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https://www.readbyqxmd.com/read/28651225/developing-pyridazine-3-carboxamides-to-be-cb2-agonists-the-design-synthesis-structure-activity-relationships-and-docking-studies
#1
Hai-Yan Qian, Zhi-Long Wang, Xiao-Yu Xie, You-Lu Pan, Gang-Jian Li, Xin Xie, Jian-Zhong Chen
Herein, we described the design and synthesis of a series of pyridazine-3-carboxamides to be CB2-selective agonists via a combination of scaffold hopping and bioisosterism strategies. The compounds were subjected to assessment of their potential activities through calcium mobilization assays. Among the tested derivatives, more than half of these compounds exhibited moderate to potent CB2 agonist activity. Six compounds showed EC50 values below 35 nM, and several derivatives also exhibited significantly enhanced potency and high selectivity at the CB2 receptor over the CB1 receptor...
May 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28651180/does-a-short-term-exposure-to-atrazine-provoke-cellular-senescence-in-chlamydomonas-reinhardtii
#2
Marta Esperanza, Magali Houde, Marta Seoane, Ángeles Cid, Carmen Rioboo
The aim of this study was to investigate the impacts and modes of action of a chemical and nutrient deprivation on the cellular senescence process of Chlamydomonas reinhardtii. Several molecular and cellular parameters related to senescence phenomena were monitored in C. reinhardtii cells exposed for 24h to a sublethal concentration (0.25μM) of the herbicide atrazine and in unexposed 96h cells in an early stationary phase of growth. All endpoints showed the same pattern of response between treatments, except for the intracellular level of calcium, where a significant increase was observed in 24h-exposed cultures compared to 24h-log controls...
June 19, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28651163/ex-vivo-assessment-of-valve-thickness-calcification-of-patients-with-calcific-aortic-stenosis-in-relation-to-in-vivo-clinical-outcomes
#3
Ching-Li Cheng, Hsiao-Huang Chang, Pei-Jung Huang, Wei-Chen Wang, Shan-Yang Lin
Calcific aortic stenosis (AS) plays a critical role in the risk of cardiovascular disease. This preliminary study examined the relationship between the ex vivo valve thickness/calcification and in vivo clinical outcomes of Chinese patients with calcific AS. Six Chinese patients (3 patients with tricuspid aortic valves (TAV)) and 3 patients with. bicuspid aortic valves (BAV) with calcific AS undergoing heart valve replacement were initially chosen for this study. In vivo medical imaging of these calcific AS patients was evaluated using computed tomography and echocardiography...
June 22, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28650988/transcriptomic-analysis-to-uncover-genes-affecting-cold-resistance-in-the-chinese-honey-bee-apis-cerana-cerana
#4
Kai Xu, Qingsheng Niu, Huiting Zhao, Yali Du, Yusuo Jiang
The biological activity and geographical distribution of honey bees is strongly temperature-dependent, due to their ectothermic physiology. In China, the endemic Apis cerana cerana exhibits stronger cold hardiness than Western honey bees, making the former species important pollinators of winter-flowering plants. Although studies have examined behavioral and physiological mechanisms underlying cold resistance in bees, data are scarce regarding the exact molecular mechanisms. Here, we investigated gene expression in A...
2017: PloS One
https://www.readbyqxmd.com/read/28650787/the-effect-of-casein-phosphopeptide-amorf-calcium-phosphate-and-acidulated-phosphate-fluoride-gel-on-dental-erosion-in-primary-teeth-an-in-vitro-study
#5
Eda Arat Maden, Özge Acar, Ceyhan Altun, Günseli Güven Polat
OBJECTIVE: This study aimed to investigate the effect of acidulated phosphate fluoride (APF) gel and casein phosphopeptide/amorphous calciumphosphate (CPP-ACP) on the dental erosion produced by carbonated soft drink in primary teeth. STUDY DESIGN: This study evaluated by an in vitro model the effect of APF gel and CPP-ACP on the dental enamel previously subjected to erosive challenge with carbonated soft drink. Sixty sound human primary molars were prepared by embedding the crown sections in acrylic resin blocks leaving the enamel surfaces exposed...
2017: Journal of Clinical Pediatric Dentistry
https://www.readbyqxmd.com/read/28650461/a-light-and-calcium-gated-transcription-factor-for-imaging-and-manipulating-activated-neurons
#6
Wenjing Wang, Craig P Wildes, Tanyaporn Pattarabanjird, Mateo I Sanchez, Gordon F Glober, Gillian A Matthews, Kay M Tye, Alice Y Ting
Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene...
