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https://www.readbyqxmd.com/read/28930981/generation-of-prostate-cancer-cell-models-of-resistance-to-the-anti-mitotic-agent-docetaxel
#1
Lisa Mohr, Marc Carceles-Cordon, Jungreem Woo, Carlos Cordon-Cardo, Josep Domingo-Domenech, Veronica Rodriguez-Bravo
Microtubule targeting agents (MTAs) are a mainstay in the treatment of a wide range of tumors. However, acquired resistance to chemotherapeutic drugs is a common mechanism of disease progression and a prognostic-determinant feature of malignant tumors. In prostate cancer (PC), resistance to MTAs such as the taxane Docetaxel dictates treatment failure as well as progression towards lethal stages of disease that are defined by a poor prognosis and high mortality rates. Though studied for decades, the array of mechanisms contributing to acquired resistance are not completely understood, and thus pose a significant limitation to the development of new therapeutic strategies that could benefit patients in these advanced stages of disease...
September 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28929762/modulating-the-performance-of-an-asymmetric-organocatalyst-by-tuning-its-spatial-environment-in-a-metal-organic-framework
#2
Lujia Liu, Tian-You Zhou, Shane G Telfer
Systematically tuning the spatial environment around the active sites of synthetic catalysts is a difficult challenge. Here, we show how this can be accomplished in the pores of multicomponent metal-organic frameworks. This relies on embedding a catalytic unit in a pore of the MUF-77 framework and then tuning its environment by introducing different functional groups to the surrounding linkers. This approach benefits from the structural regularity of MUF-77, which places each component in a precise location to circumvent disorder...
September 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28928132/seca-mediates-cotranslational-targeting-and-translocation-of-an-inner-membrane-protein
#3
Shuai Wang, Chien-I Yang, Shu-Ou Shan
Protein targeting to the bacterial plasma membrane was generally thought to occur via two major pathways: cotranslational targeting by signal recognition particle (SRP) and posttranslational targeting by SecA and SecB. Recently, SecA was found to also bind ribosomes near the nascent polypeptide exit tunnel, but the function of this SecA-ribosome contact remains unclear. In this study, we show that SecA cotranslationally recognizes the nascent chain of an inner membrane protein, RodZ, with high affinity and specificity...
September 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#4
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28923960/igh-isotype-specific-b-cell-receptor-expression-influences-b-cell-fate
#5
Pei Tong, Alessandra Granato, Teng Zuo, Neha Chaudhary, Adam Zuiani, Seung Seok Han, Rakesh Donthula, Akritee Shrestha, Debattama Sen, Jennifer M Magee, Michael P Gallagher, Cees E van der Poel, Michael C Carroll, Duane R Wesemann
Ig heavy chain (IgH) isotypes (e.g., IgM, IgG, and IgE) are generated as secreted/soluble antibodies (sIg) or as membrane-bound (mIg) B cell receptors (BCRs) through alternative RNA splicing. IgH isotype dictates soluble antibody function, but how mIg isotype influences B cell behavior is not well defined. We examined IgH isotype-specific BCR function by analyzing naturally switched B cells from wild-type mice, as well as by engineering polyclonal Ighγ1/γ1 and Ighε/ε mice, which initially produce IgG1 or IgE from their respective native genomic configurations...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923365/mitochondrial-dynamics-at-the-interface-of-immune-cell-metabolism-and-function
#6
REVIEW
Angelika S Rambold, Erika L Pearce
Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism...
September 8, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28922503/modulating-the-structural-properties-of-alpha-gamma-hybrid-peptides-by-alpha-amino-acid-residues-uniform-12-helix-versus-mixed-12-10-helix
#7
Rajkumar Misra, K Muruga Poopathi Raja, Hans-Jörg Hofmann, Hosahudya Gopi
The most important natural a- and 310-helices are stabilized by unidirectional intramolecular hydrogen bonds along the helical cylinder. In contrast, we are reporting here on 12/10-helical conformations with alternately changing H-bond directionality in sequences of alpha,gamma-hybrid peptides [P1: Boc-Ala-Aic-Ala-Aic-COOH; P2: Boc-Leu-Aic-Leu-Aic-OEt; P3: Boc-Leu-Aic-Leu-Aic-Leu-Aic-Aib-OMe; P4: Boc-Ala-Aic-Ala-Aic-Ala-Aic-Ala-OMe; P5: Boc-Leu-Aic-Leu-Aic-Leu-Aic-Leu-Aic-Aib-OMe] composed of natural a-amino acids and the achiral gamma4,4-dimethyl substituted g-amino acid Aic in solution and in single crystals...
