Akashi, Yoshifumi Nishimura, Sam-Yong Park, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Atsushi Matsumoto, Hidetoshi Kono, Rintaro Inoue, Masaaki Sugiyama, Hitoshi Kurumizaka
Nucleosomes are dynamic entities that are repositioned along DNA by chromatin remodeling processes. A nucleosome repositioned by the switch-sucrose nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the intermediate "overlapping dinucleosome." Here, we report the crystal structure of the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14-angstrom resolution. In the overlapping dinucleosome structure, the unusual "hexasome" nucleosome, composed of the histone hexamer lacking one H2A-H2B dimer from the conventional histone octamer, contacts the canonical "octasome" nucleosome, and they intimately associate...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28402505/dicer-and-zrf1-contribute-to-chromatin-decondensation-during-nucleotide-excision-repair
#14
Shalaka Chitale, Holger Richly
Repair of damaged DNA relies on the recruitment of DNA repair factors in a well orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by chromatin remodelers to allow for binding of repair factors and for DNA repair to occur. Recent studies have implicated members of the SWI/SNF and INO80 families as well as PARP1 in nucleotide excision repair (NER). In this study, we report that the endonuclease DICER is implicated in chromatin decondensation during NER. In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner...
April 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28398510/the-swi-snf-atp-dependent-nucleosome-remodeler-promotes-resection-initiation-at-a-dna-double-strand-break-in-yeast
#15
Nathaniel E Wiest, Scott Houghtaling, Joseph C Sanchez, Alan E Tomkinson, Mary Ann Osley
DNA double-strand breaks (DSBs) are repaired by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Pathway choice is determined by the generation of 3΄ single-strand DNA overhangs at the break that are initiated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR. DSB repair occurs in the context of chromatin, and multiple chromatin regulators have been shown to play important roles in the repair process. We have investigated the role of the SWI/SNF ATP-dependent nucleosome-remodeling complex in the repair of a defined DNA DSB...
April 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28396033/improving-transitions-of-care-across-the-spectrum-of-healthcare-delivery-a-multidisciplinary-approach-to-understanding-variability-in-outcomes-across-hospitals-and-skilled-nursing-facilities
#16
Giana H Davidson, Elizabeth Austin, Lucas Thornblade, Louise Simpson, Thuan D Ong, Hanh Pan, David R Flum
INTRODUCTION: Improving coordination during transitions of care from the hospital to Skilled Nursing Facilities (SNF)s is critical for improving healthcare quality. In 2014, we formed (Improving Nursing Facility Outcomes using Real-Time Metrics, INFORM) to improve transitions of care by identifying structural and process factors that lead to poor clinical outcomes and hospital readmission. METHODS: Stakeholders from 10 SNFs and 4 hospitals collaborated to assess the current hospital and system-level challenges to safe transitions of care and identify targets for interventions...
April 5, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28394408/effect-of-clostridium-difficile-prevalence-in-hospitals-and-nursing-homes-on-risk-of-infection
#17
Nina R Joyce, Eleftherios Mylonakis, Vincent Mor
OBJECTIVES: To assess the effect of facility Clostridium difficile infection (CDI) prevalence on risk of healthcare facility (HFC) acquired CDI. DESIGN: Retrospective cohort study. SETTING: Medicare fee-for-service (FFS) claims and skilled nursing facility (SNF) Minimum Data Set 3.0 assessments. PARTICIPANTS: Medicare beneficiaries with 90 days or more of no contact with a HCF before a hospital admission without a CDI diagnosis...
April 10, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28394406/pbrm1-loss-is-a-late-event-during-the-development-of-cholangiocarcinoma
#18
Claudio Luchini, Scott A Robertson, Seung Mo Hong, Matthäus Felsenstein, Robert A Anders, Antonio Pea, Alessia Nottegar, Nicola Veronese, Jin He, Matthew J Weiss, Paola Capelli, Aldo Scarpa, Pedram Argani, Payal Kapur, Laura D Wood
Somatic mutations in genes encoding chromatin remodelers have been recently reported in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodelers in cholangiocarcinoma is the PBRM1 gene located on chromosome 3p21, which encodes a subunit of the SWI/SNF complex. In order to determine the timing of PBRM1 mutations in biliary carcinogenesis, we used immunohistochemistry to assess PBRM1 protein expression in a series of precursor lesions and invasive biliary carcinomas...
April 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28394097/tolerance-or-avoidance-drought-frequency-determines-the-response-of-an-n2-fixing-tree
#19
Jeffrey M Minucci, Chelcy Ford Miniat, Robert O Teskey, Nina Wurzburger
Climate change is increasing drought frequency, which may affect symbiotic N2 fixation (SNF), a process that facilitates ecosystem recovery from disturbance. Here, we assessed the effect of drought frequency on the ecophysiology and SNF rate of a common N2 -fixing tree in eastern US forests. We grew Robinia pseudoacacia seedlings under the same mean soil moisture, but with different drought frequency caused by wet-dry cycles of varying periodicity. We found no effect of drought frequency on final biomass or mean SNF rate...
April 10, 2017: New Phytologist
https://www.readbyqxmd.com/read/28391084/mammalian-swi-snf-complexes-in-cancer-emerging-therapeutic-opportunities
#20
REVIEW
Roodolph St Pierre, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations...
April 5, 2017: Current Opinion in Genetics & Development
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