bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo biocompatibility, vascularization, and incorporation of Integra® dermal regenerative template and flowable wound matrix
Authors: Später Thomas , Frueh Florian S. , Metzger Wolfgang , Menger Michael D. , Laschke Matthias W. 
Published: November 2016

AbstractIntegra® matrix wound dressing (MWD) is used for the reconstruction of full‐thickness skin defects. For the treatment of complex wounds, this dermal substitute is available as a flowable wound matrix (FWM) of identical composition. To clarify whether variations in sample preparation and consistency affect the biocompatibility and tissue incorporation, we herein compared MWD and FWM. The matrices were characterized using scanning electron microscopy and histology. Moreover, they were implanted in mouse dorsal skinfold chambers to analyze their in vivo performance over 2 weeks. Scanning electron microscopy showed a planar surface of MWD whereas FWM presented an irregular, fissured morphology. However, histology of the two matrices revealed an identical fiber thickness, fiber length, and interfiber distance. Repetitive stereo‐microscopy and immunohistochemical analyses of MWD and FWM showed a comparable epithelialization of the implants in the dorsal skinfold chamber model. At day 14, both matrices exhibited a low collagen content and microvessel density. Moreover, they were infiltrated by a high number of myeloperoxidase (MPO)‐positive neutrophilic granulocytes and a lower number of MAC387‐positive macrophages and CD3‐positive lymphocytes. These findings demonstrate that differences in preparation and consistency do not affect the tissue response to MWD and FWM, indicating a comparable regenerative capacity in wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 52–60, 2018.
Gene Expression and Activity Profiling Reveal a Significant Contribution of Exo‐Phosphotransferases to the Extracellular Nucleotides Metabolism in HUVEC Endothelial Cells
Authors: Wujak Magdalena , Hetmann Anna , Porowińska Dorota , Roszek Katarzyna 
Published: November 2016

ABSTRACTPurinergic signaling maintains local tissue homeostasis in blood vessels via the regulation of vascular tone, blood platelet aggregation, cell proliferation, and differentiation as well as inflammatory responses. Extracellular purines are important signaling molecules in the vasculature, and both purine‐hydrolysing as well as ‐phosphorylating enzymes are considered to selectively govern extracellular nucleotide/nucleoside metabolism. Recent studies have provided some evidence for the existence of these enzymes in a soluble form in human blood and their secretion into the extracellular space under physiological and pathological conditions. However, the comprehensive analysis of endothelium‐derived enzymes involved in purine metabolic pathways has received no attention so far. In the presented study, in vitro cultured human umbilical vein endothelial cells (HUVEC) are shown to be an abundant source of exo‐nucleotidases comprising 5′‐nucleotidase (exo‐5′‐NT), and nucleoside triphosphate diphosphohydrolases (exo‐NTPDase) as well as phosphotransferases, represented by nucleoside diphosphate kinase (exo‐NDPK) and adenylate kinase (exo‐AK). An attempt is also made to demonstrate that, in contrast to the metabolic pattern determined on the endothelial cell surface, exo‐phosphorylating activities markedly predominate over exo‐hydrolytic ones. We present for the first time the expression profiles of genes encoding isoenzymes belonging to distinct nucleotide kinase and nucleotidase families. The genes encoding NDPK1, NDPK2, AK1, and AK2 phosphotransferases have been shown to be expressed at the highest level in HUVEC cells. The data indicate the coexistence of secreted and cell‐associated factors of endothelial origin mediating ATP‐consuming and ATP‐generating pathways with the predominance of exo‐phosphotransferases activity. The described enzymes contribute to the regulation of purinergic signal duration and extent in the venous vasculature. J. Cell. Biochem. 118: 1341–1348, 2017. © 2016 Wiley Periodicals, Inc.
Genome‐Wide Transcriptome Profiling of the Neoplastic Giant Cell Tumor of Bone Stromal Cells by RNA Sequencing
Authors: Lau Carol P.Y. , Kwok Jamie S.L. , Tsui Joseph C.C. , Huang Lin , Yang Kevin Y. , Tsui Stephen K.W. , Kumta Shekhar Madhukar 
Published: November 2016

ABSTRACTGiant cell tumor of bone (GCTB) is the most common non‐malignant primary bone tumor reported in Hong Kong. Failure of treatment in advanced GCTB with aggressive local recurrence remains a clinical challenge. In order to reveal the molecular mechanism underlying the pathogenesis of this tumor, we aimed to examine the transcriptome profiling of the neoplastic stromal cells of GCTB in this study. RNA‐sequencing was performed on three GCTB stromal cell samples and one bone marrow‐derived MSC sample and 174 differentially expressed genes (DEGs) were identified between these two cell types. The top five up‐regulated genes are SPP1, F3, TSPAN12, MMP13, and LGALS3BP and further validated by qPCR and Western Blotting. Knockdown of SPP1 was found to induce RUNX2 and OPG expression in GCTB stromal cells but not the MSCs. Ingenuity pathway analysis (IPA) of the 174 DEGs revealed significant alternations in 23 pathways; variant calling analysis revealed 1915 somatic variants of 384 genes with high or moderate impacts. Interestingly, four canonical pathways were found overlapping in both analyses; from which VEGFA, CSF1, PLAUR, and F3 genes with somatic mutation were found up‐regulated in GCTB stromal cells. The STRING diagram showed two main clusters of the DEGs; one cluster of histone genes that are down‐regulated in GCTB samples and another related to osteoblast differentiation, angiogenesis, cell cycle progression, and tumor growth. The DEGs and somatic mutations found in our study warrant further investigation and validation, nevertheless, our study add new insights in the search for new therapeutic targets in treating GCTB. J. Cell. Biochem. 118: 1349–1360, 2017. © 2016 Wiley Periodicals, Inc.
The “Mechanostat” Principle and the Osteoprotegerin—OPG/RANKL/RANK System PART II. The Role of the Hypothalamic—Pituitary Axis
Authors: Tyrovola Joanna B. 
Published: November 2016

