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https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#1
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28528366/cdk5-mediated-phosphorylation-dependent-ubiquitination-and-degradation-of-e3-ubiquitin-ligases-gp78-accelerates-neuronal-death-in-parkinson-s-disease
#2
Qingzhi Wang, Fengjuan Jiao, Pei Zhang, Jianguo Yan, Zheng Zhang, Feng He, Qian Zhang, Zexi Lv, Xiang Peng, Hongwei Cai, Bo Tian
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD...
May 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28528332/the-persistent-m%C3%A3-llerian-duct-syndrome-an-update-based-upon-a-personal-experience-of-157-cases
#3
Jean-Yves Picard, Richard L Cate, Chrystèle Racine, Nathalie Josso
Male sex differentiation is driven by 2 hormones, testosterone and anti-müllerian hormone (AMH), responsible for the regression of müllerian ducts in male fetuses. Mutations inactivating AMH or its receptor AMHRII lead to the persistent müllerian duct syndrome (PMDS) in otherwise normally virilized 46,XY males. Our objective was to review the clinical, anatomical, and molecular features of PMDS based upon a review of the literature and upon 157 personal cases. Three clinical presentations exist: bilateral cryptorchidism, unilateral cryptorchidism with contralateral hernia, and transverse testicular ectopia...
May 20, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28528309/maintenance-of-claudin-3-expression-and-the-barrier-functions-of-intercellular-junctions-in-parotid-acinar-cells-via-the-inhibition-of-src-signaling
#4
Megumi Yokoyama, Takanori Narita, Hajime Sakurai, Osamu Katsumata-Kato, Hiroshi Sugiya, Junko Fujita-Yoshigaki
OBJECTIVES: Salivary acinar and duct cells show different expression patterns of claudins, which may reflect their different functions. To study the role of claudins in saliva secretion, we examined alterations in the expression patterns of cell adhesion molecules in parotid glands of γ-irradiated rats and analyzed the influence of those changes on intercellular barrier function using primary cultures of parotid acinar cells. DESIGN: Rats were γ-irradiated with doses of 5, 15 or 20Gy, and expression levels of cell adhesion molecules were examined by immunoblotting analysis...
May 15, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#5
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#6
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28528264/baseline-and-longitudinal-variability-of-normal-tissue-uptake-values-of-18-f-fluorothymidine-pet-images
#7
Matthijs C F Cysouw, Gerbrand M Kramer, Virginie Frings, Adrianus J De Langen, Mariëlle J Wondergem, Laura M Kenny, Eric O Aboagye, Carsten Kobe, Jürgen Wolf, Otto S Hoekstra, Ronald Boellaard
PURPOSE: [(18)F]-fluorothymidine ([(18)F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution. METHODS: (18)F-FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated...
May 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#8
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28528184/synergistic-antitumor-effect-of-nvp-bez235-and-cape-on-mda-mb-231-breast-cancer-cells
#9
Samira Torki, Amin Soltani, Hedayatollah Shirzad, Nafiseh Esmaeil, Mahdi Ghatrehsamani
Triple negative breast cancer (TNBC) is the most lethal and aggressive kind of breast cancer. Studies with TNBC cells suggest that tumor environmental cytokines such as Transforming Growth Factor β1 (TGF-β1) have important roles in tumors fate. In the present study, we aimed to investigate, the effect of phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235 and Caffeic acid phenyl ester (CAPE) on TNBC cell line (MDA-MB-231), stimulated with TGF-β1 for 14days in vitro...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528168/human-keratinocyte-differentiation-requires-translational-control-by-the-eif2%C3%AE-kinase-gcn2
#10
Ann E Collier, Ronald C Wek, Dan F Spandau
Appropriate and sequential differentiation of keratinocytes is essential for all functions of the human epidermis. While transcriptional regulation has proven to be important for keratinocyte differentiation, little is known about the role of translational control. A key mechanism for modulating translation is through phosphorylation of the α subunit of eIF2. A family of different eIF2α kinases function in the integrative stress response to inhibit general protein synthesis coincident with preferential translation of select mRNAs that participate in stress alleviation...
May 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28528122/probdnf-inhibits-proliferation-migration-and-differentiation-of-mouse-neural-stem-cells
#11
Jia-Yi Li, Jia Liu, Nimshitha Pavathuparambil Abdul Manaph, Larisa Bobrovskaya, Xin-Fu Zhou
ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro...
May 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28527959/systemic-treatment-patterns-with-advanced-or-recurrent-non-small-cell-lung-cancer-in-japan-a-retrospective-hospital-administrative-database-study
#12
Feng Wang, Sari Mishina, Shinji Takai, T Kim Le, Kenya Ochi, Kotaro Funato, Shozo Matsuoka, Yuichiro Ohe
PURPOSE: Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. METHODS: This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed...