September 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28921970/tris-heteroleptic-iridium-complexes-based-on-cyclometalated-ligands-with-different-cores
#8
Yanouk Cudré, Felipe Franco de Carvalho, Gregory R Burgess, Louise Male, Simon J A Pope, Ivano Tavernelli, Etienne Baranoff
A series of tris-heteroleptic iridium complexes of the form [Ir(C^N(1))(C^N(2))(acac)] combining 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (dFppy), 1-phenylpyrazole (ppz), and 1-(2,4-difluorophenyl)pyrazole (dFppz) as the C^N ligands have been synthesized and fully characterized by NMR, X-ray crystallography, UV-vis absorption and emission spectroscopy, and electrochemical methods. It is shown that "static properties" (e.g., absorption and emission spectra and redox potentials) are primarily dictated by the overall architecture of the complex, while "dynamic properties" (e...
September 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28919175/slow-ampar-synaptic-transmission-is-determined-by-stargazin-and-glutamate-transporters
#9
Hsin-Wei Lu, Timothy S Balmer, Gabriel E Romero, Laurence O Trussell
AMPARs mediate the briefest synaptic currents in the brain by virtue of their rapid gating kinetics. However, at the mossy fiber-to-unipolar brush cell synapse in the cerebellum, AMPAR-mediated EPSCs last for hundreds of milliseconds, and it has been proposed that this time course reflects slow diffusion from a complex synaptic space. We show that upon release of glutamate, synaptic AMPARs were desensitized by transmitter by >90%. As glutamate levels subsequently fell, recovery of transmission occurred due to the presence of the AMPAR accessory protein stargazin that enhances the AMPAR response to low levels of transmitter...
September 8, 2017: Neuron
https://www.readbyqxmd.com/read/28917985/the-effect-of-particle-shape-on-cellular-interaction-and-drug-delivery-applications-of-micro-and-nanoparticles
#10
REVIEW
Anil B Jindal
Encapsulation of therapeutic agents in nanoparticles offers several benefits including improved bioavailability, site specific delivery, reduced toxicity and in vivo stability of proteins and nucleotides over conventional delivery options. These benefits are consequence of distinct in vivo pharmacokinetic and biodistribution profile of nanoparticles, which is dictated by the complex interplay of size, surface charge and surface hydrophobicity. Recently, particle shape has been identified as a new physical parameter which has exerted tremendous impact on cellular uptake and biodistribution, thereby in vivo performance of nanoparticles...
September 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28916027/oral-leukoplakia-and-oral-cavity-squamous-cell-carcinoma
#11
Arnaud F Bewley, D Gregory Farwell
Oral leukoplakia is defined as a white oral lesion not related to another disease process. These lesions are largely asymptomatic, and the clinical relevance of oral leukoplakia is primarily tied to its association with oral cavity squamous cell carcinoma. Timely workup and effective management of these lesions can reduce the risk of malignant transformation and promote early diagnosis of invasive tumors. A biopsy should be performed promptly of any persistent or suspicious leukoplakia with subsequent management dictated by histologic findings...
September 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28915969/hyperglycemia-in-acute-ischemic-stroke-is-it-time-to-re-evaluate-our-understanding
#12
Rwoof Reshi, Chris Streib, Mustapha Ezzeddine, Michelle Biros, Benjamin Miller, Kamakshi Lakshminarayan, David Anderson, Agnieszka Ardelt
Among 700,000 new and recurrent ischemic stroke patients per year, forty percent are hyperglycemic on admission. In-vitro, hyperglycemia is toxic to neurons. Acute ischemic stroke patients who are hyperglycemic on admission experience higher morbidity and mortality. Results of multiple trials have provided no evidence supporting benefit in achieving normoglycemia. On the contrary, there is some evidence that tight glycemic control in acute brain injury is associated with poor outcome. Current consensus derived guidelines from the American Heart Association/American Stroke Association recommend an upper limit of blood glucose of 140-180mg/dl, as there is no evidence to support strict control...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28915047/two-photon-absorption-in-pentacene-dimers-the-importance-of-the-tether-using-upconversion-as-an-indirect-route-to-singlet-fission
#13
Eleonora Garoni, Johannes Zirzlmeier, Bettina S Basel, Constantin Hetzer, Kenji Kamada, Dirk M Guldi, Rik R Tykwinski
In this proof of concept study, we show that intramolecular singlet fission (iSF) can be initiated from a singlet excited state accessed by two-photon absorption, rather than through a tradition route of direct one-photon excitation (OPE). Thus, iSF in pentacene dimers 2 and 3 is enabled through NIR irradiation at 775 nm, a wavelength where neither dimer exhibits linear absorption of light. The meta-phenylene and adamantyl tethers 2 and 3, respectively, are designed to feature superimposable geometry, which establishes that the electronic coupling between the two pentacenes is the significant structural feature that dictates iSF efficiency...