June 26, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28650460/a-calcium-and-light-gated-switch-to-induce-gene-expression-in-activated-neurons
#7
Dongmin Lee, Jung Ho Hyun, Kanghoon Jung, Patrick Hannan, Hyung-Bae Kwon
Despite recent advances in optogenetics, it remains challenging to manipulate gene expression in specific populations of neurons. We present a dual-protein switch system, Cal-Light, that translates neuronal-activity-mediated calcium signaling into gene expression in a light-dependent manner. In cultured neurons and brain slices, we show that Cal-Light drives expression of the reporter EGFP with high spatiotemporal resolution only in the presence of both blue light and calcium. Delivery of the Cal-Light components to the motor cortex of mice by viral vectors labels a subset of excitatory and inhibitory neurons related to learned lever-pressing behavior...
June 26, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28650391/proteins-differentially-expressed-in-the-pancreas-of-hepatic-alcohol-dehydrogenase-deficient-deer-mice-fed-ethanol-for-3-months
#8
Kamlesh K Bhopale, Samir M Amer, Lata Kaphalia, Kizhake V Soman, John E Wiktorowicz, Ghulam A Shakeel Ansari, Bhupendra S Kaphalia
OBJECTIVES: The aim of this study was to identify differentially expressed proteins in the pancreatic tissue of hepatic alcohol dehydrogenase-deficient deer mice fed ethanol to understand metabolic basis and mechanism of alcoholic chronic pancreatitis. METHODS: Mice were fed liquid diet containing 3.5 g% ethanol daily for 3 months, and differentially expressed pancreatic proteins were identified by protein separation using 2-dimensional gel electrophoresis and identification by mass spectrometry...
June 22, 2017: Pancreas
https://www.readbyqxmd.com/read/28650316/the-na-ca-2-k-exchanger-nckx4-is-required-for-efficient-cone-mediated-vision
#9
Frans Vinberg, Tian Wang, Alicia De Maria, Haiqing Zhao, Steven Bassnett, Jeannie Chen, Vladimir J Kefalov
Calcium (Ca(2+)) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca(2+) controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca(2+) in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na(+)/Ca(2+), K(+) exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650207/epicardial-pericardial-and-total-cardiac-fat-and-cardiovascular-disease-in-type-2-diabetic-patients-with-elevated-urinary-albumin-excretion-rate
#10
Regitse H Christensen, Bernt J von Scholten, Christian S Hansen, Sarah E Heywood, Jaya B Rosenmeier, Ulrik B Andersen, Peter Hovind, Henrik Reinhard, Hans-Henrik Parving, Bente K Pedersen, Marit E Jørgensen, Peter K Jacobsen, Peter Rossing
Background We evaluated the association of cardiac adipose tissue including epicardial adipose tissue and pericardial adipose tissue with incident cardiovascular disease and mortality, coronary artery calcium, carotid intima media thickness and inflammatory markers. Design A prospective study of 200 patients with type 2 diabetes and elevated urinary albumin excretion rate (UAER). Methods Cardiac adipose tissue was measured from baseline echocardiography. The composite endpoint comprised incident cardiovascular disease and all-cause mortality...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28650106/dok3-modulates-bone-remodeling-by-negatively-regulating-osteoclastogenesis-and-positively-regulating-osteoblastogenesis
#11
Xiaofeng Cai, Junjie Xing, Courtney L Long, Qisheng Peng, Mary Beth Humphrey
Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. RANKL promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis. Previously, we found that downstream of kinase-3 (DOK3) physically associates with DAP12 to inhibit toll-like receptor (TLR)-induced inflammatory signaling in macrophages...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28650087/educational-strategies-and-art-effect-on-salivary-characteristics-a-controlled-clinical-trial
#12
Camila Nobre de Freitas, Paula Midori Castelo, Karina Guedes de Sousa, Gabriela Caroline Alonso, Fernando Luiz Affonso Fonseca, Marlise Inês Klein, Taís de Souza Barbosa
OBJECTIVE: To evaluate educational strategies and ART-restoration impact on salivary physicochemical and microbiological characteristics. DESIGN: Two groups of 6-7-yr-old children were included: GART , with at least one decayed primary molar (n=36), submitted to 4 sessions of oral health educational strategy (OHES) and ART-restoration; GC , a paired caries-free group (n=36), submitted to 4 sessions of OHES. Three evaluations were carried out: baseline, one week after OHES and one month after OHES or ART, when biofilm and gingivitis frequencies, salivary flow, pH, buffer capacity, calcium and phosphorus concentrations were assessed...
June 26, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28649833/functional-prioritization-and-hydrogel-regulation-phenomena-created-by-a-combinatorial-pearl-associated-2-protein-biomineralization-model-system
#13
Gaurav Jain, Martin Pendola, Yu-Chieh Huang, Denis Gebauer, José Juan-Colás, Steven D Johnson, John Spencer Evans
In the nacre or aragonitic layer of the oyster pearl there exists a 12-member proteome which regulates both the early stages of nucleation and nano-to-mesoscale assembly of nacre tablets and calcitic crystals from mineral nanoparticle precursors. Several approaches have been developed to understand protein-associated mechanisms of pearl nacre formation, yet we still lack insight into how protein ensembles or proteomes manage nucleation and crystal growth. To provide additional insights we have created a proportionally-defined combinatorial model consisting of two pearl nacre-associated proteins, PFMG1 and PFMG2 (shell oyster pearl nacre, P...