May 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527909/binding-assay-for-characterization-of-protein-kinase-inhibitors-possessing-sub-picomolar-to-sub-millimolar-affinity
#14
Hedi Sinijarv, Shanshan Wu, Taavi Ivan, Kaido Viht, Asko Uri
High demand for inhibitors regulating the activity of protein kinases has stimulated the quest for high throughput and reliable compound screening assays. Here we introduce a method applying a non-metal photoluminescent probe ARC-Lum(Fluo) for determination of dissociation constants of competitive inhibitors of protein kinases. Employing a single probe instead of a combination of antibody and fluorescent tracer makes the assay simpler, cheaper, and more accurate than several other inhibitor-screening technologies...
May 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#15
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28527849/role-of-piezo-channels-in-ultrasound-stimulated-dental-stem-cells
#16
Qianhua Gao, Paul R Cooper, A Damien Walmsley, Ben A Scheven
INTRODUCTION: Piezo1 and Piezo2 are mechanosensitive membrane ion channels. We hypothesized that Piezo proteins may play a role in transducing ultrasound-associated mechanical signals and activate downstream mitogen-activated protein kinase (MAPK) signaling processes in dental cells. In this study, the expression and role of Piezo channels were investigated in dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) after treatment with low-intensity pulsed ultrasound (LIPUS)...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28527827/in%C3%A2-vitro-bioconversion-of-chitin-to-pyruvate-with-thermophilic-enzymes
#17
Kohsuke Honda, Keisuke Kimura, Pham Huynh Ninh, Hironori Taniguchi, Kenji Okano, Hisao Ohtake
Chitin is the second most abundant organic compound on the planet and thus has been regarded as an alternative resource to petroleum feedstocks. One of the key challenges in the biological conversion of biomass-derived polysaccharides, such as cellulose and chitin, is to close the gap between optimum temperatures for enzymatic saccharification and microbial fermentation and to implement them in a single bioreactor. To address this issue, in the present study, we aimed to perform an in vitro, one-pot bioconversion of chitin to pyruvate, which is a precursor of a wide range of useful metabolites...
May 17, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28527826/metabolic-pathway-analysis-of-the-xylose-metabolizing-yeast-protoplast-fusant-zlyrhz7
#18
Jingping Ge, Renpeng Du, Gang Song, Yuhuan Zhang, Wenxiang Ping
Xylose is the second major fermentable sugar present in hard woods and herbs (after d-glucose). Therefore, efficient conversion of xylose to ethanol is essential for the commercialization of lignocellulosic ethanol, which may provide an ideal alternative to fossil fuels in the future. ZLYRHZ7 is a fusant produced by protoplast fusion between two different yeast species, Saccharomyces cerevisiae W5 and Candida shehatae 20335, which is able to utilize xylose to produce ethanol. To improve ethanol production and to quantitatively analyze metabolic pathway in ZLYRHZ7, we used high performance liquid chromatography (HPLC) to assess the utilization rates of xylose, xylitol, and xylulose, and to measure ethanol yields using xylose, xylitol, and xylulose as sole carbon sources...
May 17, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28527717/inhibition-of-the-lateral-habenular-camk%C3%A2-abolishes-naloxone-precipitated-conditioned-place-aversion-in-morphine-dependent-mice
#19
Jing Wang, Min Li, Ping Wang, Yunhong Zha, Zhi He, Zicheng Li
Addictive substances mediate positive and negative states promoting compulsive drug use. However, substrates for aversive effects of drugs are not fully understood. We found that inactivation of the lateral habenula (LHb) by microinjection of tetrodotoxin (TTX) abolished naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice. We also found that lateral habenular administration of KN-62, a specific inhibitor for calcium/calmodulin dependent protein kinase II (CaMKII), abolished naloxone-precipitated CPA in morphine-dependent mice...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28527703/sperm-oocyte-contact-induces-outside-in-signaling-via-pyk2-activation
#20
Huizhen Wang, Jinping Luo, Carol Carlton, Lynda K McGinnis, William H Kinsey
Fertilization is a multi-step process that begins with plasma membrane interactions that enable sperm - oocyte binding followed by fusion of the sperm and oocyte plasma membranes. Once membrane fusion has occurred, sperm incorporation involves actin remodeling events within the oocyte cortex that allow the sperm head to penetrate the cortical actin layer and gain access to the ooplasm. Despite the significance for reproduction, the control mechanisms involved in gamete binding, fusion, and sperm incorporation are poorly understood...
May 17, 2017: Developmental Biology
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