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https://www.readbyqxmd.com/read/28433225/adjuvant-chemotherapy-is-associated-with-improved-survival-in-locally-invasive-node-negative-non-small-cell-lung-cancer
#1
Usman Ahmad, Traves D Crabtree, Aalok P Patel, Daniel Morgensztern, Cliff G Robinson, A Sasha Krupnick, Daniel Kreisel, David R Jones, G Alexander Patterson, Bryan F Meyers, Varun Puri
BACKGROUND: The objectives of this study are to explore factors that are associated with use of adjuvant chemotherapy and to evaluate its impact on overall survival in node-negative patients who undergo lung and chest wall resection for non-small cell lung cancer (NSCLC). METHODS: Patients who underwent concomitant lung and chest wall resection for NSCLC were abstracted from the National Cancer Database. Clinical, pathologic, treatment, and follow-up data were obtained...
April 19, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28425697/conserved-helix-flanking-prolines-modulate-idp-target-affinity-by-altering-the-lifetime-of-the-bound-complex
#2
Michael David Crabtree, Wade Borcherds, Anusha Poosapati, Sarah L Shammas, Gary W Daughdrill, Jane Clarke
Appropriate integration of cellular signals requires a delicate balance of ligand-target binding affinities. Increasing residual structure in intrinsically disordered proteins (IDPs), which are overrepresented in these cellular processes, has been shown previously to enhance binding affinities and alter cellular function. Conserved proline residues are commonly found flanking regions of IDPs that become helical upon interacting with a partner protein. Here, we mutate these helix-flanking prolines in p53 and MLL, and find opposite effects on binding affinity upon increasing free IDP helicity...
April 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28402856/chd8-mutation-leads-to-autistic-like-behaviors-and-impaired-striatal-circuits
#3
Randall J Platt, Yang Zhou, Ian M Slaymaker, Ashwin S Shetty, Niels R Weisbach, Jin-Ah Kim, Jitendra Sharma, Mitul Desai, Sabina Sood, Hannah R Kempton, Gerald R Crabtree, Guoping Feng, Feng Zhang
Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically defined models can provide an entry point to studying the molecular underpinnings of this disorder. We generated germline mutant mice with loss-of-function mutations in Chd8, a de novo mutation strongly associated with ASD, and demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and craniofacial abnormalities similar to patient phenotypes. Chd8(+/-) mice display a broad, brain-region-specific dysregulation of major regulatory and cellular processes, most notably histone and chromatin modification, mRNA and protein processing, Wnt signaling, and cell-cycle regulation...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28398251/proteolysis-in-helicobacter-pylori-induced-gastric-cancer
#4
REVIEW
Gernot Posselt, Jean E Crabtree, Silja Wessler
Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark of H. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules...
April 11, 2017: Toxins
https://www.readbyqxmd.com/read/28376928/-these-people-you-just-guide-them-until-they-become-these-people-learning-to-become-a-frequent-indoor-tanner
#5
Jerod L Stapleton, Benjamin F Crabtree
BACKGROUND: Many young women experiment with using indoor tanning beds with some becoming regular users. There is a dearth of research focused on factors related to the development of regular tanning. This study was designed to gain an in-depth understanding of the experiences of a regular indoor tanning bed user for the purpose of discovering working hypotheses related to the development of this behavior. The article thesis is that initial interactions with tanning salon employees transmit insider knowledge that serves to encourage the regular use of indoor tanning beyond experimentation...
April 4, 2017: BMC Psychology
https://www.readbyqxmd.com/read/28371603/triosephosphates-as-intermediates-of-the-crabtree-effect
#6
S S Sokolov, O V Markova, K D Nikolaeva, I A Fedorov, F F Severin
An increase in glucose concentration in the medium rapidly decreases respiration rate in many cell types, including tumor cells. The molecular mechanism of this phenomenon, the Crabtree effect, is still unclear. It was shown earlier that adding the intermediate product of glycolysis fructose-1,6-bisphosphate to isolated mitochondria suppresses their respiration. To study possible roles of glycolytic intermediates in the Crabtree effect, we used a model organism, the yeast Saccharomyces cerevisiae. To have the option to rapidly increase intracellular concentrations of certain glycolytic intermediates, we used mutant cells with glycolysis blocked at different stages...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28349709/meeting-report
#7
Barry H Ginsberg, David C Klonoff, Vincent P Crabtree
On July 6 and 7, 2016 the Fourth Artificial Pancreas Workshop: Testing and Adoption of Current and Emerging Technologies was held on the National Institutes of Health (NIH) Campus at the Lister Hill Auditorium. The meeting was sponsored by a group of governmental organizations and NGOs, listed in Appendix A. This was a very timely meeting as the artificial pancreas appears to be growing from academic studies to commercial projects. The first artificial pancreas may be marketed within 12 months and a few may be approved within 24 months...
