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101.
Mor I Bruck T Greenberg D Berson A Schreiber L Grisaru D Soreq H 《Chemico-biological interactions》2008,175(1-3):11-21
Tumorogenic transformation is a multifaceted cellular process involving combinatorial protein-protein interactions that modulate different cellular functions. Here, we report apparent involvement in two independent tumorogenic processes by distinct partner protein interactions of the stress-induced acetylcholinesterase AChE-R and N-AChE-R variants. Human testicular tumors showed elevated levels of N-terminally extended N-AChE-R compared with healthy tissue, indicating alternate promoter usage in the transformed cells. Two-hybrid screens demonstrate that the C-terminus common to both N-AChE-R and AChE-R interacts either with the glycolytic enzyme enolase or with the scaffold protein RACK1. In vitro, the AChE-R C-terminal peptide ARP elevated enolase's activity by 12%, suggesting physiological relevance for this interaction. Correspondingly, CHO cells expressing either human AChE-R or N-AChE-R but not AChE-S showed a 25% increase in cellular ATP levels, indicating metabolic significance for this upregulation of enolase activity. ATP levels could be reduced by AChE-targeted siRNA in CHO cells expressing AChE-R but not AChE-S, attributing this elevation to the AChE-R C-terminus. Additionally, transfected CHO cells expressing AChE-R but not N-AChE-R showed resistance to up to 60muM of the common chemotherapeutic agent, cis-platinum, indicating AChE-R involvement in another molecular pathway. cis-Platinum elevates the expression of the apoptosis-regulator p53-like protein, p73, which is inactivated by interaction with the scaffold protein RACK1. In co-transfected cells, AChE-R competed with endogenous RACK1 for p73 interaction. Moreover, AChE-R-transfected CHO cells presented higher levels than control cells of the pro-apoptotic TAp73 as well as the anti-apoptotic dominant negative DeltaNp73 protein, leading to an overall decrease in the proportion of pro-apoptotic p73. Together, these findings are compatible with the hypothesis that in cancer cells, both AChE-R and N-AChE-R elevate cellular ATP levels and that AChE-R modifies p73 gene expression by facilitating two independent cellular pathways, thus conferring both a selective metabolic advantage and a genotoxic resistance. 相似文献
102.
Deo SH Barlow MA Gonzalez L Yoshishige D Caffrey JL 《American journal of physiology. Heart and circulatory physiology》2008,294(2):H829-H838
Delta-opioid receptors (DORs) are associated with ischemic preconditioning and vagal transmission in the sinoatrial (SA) node and atria. Although functional studies suggested that DORs are prejunctional on parasympathetic nerve terminals, their precise location remains unconfirmed. DORs were colocalized in tissue slices and synaptosomes from the canine right atrium and SA node along with cholinergic and adrenergic markers, vesicular acetylcholine transporter (VAChT), and tyrosine hydroxylase (TH). Synapsin I immunofluorescence verified the neural character of tissue structures and isolated synaptosomes. Acetylcholine and norepinephrine measurements suggested the presence of both cholinergic and adrenergic synaptosomes. Fluorescent analysis of VAChT and TH signals indicated that >80% of the synapsin-positive synaptosomes were of cholinergic origin and <8% were adrenergic. DORs colocalized 75-85% with synapsin in tissue slices from both atria and SA node. The colocalization was equally strong (85%) for nodal synaptosomes but less so for atrial synaptosomes (57%). Colocalization between DOR and VAChT was 75-85% regardless of the source. Overlap between DOR and TH was uniformly low, ranging from 8% to 17%. Western blots with synaptosomal extracts confirmed two DOR-positive bands at molecular masses corresponding to those reported for DOR monomers and dimers. The abundance of DOR was greater in nodal synaptosomes than in atrial synaptosomes, largely attributable to a greater abundance of monomers in the SA node. The abundant nodal and atrial DORs predominantly associated with cholinergic nerve terminals support the hypothesis that prejunctional DORs regulate vagal transmission locally within the heart. 相似文献
103.
León LG Machín RP Rodríguez CM Ravelo JL Martín VS Padrón JM 《Bioorganic & medicinal chemistry letters》2008,18(19):5171-5173
A set of gamma-lactones alpha,beta-fused and beta,gamma-fused to carbocycles have been synthesized and evaluated for their in vitro antiproliferative activities using the human cancer cell lines SW1573 (lung), T-47D (breast) and WiDr (colon). The compounds are obtained by intramolecular ring closing metathesis of the corresponding dienes. Active compounds exhibited GI(50) values in the range 8-18 microM. A structure-activity relationship is also discussed. 相似文献
104.
