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https://www.readbyqxmd.com/read/29352112/direct-cell-cell-contact-between-mature-osteoblasts-and-osteoclasts-dynamically-controls-their-functions-in-vivo
#1
Masayuki Furuya, Junichi Kikuta, Sayumi Fujimori, Shigeto Seno, Hiroki Maeda, Mai Shirazaki, Maki Uenaka, Hiroki Mizuno, Yoriko Iwamoto, Akito Morimoto, Kunihiko Hashimoto, Takeshi Ito, Yukihiro Isogai, Masafumi Kashii, Takashi Kaito, Shinsuke Ohba, Ung-Il Chung, Alexander C Lichtler, Kazuya Kikuchi, Hideo Matsuda, Hideki Yoshikawa, Masaru Ishii
Bone homeostasis is regulated by communication between bone-forming mature osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the spatial-temporal relationship and mode of interaction in vivo remain elusive. Here we show, by using an intravital imaging technique, that mOB and mOC functions are regulated via direct cell-cell contact between these cell types. The mOBs and mOCs mainly occupy discrete territories in the steady state, although direct cell-cell contact is detected in spatiotemporally limited areas...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29349513/3d-qsar-study-of-steroidal-and-azaheterocyclic-human-aromatase-inhibitors-using-quantitative-profile-of-protein-ligand-interactions
#2
Sehan Lee, Mace G Barron
Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency...
January 18, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29348817/a-mitochondrial-targeted-purine-based-hsp90-antagonist-for-leukemia-therapy
#3
Kelly G Bryant, Young Chan Chae, Rogelio L Martinez, John C Gordon, Khaled M Elokely, Andrew V Kossenkov, Steven Grant, Wayne E Childers, Magid Abou-Gharbia, Dario C Altieri
Reprogramming of mitochondrial functions sustains tumor growth and may provide therapeutic opportunities. Here, we targeted the protein folding environment in mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety, triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co-chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds, π-π stacking, cation-π contacts and hydrophobic interactions with the surrounding amino acids in the active site...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348537/radionuclides-transform-chemotherapeutics-into-phototherapeutics-for-precise-treatment-of-disseminated-cancer
#4
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29347563/importance-of-small-degree-nodes-in-assortative-networks-with-degree-weight-correlations
#5
Sijuan Ma, Ling Feng, Christopher Pineda Monterola, Choy Heng Lai
It has been known that assortative network structure plays an important role in spreading dynamics for unweighted networks. Yet its influence on weighted networks is not clear, in particular when weight is strongly correlated with the degrees of the nodes as we empirically observed in Twitter. Here we use the self-consistent probability method and revised nonperturbative heterogenous mean-field theory method to investigate this influence on both susceptible-infective-recovered (SIR) and susceptible-infective-susceptible (SIS) spreading dynamics...
October 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346400/the-mechanisms-how-heparin-affects-the-tumor-cell-induced-vegf-and-chemokine-release-from-platelets-to-attenuate-the-early-metastatic-niche-formation
#6
Jan Moritz Ponert, Svenja Schwarz, Reza Haschemi, Jens Müller, Bernd Pötzsch, Gerd Bendas, Martin Schlesinger
Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a direct interaction between platelets and MV3 melanoma or MCF7 breast cancer cells induces platelet activation and a VEGF release in citrated plasma that cannot be further elevated by the coagulation cascade and generated thrombin...