March 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28323974/phenotypic-spectrum-in-osteogenesis-imperfecta-due-to-mutations-in-tmem38b-unravelling-a-complex-cellular-defect
#8
Emma A Webb, Meena Balasubramanian, Nadja Fratzl-Zelman, Wayne A Cabral, Hannah Titheradge, Atif Alsaedi, Vrinda Saraff, Julie Vogt, Trevor Cole, Susan Stewart, Nicola J Crabtree, Brandi M Sargent, Sonja Gamsjaeger, Eleftherios P Paschalis, Paul Roschger, Klaus Klaushofer, Nick J Shaw, Joan C Marini, Wolfgang Högler
Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy...
March 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28289968/synthesis-and-in-vitro-and-in-vivo-evaluation-of-3-h-lrrk2-in-1-as-a-novel-radioligand-for-lrrk2
#9
Noeen Malik, Andrew N Gifford, Johan Sandell, Daniel Tuchman, Yu-Shin Ding
PURPOSE: LRRK2 (leucine-rich repeat kinase 2) has recently been proven to be a promising drug target for Parkinson's disease (PD) due to an apparent enhanced activity caused by mutations associated with familial PD. To date, there have been no reports in which a LRRK2 inhibitor has been radiolabeled and used for in in vitro or in vivo studies of LRRK2. In the present study, we radiolabeled the LRRK2 ligand, LRRK-IN-1, for the purposes of performing in vitro (IC50, K d , B max, autoradiography) and in vivo (biodistribution, and blocking experiments) evaluations in rodents and human striatum tissues...
March 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28283561/alteration-of-neuronal-excitability-and-short-term-synaptic-plasticity-in-the-prefrontal-cortex-of-a-mouse-model-of-mental-illness
#10
Gregg W Crabtree, Ziyi Sun, Mirna Kvajo, Jantine A C Broek, Karine Fénelon, Heather McKellar, Lan Xiao, Bin Xu, Sabine Bahn, James M O'Donnell, Joseph A Gogos
Using a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28282411/coevolution-with-bacteria-drives-the-evolution-of-aerobic-fermentation-in-lachancea-kluyveri
#11
Nerve Zhou, Krishna B S Swamy, Jun-Yi Leu, Michael J McDonald, Silvia Galafassi, Concetta Compagno, Jure Piškur
The Crabtree positive yeasts, such as Saccharomyces cerevisiae, prefer fermentation to respiration, even under fully aerobic conditions. The selective pressures that drove the evolution of this trait remain controversial because of the low ATP yield of fermentation compared to respiration. Here we propagate experimental populations of the weak-Crabtree yeast Lachancea kluyveri, in competitive co-culture with bacteria. We find that L. kluyveri adapts by producing quantities of ethanol lethal to bacteria and evolves several of the defining characteristics of Crabtree positive yeasts...
2017: PloS One
https://www.readbyqxmd.com/read/28274565/the-american-association-for-thoracic-surgery-consensus-guidelines-for-the-management-of-empyema
#12
K Robert Shen, Alejandro Bribriesco, Traves Crabtree, Chad Denlinger, Joshua Eby, Patrick Eiken, David R Jones, Shaf Keshavjee, Fabien Maldonado, Subroto Paul, Benjamin Kozower
No abstract text is available yet for this article.
February 4, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28272869/a-pyridine-alkoxide-chelate-ligand-that-promotes-both-unusually-high-oxidation-states-and-water-oxidation-catalysis
#13
Thoe K Michaelos, Dimitar Y Shopov, Shashi Bhushan Sinha, Liam S Sharninghausen, Katherine J Fisher, Hannah M C Lant, Robert H Crabtree, Gary W Brudvig
Water-oxidation catalysis is a critical bottleneck in the direct generation of solar fuels by artificial photosynthesis. Catalytic oxidation of difficult substrates such as water requires harsh conditions, so the ligand must be designed both to stabilize high oxidation states of the metal center and to strenuously resist ligand degradation. Typical ligand choices either lack sufficient electron donor power or fail to stand up to the oxidizing conditions. Our research on Ir-based water-oxidation catalysts (WOCs) has led us to identify a ligand, 2-(2'-pyridyl)-2-propanoate or "pyalk", that fulfills these requirements...