Roberto López-Píriz Eva Solá-Linares Mercedes Rodriguez-Portugal Beatriz Malpica Idoia Díaz-Güemes Silvia Enciso Leticia Esteban-Tejeda Belén Cabal Juan José Granizo José Serafín Moya Ramón Torrecillas 《PloS one》2015,10(10)
ObjectivesThe aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss.MethodsMandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3) were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM). Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period.ResultsDuring experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48) at G3 coating, 0.57 (SD 0.36) at ZnO35 coating, 0.74 (SD 0.47) at G1n-Ag coating, and 1.29 (SD 0.45) at control abutments; and statistically significant differences (p<0.001) were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42).SignificanceAntimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression. 相似文献
105.
Leticia Avilés Gyan Harwood 《Ethology : formerly Zeitschrift fur Tierpsychologie》2012,118(12):1219-1229
Species are often classified in discrete categories, such as solitary, subsocial, social and eusocial based on broad qualitative features of their social systems. Often, however, species fall between categories or species within a category may differ from one another in ways that beg for a quantitative measure of their sociality level. Here, we propose such a quantitative measure in the form of an index that is based on three fundamental features of a social system: (1) the fraction of the life cycle that individuals remain in their social group, (2) the proportion of nests in a population that contain multiple vs. solitary individuals and (3) the proportion of adult members of a group that do not reproduce, but contribute to communal activities. These are measures that should be quantifiable in most social systems, with the first two reflecting the tendencies of individuals to live in groups as a result of philopatry, grouping tendencies and intraspecific tolerance, and the third potentially reflecting the tendencies of individuals to exhibit reproductive altruism. We argue that this index can serve not only as a way of ranking species along a sociality scale, but also as a means of determining how level of sociality correlates with other aspects of the biology of a group of organisms. We illustrate the calculation of this index for the cooperative social spiders and the African mole‐rats and use it to analyse how sex ratios and interfemale spacing correlate with level of sociality in spider species in the genus Anelosimus. 相似文献
106.
107.
Melissa Carrillo Suraj Pandey Juan Sanchez Moraima Noda Ishwor Poudyal Luis Aldama Tek Narsingh Malla Elin Claesson Weixiao Yuan Wahlgren Denisse Feliz Vukica Šrajer Michał Maj Leticia Castillon So Iwata Eriko Nango Rie Tanaka Tomoyuki Tanaka Luo Fangjia Marius Schmidt 《Structure (London, England : 1993)》2021,29(7):743-754.e4
108.
Eneko Axpe Tamara Lopez-Euba Ainara Castellanos-Rubio David Merida Jose Angel Garcia Leticia Plaza-Izurieta Nora Fernandez-Jimenez Fernando Plazaola Jose Ramon Bilbao 《PloS one》2014,9(1)
Positron annihilation lifetime spectroscopy (PALS) provides a direct measurement of the free volume void sizes in polymers and biological systems. This free volume is critical in explaining and understanding physical and mechanical properties of polymers. Moreover, PALS has been recently proposed as a potential tool in detecting cancer at early stages, probing the differences in the subnanometer scale free volume voids between cancerous/healthy skin samples of the same patient. Despite several investigations on free volume in complex cancerous tissues, no positron annihilation studies of living cancer cell cultures have been reported. We demonstrate that PALS can be applied to the study in human living 3D cell cultures. The technique is also capable to detect atomic scale changes in the size of the free volume voids due to the biological responses to TGF-β. PALS may be developed to characterize the effect of different culture conditions in the free volume voids of cells grown in vitro. 相似文献
109.
Arturo Martinez Francisco Guitián Roberto López-Píriz José F. Bartolomé Belén Cabal Leticia Esteban-Tejeda Ramón Torrecillas José S. Moya 《PloS one》2014,9(1)
The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression. 相似文献
110.
Claudiane V. Almeida Caio F.R. de Oliveira Edson L. dos Santos Helder F. dos Santos Edson C. Júnior Reinaldo Marchetto Leticia A. da Cruz Alda Maria T. Ferreira Valdirene M. Gomes Gabriel B. Taveira Bruna O. Costa Octávio L. Franco Marlon H. Cardoso Maria Lígia R. Macedo 《Biochimica et Biophysica Acta (BBA)/General Subjects》2021,1865(9):129937
BackgroundAntimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus.MethodsA physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations.ResultsRQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces.ConclusionsRQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application.General significanceThese results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces. 相似文献