2018: PloS One
https://www.readbyqxmd.com/read/29345453/poly-glycidol-coating-on-ultrahigh-molecular-weight-polyethylene-for-reduced-biofilm-growth
#7
Jacob N Lockhart, Thomas J Spoonmore, Michael W McCurdy, Bridget R Rogers, Scott A Guelcher, Eva Harth
Semibranched poly(glycidol) (PG-OH) and poly(glycidol allylglycidyl ether) (PG-Allyl) coatings were formed on ultrahigh molecular weight polyethylene (UMWPE) in a unique two-step process which included radiation of UHMWPE followed by grafting of PG-OH or PG-Allyl to the surface via free radical cross-linking. Resulting surfaces were extensively characterized by FTIR-ATR, XPS, fluorescent microscopy, and contact goniometry. The performance was evaluated using the most prominent biofilm-forming bacteria Staphylococcus aureus for 24 and 48 h...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29340215/genome-stability-maintenance-in-naked-mole-rat
#8
I O Petruseva, A N Evdokimov, O I Lavrik
The naked mole-rat (Heterocephalus glaber) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest lived rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339803/carbohydrates-protect-protein-against-abiotic-fragmentation-by-soil-minerals
#9
Patrick N Reardon, Eric D Walter, Carrie L Marean-Reardon, Chad W Lawrence, Markus Kleber, Nancy M Washton
The degradation and turnover of soil organic matter is an important part of global carbon cycling and of particular importance with respect to attempts to predict the response of ecosystems to global climate change. Thus, it is important to mechanistically understand the processes by which organic matter can be degraded in the soil environment, including contact with reactive or catalytic mineral surfaces. We have characterized the outcome of the interaction of two minerals, birnessite and kaolinite, with two disaccharides, cellobiose and trehalose...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338637/selected-plant-essential-oils-and-their-main-active-components-a-promising-approach-to-inhibit-aflatoxigenic-fungi-and-aflatoxin-production-in-food
#10
José Vicente Gómez, Andrea Tarazona, Rufino Mateo-Castro, José Vicente Gimeno-Adelantado, Misericordia Jiménez, Eva M Mateo
Recent research has showed that Aspergillus flavus and Aspergillus parasiticus are aflatoxigenic species that can become very competitive in the framework of climate change. Aflatoxins show carcinogenic, mutagenic, immunotoxic and teratogenic effects on human and animals. Effective and sustainable measures to inhibit these species and aflatoxins in food are required. Origanum vulgare and Cinnamomum zeylanicum essential oils (EOs) and their major active constituents, carvacrol and cinnamaldehyde, respectively, were assayed for inhibiting these species and aflatoxin production in maize extract medium under different environmental conditions...
January 17, 2018: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/29336992/schwann-cell-lamellipodia-regulate-cell-cell-interactions-and-phagocytosis
#11
Johana Tello Velasquez, James A St John, Lynn Nazareth, Jenny A K Ekberg
Lamellipodia in Schwann cells (SCs) are crucial for myelination, but their other biological functions remain largely uncharacterised. Two types of lamellipodia exist in SCs: axial lamellipodia at the outermost edge of the cell processes, and radial lamellipodia appearing peripherally along the entire cell. We have previously shown that radial lamellipodia on olfactory glia (olfactory ensheathing cells; OECs) promote cell-cell adhesion, contact-mediated migration and phagocytosis. Here we have investigated whether lamellipodia in SCs have similar roles...
January 11, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29336441/a-high-pressure-study-of-calmodulin-ligand-interactions-using-small-angle-x-ray-and-elastic-incoherent-neutron-scattering
#12
Süleyman Cinar, Samy Al-Ayoubi, Christian Sternemann, Judith Peters, Roland Winter, Claus Czeslik
Calmodulin (CaM) is a Ca2+ sensor and mediates Ca2+ signaling through binding of numerous target ligands. The binding of ligands by Ca2+-saturated CaM (holo-CaM) is governed by attractive hydrophobic and electrostatic interactions that are weakened under high pressure in aqueous solutions. Moreover, the potential formation of void volumes upon ligand binding creates a further source of pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable to probe protein-ligand interactions. In this study, we compare the binding of two different ligands to holo-CaM as a function of pressure by using X-ray and neutron scattering techniques...