June 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28649791/bioactivity-and-biomineralization-ability-of-calcium-silicate-based-pulp-capping-materials-after-subcutaneous-implantation
#14
G Hinata, K Yoshiba, L Han, N Edanami, N Yoshiba, T Okiji
AIM: To evaluate the abilities of three calcium silicate-based pulp-capping materials (ProRoot MTA, TheraCal LC, and a prototype tricalcium silicate cement) to produce apatite-like precipitates after being subcutaneously implanted into rats. METHODOLOGY: Polytetrafluoroethylene tubes containing each material were subcutaneously implanted into the backs of Wistar rats. At 7, 14, and 28 days post-implantation, the implants were removed together with the surrounding connective tissue, and fixed in 2...
June 26, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28649685/templated-and-self-limiting-calcite-formation-directed-by-coccolith-organic-macromolecules
#15
Assaf Gal, Richard Wirth, Zahava Barkay, Noam Eliaz, André Scheffel, Damien Faivre
The formation of intricately shaped crystalline minerals by organisms is orchestrated by specialized biomacromolecules. The macromolecules associated with coccoliths, nanometer-sized calcite crystal arrays produced by marine microalgae, can form a distinct calcium-rich phase via macromolecular recognition. Here, we show that this calcium-rich phase can be mineralized into a thin film of single-crystalline calcite by the balanced addition of carbonate ions. Such a crystallization process provides a strategy to direct crystalline products via local interactions between soluble macromolecules and compatible templates...
June 26, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28649639/initial-assessment-of-the-nutritional-quality-of-the-space-food-system-over-three-years-of-ambient-storage
#16
Maya Cooper, Michele Perchonok, Grace L Douglas
Processed and prepackaged space food is the main source of nutrition for crew aboard the International Space Station, and likely will continue to be the main source of nutrition for future exploration missions. However, very little information is available on the nutritional stability of space foods. To better understand their nutritional stability, 24 micronutrients were measured in 109 space foods stored over 3 years at room temperature. Our analysis indicated that potassium, calcium, vitamin D, and vitamin K concentrations in the food may not be adequate to meet the recommended daily intake requirements even before storage...
2017: NPJ Microgravity
https://www.readbyqxmd.com/read/28649635/gravireceptors-in-eukaryotes-a-comparison-of-case-studies-on-the-cellular-level
#17
Donat-P Häder, Markus Braun, Daniela Grimm, Ruth Hemmersbach
We have selected five evolutionary very different biological systems ranging from unicellular protists via algae and higher plants to human cells showing responses to the gravity vector of the Earth in order to compare their graviperception mechanisms. All these systems use a mass, which may either by a heavy statolith or the whole content of the cell heavier than the surrounding medium to operate on a gravireceptor either by exerting pressure or by pulling on a cytoskeletal element. In many cases the receptor seems to be a mechanosensitive ion channel activated by the gravitational force which allows a gated ion flux across the membrane when activated...
2017: NPJ Microgravity
https://www.readbyqxmd.com/read/28649259/the-cbl-and-cipk-gene-family-in-grapevine-vitis-vinifera-genome-wide-analysis-and-expression-profiles-in-response-to-various-abiotic-stresses
#18
Yue Xi, Jinyi Liu, Chao Dong, Zong-Ming Max Cheng
Calcium plays a central role in regulating signal transduction pathways. Calcineurin B-like proteins (CBLs), which harbor a crucial region consisting of EF hands that capture Ca(2+), interact in a specific manner with CBL-interacting protein kinases (CIPKs). This two gene families or their interacting-complex widely respond to various environment stimuli and development processes. The genome-wide annotation and specific expression patterns of CBLs and CIPKs, however, in grapevine remain unclear. In the present study, eight CBL and 20 CIPK genes were identified in grapevine genome, and divided into four and five subfamilies, respectively, based on phylogenetic analysis, and validated by gene structure and the distribution of conserved protein motifs...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28649232/ion-channels-of-pituitary-gonadotrophs-and-their-roles-in-signaling-and-secretion
#19
REVIEW
Stanko S Stojilkovic, Ivana Bjelobaba, Hana Zemkova
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28649222/highly-selective-cyclooxygenase-1-inhibitors-p6-and-mofezolac-counteract-inflammatory-state-both-in-vitro-and-in-vivo-models-of-neuroinflammation
#20
Rosa Calvello, Dario Domenico Lofrumento, Maria Grazia Perrone, Antonia Cianciulli, Rosaria Salvatore, Paola Vitale, Francesco De Nuccio, Laura Giannotti, Giuseppe Nicolardi, Maria Antonietta Panaro, Antonio Scilimati
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models...
2017: Frontiers in Neurology
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