September 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28913979/physical-pain-increases-interpersonal-trust-in-females
#14
C Wang, J Gao, Y Ma, C Zhu, X-W Dong
BACKGROUND: People behave and interact with others differently when experiencing physical pain. Pain has dramatic effects on one's emotional responses, cognitive functions and social interaction. However, little has been known about whether and how physical pain influences interpersonal trust in social interaction. In the present study, we examined the influence of physical pain on trusting behaviour. METHODS: A total of 112 healthy participants were recruited and assigned to physical pain condition (induced by Capsaicin) and control condition (with hand cream), respectively...
September 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28912559/inherent-aggressive-character-of-invasive-and-non-invasive-cells-dictates-the-in-vitro-migration-pattern-of-multicellular-spheroid
#15
Sukanya Gayan, Abhishek Teli, Tuli Dey
Cellular migration, a process relevant to metastasis, is mostly studied in the conventional 2D condition. However, cells cultured in the 3D condition assumed to mimic the in vivo conditions better. The current study is designed to compare an invasive and non-invasive adenocarcinoma cell with an invasive fibrosarcoma cell to understand the migration pattern of the multicellular spheroid. It is observed that conventional haplotaxis, chemotactic and pseudo-3D migration assay cannot distinguish between the invasive and non-invasive cells conclusively under 2D condition...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912510/the-th1-th17-balance-dictates-the-fibrosis-response-in-murine-radiation-induced-lung-disease
#16
Alexandra Paun, Marie-Eve Bergeron, Christina K Haston
Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains were exposed to 18 Gy whole thorax irradiation and upon respiratory distress strains prone to pneumonitis with fibrosis presented an increased pulmonary frequency of Thelper (Th)17 cells which was not evident in strains prone solely to pneumonitis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911172/androgens-mediate-sex-dependent-gonadotropin-expression-during-late-prenatal-development-in-the-mouse
#17
Michael J Kreisman, Christopher I Song, Kathleen Yip, Bryony V Natale, David R Natale, Kellie M Breen
Central organization of the hypothalamic-pituitary-gonadal axis is initiated during fetal life. At this critical time, gonadal hormones mediate sex-specific development of the hypothalamic-pituitary axis, which then dictates reproductive physiology and behavior in adulthood. Although studies have investigated the effects of prenatal androgens on central factors influencing gonadotropin-releasing hormone (GnRH) release, the impact of fetal androgens on gonadotrope function has been overlooked. In the current study, we demonstrated that gonadotropin gene expression and protein production were robustly elevated in female mice compared with males during late fetal development and that this sex difference was dependent on fetal androgens...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28911117/structure-based-domain-assignment-in-leishmania-infantum-endog-characterization-of-a-ph-dependent-regulatory-switch-and-a-c-terminal-extension-that-largely-dictates-dna-substrate-preferences
#18
Cristina Oliva, Pedro A Sánchez-Murcia, Eva Rico, Ana Bravo, Margarita Menéndez, Federico Gago, Antonio Jiménez-Ruiz
Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145-180 is indeed far more active than its wild-type counterpart at pH values >7...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910723/sorption-desorption-equilibrium-and-diffusion-of-tetracycline-in-poultry-litter-and-municipal-biosolids-soil-amendments
#19
E D'Angelo
Tetracycline (TET) is commonly used to treat bacterial diseases in humans and chickens (Gallus gallus domesticus), is largely excreted, and is found at elevated concentrations in treated sewage sludge (biosolids) and poultry litter (excrement plus bedding materials). Routine application of these nutrient-and carbon-enriched materials to soils improves fertility and other characteristics, but the presence of antibiotics (and other pharmaceuticals) in amendments raises questions about potential adverse effects on biota and development of antibiotic resistance in the environment...
September 8, 2017: Chemosphere
https://www.readbyqxmd.com/read/28905991/target-of-rapamycin-signaling-orchestrates-growth-defense-trade-offs-in-plants
#20
David De Vleesschauwer, Osvaldo Filipe, Gena Hoffman, Hamed Soren Seifi, Ashley Haeck, Patrick Canlas, Jonas Van Bockhaven, Evelien De Waele, Kristof Demeestere, Pamela Ronald, Monica Hofte
Plant defense to microbial pathogens is often accompanied by significant growth inhibition. How plants merge immune system function with normal growth and development is still poorly understood. Here, we investigated the role of target of rapamycin (TOR), an evolutionary conserved serine/threonine kinase, in the plant defense response. We used rice as a model system and applied a combination of chemical, genetic, genomic and cell-based analyses. We demonstrate that ectopic expression of TOR and Raptor (regulatory-associated protein of mTOR), a protein previously demonstrated to interact with TOR in Arabidopsis, positively regulates growth and development in rice...
September 14, 2017: New Phytologist
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