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https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#1
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28906284/effect-of-transfusion-on-mortality-and-other-adverse-events-among-critically-ill-septic-patients-an-observational-study-using-a-marginal-structural-cox-model
#2
Claire Dupuis, Maité Garrouste-Orgeas, Sébastien Bailly, Christophe Adrie, Dany Goldgran-Toledano, Elie Azoulay, Stéphane Ruckly, Guillaume Marcotte, Bertrand Souweine, Michael Darmon, Yves Cohen, Carole Schwebel, Guillaume Lacave, Lila Bouadma, Jean-Francois Timsit
OBJECTIVES: RBC transfusion is often required in patients with sepsis. However, adverse events have been associated with RBC transfusion, raising safety concerns. A randomized controlled trial validated the 7 g/dL threshold, but previously transfused patients were excluded. Cohort studies led to conflicting results and did not handle time-dependent covariates and history of treatment. Additional data are thus warranted to guide patient's management. DESIGN: To estimate the effect of one or more RBC within 1 day on three major outcomes (mortality, ICU-acquired infections, and severe hypoxemia) at day 30, we used marginal structural models...
September 12, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28888693/n-terminus-determines-activity-and-specificity-of-styrene-monooxygenase-reductases
#3
Thomas Heine, Anika Scholtissek, Adrie H Westphal, Willem J H van Berkel, Dirk Tischler
Styrene monooxygenases (SMOs) are two-enzyme systems that catalyze the enantioselective epoxidation of styrene to (S)-styrene oxide. The FADH2 co-substrate of the epoxidase component (StyA) is supplied by an NADH-dependent flavin reductase (StyB). The genome of Rhodococcus opacus 1CP encodes two SMO systems. One system, which we define as E1-type, displays homology to the SMO from Pseudomonas taiwanensis VLB120. The other system, originally reported as a fused system (RoStyA2B), is defined as E2-type. Here we found that E1-type RoStyB is inhibited by FMN, while RoStyA2B is known to be active with FMN...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28884568/computational-study-of-low-interlayer-friction-in-tin-1cn-n-1-2-and-3-mxene
#4
Difan Zhang, Michael Ashton, Alireza Ostadhossein, Adri C T van Duin, Richard G Hennig, Susan B Sinnott
The friction of adjacent Tin+1Cn (n=1, 2 and 3) MXene layers is investigated using density functional theory (DFT) calculations and classical molecular dynamics (MD) simulations with ReaxFF potentials. The calculations reveal the sliding pathways in all three MXene systems with low energy barriers. The friction coefficients for interlayer sliding are evaluated using static calculations. Both DFT and ReaxFF methods predict friction coefficients between 0.24 and 0.27 for normal loads less than 1.2 GPa. The effect of titanium (Ti) vacancies in sublayers and terminal oxygen (O) vacancies at surfaces on the interlayer friction is further investigated using the ReaxFF potential...
September 8, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28810729/thermal-stability-of-organic-monolayers-grafted-to-si-111-insights-from-reaxff-reactive-molecular-dynamics-simulations
#5
Federico A Soria, Weiwei Zhang, Adri C T van Duin, Eduardo M Patrito
We used the ReaxFF reactive molecular dynamics simulations to investigate the chemical mechanisms and kinetics of thermal decomposition processes of silicon surfaces grafted with different organic molecules via Si-C bonds at atomistic level. In this work, we considered the Si(111) surface grafted with n-alkyl (ethyl, propyl, pentyl, and decyl) layers in 50% coverage and, Si-CH3, Si-CCCH3 and Si-CHCHCH3 layers in full coverage. Si radicals primarily formed by the homolytic cleavage of Si-C bonds play a key role in the dehydrogenation processes that lead to the decomposition of the monolayers...