January 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29336303/keratinocytes-mediate-innocuous-and-noxious-touch-via-atp-p2x4-signaling
#13
Francie Moehring, Ashley M Cowie, Anthony D Menzel, Andy D Weyer, Michael Grzybowski, Thiago Arzua, Aron M Geurts, Oleg Palygin, Cheryl L Stucky
The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29335065/effects-of-maternal-marginal-iodine-deficiency-on-interactions-between-cerebellar-bergmann-glia-cells-and-purkinje-cells-in-rat-offspring
#14
Ye Yu, Jing Dong, Yuan Wang, Yi Wang, Hui Min, Zhong Yan Shan, Wei Ping Teng, Jie Chen
Iodine deficiency (ID) during early pregnancy has an adverse effect on children's psychomotor and motor function but the mechanism has not been clarified. Therefore, our aim was to study the effect of maternal marginal ID on cerebellar neurodevelopment and the underlying mechanism. After obtaining marginal ID rats, we examined interactions between Bergmann glia cells (BGs) and Purkinje cells (PCs) using immunofluorescence and expression of the glutamate transporter and receptor by western blot. Our results showed that marginal ID reduced the number of contacted points between BGs and PCs, and disturbed expression of the glutamate transporter and receptor...
December 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29330385/docking-thermodynamics-and-molecular-dynamics-md-studies-of-a-non-canonical-protease-inhibitor-mp-4-from-mucuna-pruriens
#15
Ashish Kumar, Harmeet Kaur, Abha Jain, Deepak T Nair, Dinakar M Salunke
Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens belongs to Kunitz-type protease inhibitor family. However, biochemical assays showed that this protein is a poor inhibitor of trypsin. To understand the basis of observed poor inhibition, thermodynamics and molecular dynamics (MD) simulation studies on binding of MP-4 to trypsin were carried out. Molecular dynamics simulations revealed that temperature influences the spectrum of conformations adopted by the loop regions in the MP-4 structure...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329077/nano-hydroxyapatite-blasted-titanium-surface-creates-a-biointerface-able-to-govern-src-dependent-osteoblast-metabolism-as-prerequisite-to-ecm-remodeling
#16
Célio J C Fernandes, Fábio Bezerra, Marcel R Ferreira, Amanda F C Andrade, Thais Silva Pinto, Willian F Zambuzzi
Over the last several years, we have focused on the importance of intracellular signaling pathways in dynamically governing the biointerface between pre-osteoblast and surface of biomaterial. Thus, this study investigates the molecular hallmarks involved in the pre-osteoblast relationship with different topography considering Machined (Mc), Dual Acid-Etching (DAE), and nano hydroxyapatite-blasted (nHA) groups. There was substantial differences in topography of titanium surface, considering Atomic Force Microscopy and water contact angle (Mc = 81...
December 28, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29326158/reciprocal-spatiotemporally-controlled-apoptosis-regulates-wolffian-duct-cloaca-fusion
#17
Masato Hoshi, Antoine Reginensi, Matthew S Joens, James A J Fitzpatrick, Helen McNeill, Sanjay Jain
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion...
January 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#18
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29319845/il-37-inhibits-il-4-il-13-induced-ccl11-production-and-lung-eosinophilia-in-murine-allergic-asthma
#19
Jiaoyan Lv, Yingluo Xiong, Wenjing Li, Xinyi Cui, Xunjia Cheng, Qibin Leng, Rui He
BACKGROUND: IL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model. METHODS: We examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29316206/inhibition-of-vegf-dependent-angiogenesis-and-tumor-angiogenesis-by-an-optimized-antibody-targeting-clec14a
#20
Taek-Keun Kim, Chang Sik Park, Jihye Jang, Mi Ra Kim, Hee-Jun Na, Kangseung Lee, Hyun Jung Kim, Kyun Heo, Byong Chul Yoo, Young-Myeong Kim, Je-Wook Lee, Su Jin Kim, Eun Sung Kim, Dae Young Kim, Kiweon Cha, Tae Gyu Lee, Sukmook Lee
The C-type lectin-like domain of CLEC14a (CLEC14a-CTLD) is a key domain that mediates endothelial cell-cell contacts in angiogenesis. However, the role of CLEC14a-CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity-determining region (CDR) grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti-angiogenic human monoclonal antibody that specifically targets CLEC14a-CTLD and that shows improved stability and homogeneity relative to the parental antibody...
January 9, 2018: Molecular Oncology
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