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Triple a

Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
Diptarka Hait, Martin Head-Gordon
Dipole moments are a simple, global measure of the accuracy of the electron density of a polar molecule. Dipole moments also affect the interactions of a molecule with other molecules as well as electric fields. To directly assess the accuracy of modern density functionals for calculating dipole moments, we have developed a database of 200 benchmark dipole moments, using coupled cluster theory through triple excitations, extrapolated to the complete basis set limit. This new database is used to assess the performance of 88 popular or recently developed density functionals...
March 21, 2018: Journal of Chemical Theory and Computation
Philip A Powell, Olivia Wills, Gemma Reynolds, Kaisa Puustinen-Hopper, Jennifer Roberts
In this paper we explored the effects of exposure to images of the suffering and vulnerability of others on altruistic, trust-based, and reciprocated incentivized economic decisions, accounting for differences in participants' dispositional empathy and reported in-group trust for their recipient(s). This was done using a pictorial priming task, framed as a memory test, and a triadic economic game design. Using the largest experimental sample to date to explore this issue, our integrated analysis of two online experiments (total N = 519), found statistically consistent evidence that exposure to images of suffering and vulnerability (vs...
2018: PloS One
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
Zhijuan Chen, Lingbao Ai, Mam Y Mboge, Robert McKenna, Christopher J Frost, Coy D Heldermon, Susan C Frost
Human cell lines are an important resource for research, and are often used as in vitro models of human diseases. In response to the mandate that all cells should be authenticated, we discovered that the MDA-MB-231 cells that were in use in our lab, did not validate based on the alleles of 9 different markers (STR Profile). We had been using this line as a model of triple negative breast cancer (TNBC) that has the ability to form tumors in immuno-compromised mice. Based on marker analysis, these cells most closely resembled the MCF10A line, which are a near diploid and normal mammary epithelial line...
March 21, 2018: Cancer Biology & Therapy
Benjamin Richard, Richard Swanson, Gonzalo Izaguirre, Steven Thomas Olson
Heparin allosterically activates the anticoagulant serpin, antithrombin, by binding through a sequence-specific pentasaccharide and inducing activating conformational changes in the protein. Three basic residues of antithrombin, Lys114, Lys125 and Arg129, have been shown to be hotspots for binding the pentasaccharide, but the molecular basis for such hotspot binding has been unclear. To determine whether this results from cooperative interactions, we analyzed the effects of single, double and triple mutations of the hotspot residues on pentasaccharide binding and activation of antithrombin...
March 21, 2018: Biochemistry
Marie-Christine Bacchus-Montabonel
The formation of the building blocks of life and how they could survive under harsh astrophysical environments remains an open question of prebiotic chemistry. Effectively, ion bombardments or intense UV radiation may drive the destruction of prebiotic compounds. The possible role of sulfur in such processes is addressed here for the first time, by comparing directly proton-induced charge transfer for sulfur containing molecules and that for related COMs. The proton collision on mercaptoacetonitrile HSCH2C[triple bond, length as m-dash]N conformers has thus been investigated theoretically in a wide impact energy range modelling various astrophysical environments and compared to related COMs, namely HCN oligomers, in order to exhibit qualitative tendencies...
March 21, 2018: Physical Chemistry Chemical Physics: PCCP
Yun Tang, Zhen-Yuan Zhu, Yao Liu, Huiqing Sun, Qiao-Ying Song, Yongmin Zhang
An acid polysaccharide, named R-PL, was extracted from rose buds by hot water (80 °C) extraction and purified by Sephadex G-200. R-PL, extracted with a total yield of 1.90%, is a highly pure polysaccharide with a total sugar content of 92.51%. A single and symmetrically sharp peak in its high-performance gel-permeation chromatography (HPGPC) spectrum indicates that R-PL is a homogeneous polysaccharide with a molecular weight of 7.727 × 105 Da. Monosaccharide composition analysis shows that it consists of d-arabinose, d-xylose, d-glucose, d-galactose, d-galacturonic acid, and d-glucuronic acid with a molar ratio of 4...
March 21, 2018: Food & Function
Li Xu, Jia Liu, Qilong Zhang, Min Li, Jingchi Liao, Weifeng Kuang, Cansheng Zhu, Huan Yi, Fuhua Peng
Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, especially when two antifungal drugs are at sub-therapeutic doses. Methods In this study of induction therapy, all non-HIV-infected, non-transplant patients with a first episode of cryptococcal meningitis were divided into two groups. In group I, the patients received amphotericin B plus 5-flucytosine. In group II, in addition to amphotericin B and 5-flucytosine, the patients also received fluconazole...
March 21, 2018: Neurological Research
Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R Sanberg, Darrell Sawmiller, Jun Tan
Alzheimer's disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP...
January 1, 2018: Cell Transplantation
Andrew W Artenstein, Jennifer Friderici, Paul Visintainer
Introduction: Spinal epidural abscess (SEA), a highly morbid and potentially lethal deep tissue infection of the central nervous system has more than tripled in incidence over the past decade. Early recognition at the point of initial clinical presentation may prevent irreversible neurologic injury or other serious, adverse outcomes. To facilitate early recognition of SEA, we developed a predictive scoring model. Methods: Using data from a 10-year, retrospective, case-control study of adults presenting for care at a tertiary-care, regional, academic medical center, we used the Integrated Discrimination Improvement Index (IDI) to identify candidate discriminators and created a multivariable logistic regression model, refined based on p-value significance...