September 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28794182/membrane-filtration-is-suitable-to-reliably-eliminate-mycobacterium-tuberculosis-from-saliva-for-therapeutic-drug-monitoring
#6
Simone H J van den Elsen, Tridia van der Laan, Onno W Akkerman, Adri G M van der Zanden, Jan-Willem C Alffenaar, Dick van Soolingen
Tuberculosis (TB) remains an infectious disease of a worldwide concern.….
August 9, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28791878/role-of-ergothioneine-in-microbial-physiology-and-pathogenesis
#7
Bridgette M Cumming, Krishna C Chinta, Vineel P Reddy, Adrie J C Steyn
SIGNIFICANCE: L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria, and some fungi. In contrast to other low-molecular-weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological pH, which makes it resistant to autoxidation. Ergothioneine regulates microbial physiology and enables the survival of microbes under stressful conditions encountered in their natural environments. In particular, ergothioneine enables pathogenic microbes, such as Mycobacterium tuberculosis (Mtb), to withstand hostile environments within the host to establish infection...
September 8, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28760899/susceptibility-of-mycobacterium-tuberculosis-cytochrome-bd-oxidase-mutants-to-compounds-targeting-the-terminal-respiratory-oxidase-cytochrome-c
#8
Atica Moosa, Dirk A Lamprecht, Kriti Arora, Clifton E Barry, Helena I M Boshoff, Thomas R Ioerger, Adrie J C Steyn, Valerie Mizrahi, Digby F Warner
We deleted subunits I (cydA) and II (cydB) of the Mycobacterium tuberculosis cytochrome bd menaquinol oxidase. The resulting ΔcydA and ΔcydAB mutants were hypersusceptible to compounds targeting the mycobacterial bc1 menaquinol-cytochrome c oxidoreductase, and exhibited bioenergetic profiles indistinguishable from strains deficient in the ABC-type transporter, CydDC, predicted to be essential for cytochrome bd assembly. These results confirm CydAB and CydDC as potential targets for drugs aimed at inhibiting a terminal respiratory oxidase implicated in pathogenesis...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28753915/colorful-packages-encapsulation-of-fluorescent-proteins-in-complex-coacervate-core-micelles
#9
Antsje Nolles, Adrie H Westphal, J Mieke Kleijn, Willem J H van Berkel, Jan Willem Borst
Encapsulation of proteins can be beneficial for food and biomedical applications. To study their biophysical properties in complex coacervate core micelles (C3Ms), we previously encapsulated enhanced green fluorescent protein (EGFP) and its monomeric variant, mEGFP, with the cationic-neutral diblock copolymer poly(2-methyl-vinyl-pyridinium)n-b-poly(ethylene-oxide)m (P2MVPn-b-PEOm) as enveloping material. C3Ms with high packaging densities of fluorescent proteins (FPs) were obtained, resulting in a restricted orientational freedom of the protein molecules, influencing their structural and spectral properties...
July 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28748346/trends-in-incidence-and-tumour-grade-in-screen-detected-ductal-carcinoma-in-situ-and-invasive-breast-cancer
#10
Jacky D Luiten, Adri C Voogd, Ernest J T Luiten, Lucien E M Duijm
PURPOSE: In a biennial screening mammography programme, we analysed the trends in incidence of screen-detected DCIS and invasive breast cancers in the era of screen-film mammography (SFM) screening, the period of the transition to full-field digital mammography (FFDM) screening and the period of FFDM screening. We also investigated a possible association between the incidence and grading of screen-detected DCIS and invasive breast cancer. METHODS: In the southern part of the Netherlands, FFDM screening gradually replaced SFM screening between May 2009 and April 2010...
July 26, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28708888/correction-mycobacterium-tuberculosis-arrests-host-cycle-at-the-g1-s-transition-to-establish-long-term-infection
#11
Bridgette M Cumming, Md Aejazur Rahman, Dirk A Lamprecht, Kyle H Rohde, Vikram Saini, John H Adamson, David G Russell, Adrie J C Steyn
[This corrects the article DOI: 10.1371/journal.ppat.1006389.].