March 8, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28270511/quantifying-intracellular-rates-of-glycolytic-and-oxidative-atp-production-and-consumption-using-extracellular-flux-measurements
#14
Shona A Mookerjee, Akos A Gerencser, David G Nicholls, Martin D Brand
Partitioning of ATP generation between glycolysis and oxidative phosphorylation is central to cellular bioenergetics but cumbersome to measure. We describe here how rates of ATP generation by each pathway can be calculated from simultaneous measurements of extracellular acidification and oxygen consumption. We update theoretical maximum ATP yields by mitochondria and cells catabolizing differ- ent substrates. Mitochondrial P/O ratios are 2.73 for oxidation of pyruvate plus malate and 1.64 for oxidation of succinate...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28253434/a-general-non-radioactive-atpase-assay-for-chromatin-remodeling-complexes
#15
Benjamin Z Stanton, Courtney Hodges, Gerald R Crabtree, Keji Zhao
Chromatin remodeling complexes couple the energy released from ATP hydrolysis to facilitate transcription, recombination, and repair mechanisms essential for a wide variety of biologic responses. While recombinant expression of the regulatory subunits of these enzymes is possible, measuring catalytic (ATPase) activity of the intact complexes recovered from normal or mutant cells is critical for understanding their mechanisms. SWI/SNF-like remodeling complexes can be megadaltons in size and include many regulatory subunits, making reconstitution of purified subunits challenging for recapitulating in vivo function...
March 2, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/28250416/top2-synergizes-with-baf-chromatin-remodeling-for-both-resolution-and-formation-of-facultative-heterochromatin
#16
Erik L Miller, Diana C Hargreaves, Cigall Kadoch, Chiung-Ying Chang, Joseph P Calarco, Courtney Hodges, Jason D Buenrostro, Kairong Cui, William J Greenleaf, Keji Zhao, Gerald R Crabtree
The resolution and formation of facultative heterochromatin are essential for development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood owing to the difficulty of studying heterochromatin dynamics and structure in vivo. We devised an in vivo approach to investigate these mechanisms and found that topoisomerase II (TOP2), but not TOP1, synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin independent of transcription...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28240328/hypervalency-secondary-bonding-and-hydrogen-bonding-siblings-under-the-skin
#17
Robert H Crabtree
In hypervalent bonding (HVB), secondary bonding (SB) and hydrogen bonding (HB) a nucleophilic and an electrophilic partner form a new bond that is based on a similar bonding pattern across the whole series of interactions. The electrostatic contribution is reflected in the 'σ hole' model in which a positive patch on E attracts the nucleophilic component. The nucleophile, Y, possesses a corresponding negative patch, resulting in a linear structure YE-X having one strong E-X bond and one weaker, longer YE interaction; this is considered as a SB interaction between Y and E...
March 21, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28218929/enhancing-resilience-in-active-duty-military-personnel
#18
Sonya Crabtree-Nelson, Lcdr Peter DeYoung
A systematic, evidence-based training program to support active duty military personnel through building unit-level resiliency in preparation for anticipated individual times of crisis is needed. Mental health nurses and social workers in the military possess critical training and expertise in identifying and supporting individual and community resilience factors. Their knowledge of the protective aspects of resilience can and should be used to educate all active duty military personnel, ensure military leaders are knowledgeable in how best to support their units, and provide research on the effectiveness of pre-combat resilience training...
February 1, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28199350/25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-exert-distinct-effects-on-human-skeletal-muscle-function-and-gene-expression
#19
Zaki K Hassan-Smith, Carl Jenkinson, David J Smith, Ivan Hernandez, Stuart A Morgan, Nicola J Crabtree, Neil J Gittoes, Brian G Keevil, Paul M Stewart, Martin Hewison
Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers...
2017: PloS One
https://www.readbyqxmd.com/read/28189053/hypoxia-and-iron-requirements-are-the-main-drivers-in-transcriptional-adaptation-of-kluyveromyces-lactis-during-wine-aerobic-fermentation
#20
Jordi Tronchoni, Alda J Rodrigues, Jose Antonio Curiel, Pilar Morales, Ramon Gonzalez
The respiratory metabolism of yeast species alternative to Saccharomyces cerevisiae has been explored in recent years as a tool to reduce ethanol content in grape wine. The efficacy of this strategy has been previously proven for mixed cultures of non-Saccharomyces and S. cerevisiae strains. In this work, we perform a transcriptomic analysis of the Crabtree-negative yeast Kluyveromyces lactis under tightly controlled growth conditions in order to better understand physiology of non-Saccharomyces yeasts during the fermentation of grape must under aerated conditions...
January 27, 2017: International Journal of Food Microbiology
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