March 2018: Western Journal of Emergency Medicine
S L Scholz, I Cosgarea, D Süßkind, R Murali, I Möller, H Reis, S Leonardelli, B Schilling, T Schimming, E Hadaschik, C Franklin, A Paschen, A Sucker, K P Steuhl, D Schadendorf, H Westekemper, K G Griewank
BACKGROUND: Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas remain incompletely understood. METHODS: A large cohort of 63 conjunctival melanomas was screened for gene mutations known to be important in other melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with patient prognosis. RESULTS: Frequent mutations in genes activating the MAP kinase pathway were identified...
March 21, 2018: British Journal of Cancer
Jhajaira M Araujo, Andrea C Gomez, Alfredo Aguilar, Roberto Salgado, Justin M Balko, Leny Bravo, Franco Doimi, Denisse Bretel, Zaida Morante, Claudio Flores, Henry L Gomez, Joseph A Pinto
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells...
March 20, 2018: Scientific Reports
Daniele Giuffrida, Mariosimone Zoccali, Adriana Arigò, Francesco Cacciola, Coralia Osorio Roa, Paola Dugo, Luigi Mondello
An on-line method based on the coupling of supercritical fluid extraction and supercritical fluid chromatography with triple quadrupole mass spectrometry detection (SFESFCQqQ/MS) for the native carotenoids characterization and apocarotenoids detection in yellow tamarillo was developed for the first time; this is the first work reporting the application of this methodology for the apocarotenoids analysis in any matrix. An off-line liquid extraction (LE) and analysis by LC-PDA-MS, using both a conventional C30 (3 μm I...
March 17, 2018: Archives of Biochemistry and Biophysics
Jiuyan Chen, Shurui Cao, Ming Zhu, Cunxian Xi, Lei Zhang, Xianliang Li, Guomin Wang, Yuantao Zhou, Zhiqiong Chen
An adsorbent, consisting of silica-coated Fe3 O4 grafted graphene oxide and β-cyclodextrin (Fe3 O4 @SiO2 /GO/β-CD), which possessed the merits of antioxidation, superparamagnetism, high surface area, high supramolecular recognition and environment friendly, was successfully fabricated. Considering the synergy between β-CD and graphene oxide in adsorption mechanism, the synthesized adsorbent could grasp compounds especially with aromatic structures through π-π interaction, hydrophobic interaction and host-guest inclusion complex forming...
March 4, 2018: Journal of Chromatography. A
Odile Francesca Restaino, Maria Giovanna Borzacchiello, Ilaria Scognamiglio, Luigi Fedele, Alberto Alfano, Elena Porzio, Giuseppe Manco, Mario De Rosa, Chiara Schiraldi
BACKGROUND: Thermostable phosphotriesterase-like lactonases (PLLs) are able to degrade organophosphates and could be potentially employed as bioremediation tools and bioscavengers. But nowadays their manufacturing in high yields is still an issue that limits their industrial applications. In this work we aimed to set up a high yield production and purification biotechnological process of two recombinant PLLs expressed in E. coli, the wild type SacPox from Sulfolobus acidocaldarius and a triple mutated SsoPox C258L/I261F/W263A, originally from Sulfolobus solfataricus...
March 20, 2018: BMC Biotechnology
Narayan Balaji, Suresh P Sulochana, Neeraj Kumar Saini, Siva Kumar A, Ramesh Mullangi
A simple, selective and reliable LC-MS/MS method was developed and validated for the simultaneous quantitation of darolutamide diastereomers (diastereomer-1 and diastereomer-2) and its active metabolite i. e. ORM-15341 in mice plasma using warfarin as an internal standard (IS) as per the regulatory guidelines. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Chiralpak IA column with an isocratic mobile phase 5 mM ammonium acetate:absolute alcohol (20:80, v/v) at a flow rate of 1...
March 20, 2018: Drug Research
Zuzanna Podemska-Jedrzejczak, Agnieszka Malinska, Patrycja Sujka-Kordowska, Michal Nowicki, Mateusz Puslecki, Marek Jemielity, Bartlomiej Perek
The vascular endothelial growth factor (VEGF) family of peptides and caveolins (CAVs) are reported to contribute, in early graft failure in patients, a coronary artery bypass grafting (CABG). To investigate the possible association of ultimate luminal occlusion to VEGFs and CAVs expression, a functional analysis (based on the molecular biology, bioinformatics, histology, and clinical studies) was performed. Twenty-four hundred and sixty-eight CABG patients diagnosed with multivessel stable coronary artery disease (CAD) were enrolled into prospective study and assigned to two subgroups: double- and triple-vessel CAD subjects...
March 20, 2018: Heart and Vessels
Rajendra-Prasad Janapatla, Chyi-Liang Chen, Mei-Hua Hsu, Wan-Ting Liao, Cheng-Hsun Chiu
PURPOSE: Pneumococcal virulence protein-based vaccines can provide serotype-independent protection against pneumococcal infections. Many studies, including clinical observational studies on Thomsen-Friedenrich antigen exposure and haemolytic uremic syndrome, defined the role of neuraminidases NanA, NanB and NanC in host-pneumococcus interaction. Since neuraminidases are major virulence proteins, they are potential targets for both vaccines and small molecule inhibitors. Here we explored the utility of three neuraminidases as protein vaccine antigens to generate neutralizing antibodies and to increase survival following pneumococcal infections...
March 20, 2018: Journal of Medical Microbiology
Shih-Fan Lai, Yu-Hsuan Chen, Tony Hsiang-Kuang Liang, Che-Yu Hsu, Huang-Chun Lien, Yen-Sen Lu, Chiun-Sheng Huang, Sung-Hsin Kuo
INTRODUCTION: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation. METHODS: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed...
March 20, 2018: Journal of Neuro-oncology
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