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28707104/microbial-hydrocarbon-formation-from-biomass
#12
Adrie J J Straathof, Maria C Cuellar
Fossil carbon sources mainly contain hydrocarbons, and these are used on a huge scale as fuel and chemicals. Producing hydrocarbons from biomass instead is receiving increased attention. Achievable yields are modest because oxygen atoms need to be removed from biomass, keeping only the lighter carbon and hydrogen atoms. Microorganisms can perform the required conversions, potentially with high selectivity, using metabolic pathways that often end with decarboxylation. Metabolic and protein engineering are used successfully to achieve hydrocarbon production levels that are relevant in a biorefinery context...
July 14, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28670303/3-hydroxybenzoate-6-hydroxylase-from-rhodococcus-jostii-rha1-contains-a-phosphatidylinositol-cofactor
#13
Stefania Montersino, Evelien Te Poele, Roberto Orru, Adrie H Westphal, Arjan Barendregt, Albert J R Heck, Robert van der Geize, Lubbert Dijkhuizen, Andrea Mattevi, Willem J H van Berkel
3-Hydroxybenzoate 6-hydroxylase (3HB6H, EC 1.13.14.26) is a FAD-dependent monooxygenase involved in the catabolism of aromatic compounds in soil microorganisms. 3HB6H is unique among flavoprotein hydroxylases in that it harbors a phospholipid ligand. The purified protein obtained from expressing the gene encoding 3HB6H from Rhodococcus jostii RHA1 in the host Escherichia coli contains a mixture of phosphatidylglycerol and phosphatidylethanolamine, which are the major constituents of E. coli's cytoplasmic membrane...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28656490/different-outcome-in-node-positive-breast-cancer-patients-found-by-axillary-ultrasound-or-sentinel-node-procedure
#14
Nicole C Verheuvel, Adri C Voogd, Vivianne C G Tjan-Heijnen, S Siesling, Rudi M H Roumen
BACKGROUND: The Z0011 trial initiated a paradigm shift in the axillary treatment of breast cancer patients with a positive sentinel lymph node biopsy (SLNB), disregarding patients with a positive ultrasound-guided lymph node biopsy (UGLNB). We examined whether relevant differences exist between these patients to determine if the conclusions of the ACOSOG Z0011 trial are applicable to UGLNB-positive patients. METHODS: Patients diagnosed with invasive breast cancer in the Netherlands between January 2008 and December 2014 were selected from the Netherlands Cancer Registry...
June 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28655326/treatment-of-severe-hospital-acquired-and-ventilator-associated-pneumonia-a-systematic-review-of-inclusion-and-judgment-criteria-used-in-randomized-controlled-trials
#15
Emmanuel Weiss, Wafa Essaied, Christophe Adrie, Jean-Ralph Zahar, Jean-François Timsit
BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are often selected for randomized clinical trials (RCTs) aiming at new drug approval. Guidelines for the design of such RCTs have been repeatedly updated by regulatory agencies. We hypothesized that large variability in the enrolled populations, the endpoints assessed and the HAP/VAP definition criteria may impact the results of these studies, and addressed this through a systematic review of HAP/VAP RCTs. METHODS: A search (Pubmed-Embase-ICAAC-ECCMID) of all RCTs published between 1994 and 2016 comparing antimicrobial treatment for HAP/VAP in the intensive care unit was conducted...
June 27, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28655276/modified-random-sequential-adsorption-model-for-understanding-kinetics-of-proteins-adsorption-at-a-liquid-solid-interface
#16
Hwall Min, Eugene Freeman, Weiwei Zhang, Chowdhury Ashraf, David Allara, Adri C T van Duin, Srinivas Tadigadapa
In this Article, we experimentally measure the adsorption kinetics of human serum albumin (HSA) on a hydrophobic hexadecanethiolated gold surface. We use micromachined quartz crystal resonators with fundamental frequency of 83 MHz to accomplish these measurements in real time. In this work, we focus on two key results: (i) asymptotic behavior of the sensor responses upon HSA adsorption and (ii) the jamming limit of adsorbed layer formed by both single-injection and multi-injection experiments with the same value of final concentration...
July 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28637586/soluble-lr11-associates-with-aortic-root-calcification-in-asymptomatic-treated-male-patients-with-familial-hypercholesterolemia
#17
Ranitha Vongpromek, Sven Bos, Gert-Jan R Ten Kate, Hideaki Bujo, Meizi Jiang, Koen Nieman, Wolfgang Schneider, Jeanine E Roeters van Lennep, Adrie J M Verhoeven, Eric J G Sijbrands, Monique T Mulder
BACKGROUND AND AIMS: Despite statin treatment, a high prevalence of severe vascular calcification is found in patients with familial hypercholesterolemia (FH). We assessed the relation between the circulating soluble form of low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11), a risk factor for cardiovascular disease, and vascular calcification in asymptomatic statin-treated heterozygous FH patients. METHODS: In 123 asymptomatic heterozygous FH patients (age 40-69 years), aortic root (ARC), aortic valve (AVC) and coronary artery calcification (CAC) were determined with CT-based calcium scoring expressed in Agatston units...
June 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28618304/breast-magnetic-resonance-imaging-use-in-patients-undergoing-neoadjuvant-chemotherapy-is-associated-with-less-mastectomies-in-large-ductal-cancers-but-not-in-lobular-cancers
#18
Ingeborg J H Vriens, Kristien Keymeulen, Marc B I Lobbes, Annelotte C M van Bommel, Grard A P Nieuwenhuijzen, Marjolein L Smidt, Liesbeth J Boersma, Thijs van Dalen, Carolien H Smorenburg, Henk Struikmans, Sabine Siesling, Adri C Voogd, Vivianne C G Tjan-Heijnen
BACKGROUND: To assess the impact of breast magnetic resonance imaging (MRI) use on surgical outcome per histological breast cancer subtype in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: All patients aged 18-70 years who underwent neoadjuvant chemotherapy for stage I-III invasive breast cancer in the Netherlands in the years 2011-2013 were identified from the Netherlands Cancer Registry. Patients with cT4 tumours were excluded from the analysis...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28570806/second-generation-reaxff-water-force-field-improvements-in-the-description-of-water-density-and-oh-anion-diffusion
#19
Weiwei Zhang, Adri C T van Duin
Hydronium (H3O(+)) and hydroxide (OH(-)) ions have anomalously large diffusion constants in aqueous solutions due to their combination of vehicular and Grotthuss hopping diffusion mechanisms. An improvement of the ReaxFF reactive water force field on the basis of our first-generation water force field (water-2010) is presented to describe the proton transfer (PT) mechanisms of H3O(+) and OH(-) in water. Molecular dynamics simulation studies with the water-2017 force field support the Eigen-Zundel-Eigen mechanism for PT in acidic aqueous solution and reproduce the hypercoordinated solvation structure of the OH(-) in a basic environment...
June 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28542477/mycobacterium-tuberculosis-arrests-host-cycle-at-the-g1-s-transition-to-establish-long-term-infection
#20
Bridgette M Cumming, Md Aejazur Rahman, Dirk A Lamprecht, Kyle H Rohde, Vikram Saini, John H Adamson, David G Russell, Adrie J C Steyn
Signals modulating the production of Mycobacterium tuberculosis (Mtb) virulence factors essential for establishing long-term persistent infection are unknown. The WhiB3 redox regulator is known to regulate the production of Mtb virulence factors, however the mechanisms of this modulation are unknown. To advance our understanding of the mechanisms involved in WhiB3 regulation, we performed Mtb in vitro, intraphagosomal and infected host expression analyses. Our Mtb expression analyses in conjunction with extracellular flux analyses demonstrated that WhiB3 maintains bioenergetic homeostasis in response to available carbon sources found in vivo to establish Mtb infection...
May 2017: PLoS Pathogens
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