ABSTRACTRecent literature provides us with the indication that the ratio of OPG/RANKL concentrations fluctuate in a non‐linear (bell‐shaped) mode, according to Frost's “mechanostat” theory, during the application of mechanical strain. A similar cellular signal transduction mechanism to mechanical loading, that may also regulate bone resorptive activities, has nowdays been proposed. Since the skeleton is considered to be an endocrine organ, as such, it may likewise be subject to hypothalamic control. This central regulatory system may continually modulate the adaptation of the bone homeostatic system to external challenges. The hypothalamic‐pituitary‐gonadal axis may play a role in the regulation of OPG/RANKL secretion. The “mechanostat” principle may well characterize the oscillatory properties of the signal transduction mechanism that controls hard tissue metabolism and includes biochemical apart from mechanical stimuli. J. Cell. Biochem. 118: 962–966, 2017. © 2016 Wiley Periodicals, Inc.
Escalating Methamphetamine Regimen Induces Compensatory Mechanisms, Mitochondrial Biogenesis, and GDNF Expression, in Substantia Nigra
Authors: Valian Neda , Ahmadiani Abolhassan , Dargahi Leila 
Published: November 2016

ABSTRACTMethamphetamine (MA) produces long‐lasting deficits in dopaminergic neurons in the long‐term use via several neurotoxic mechanisms. The effects of MA on mitochondrial biogenesis is less studied currently. So, we evaluated the effects of repeated escalating MA regimen on transcriptional factors involved in mitochondrial biogenesis and glial‐derived neurotrophic factor (GDNF) expression in substantia nigra (SN) and striatum of rat. In male Wistar rats, increasing doses of MA (1–14 mg/kg) were administrated twice a day for 14 days. At the 1st, 14th, 28th, and 60th days after MA discontinuation, we measured the PGC1α, TFAM and NRF1 mRNA levels, indicator of mitochondrial biogenesis, and GDNF expression in SN and striatum. Furthermore, we evaluated the glial fibrillary acidic protein (GFAP) and Iba1 mRNA levels, and the levels of tyrosine hydroxylase (TH) and α‐synuclein (α‐syn) using immunohistochemistry and real‐time polymerase chain reaction (PCR). We detected increments in PGC1α and TFAM mRNA levels in SN, but not striatum, and elevations in GDNF levels in SN immediately after MA discontinuation. We also observed increases in GFAP and Iba1 mRNA levels in SN on day 1 and increases in Iba1 mRNA on days 1 and 14 in striatum. Data analysis revealed that the number of TH+ cells in the SN did not reduce in any time points, though TH mRNA levels was increased on day 1 after MA discontinuation in SN. These data show that repeated escalating MA induces several compensatory mechanisms, such as mitochondrial biogenesis and elevation in GDNF in SN. These mechanisms can reverse MA‐induced neuroinflammation and prevent TH‐immunoreactivity reduction in nigrostriatal pathway. J. Cell. Biochem. 118: 1369–1378, 2017. © 2016 Wiley Periodicals, Inc.
Impact of Target‐Mediated Elimination on the Dose and Regimen of Evolocumab, a Human Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Authors: Gibbs John P. , Doshi Sameer , Kuchimanchi Mita , Grover Anita , Emery Maurice G. , Dodds Michael G. , Gibbs Megan A. , Somaratne Ransi , Wasserman Scott M. , Blom Dirk 
Published: November 2016

AbstractUnderstanding the pharmacokinetic (PK) and pharmacodynamic (PD) relationship of a therapeutic monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibiting target‐mediated drug disposition (TMDD) is critical for selecting optimal dosing regimens. We describe the PK/PD relationship of evolocumab using a mathematical model that captures evolocumab binding and removal of unbound PCSK9 as well as reduction in circulating low‐density lipoprotein cholesterol (LDL‐C). Data were pooled from 2 clinical studies: a single‐dose escalation study in healthy subjects (7‐420 mg SC; n = 44) and a multiple‐dose escalation study in statin‐treated hypercholesterolemic patients (14 mg weekly to 420 mg monthly [QM] SC; n = 57). A TMDD model described the time course of unbound evolocumab concentrations and removal of unbound PCSK9. The estimated linear clearance and volume of evolocumab were 0.256 L/day and 2.66 L, respectively, consistent with other monoclonal antibodies. The time course of LDL‐C reduction was described by an indirect response model with the elimination rate of LDL‐C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with half‐maximal inhibition (IC50) of LDL‐C elimination was 1.46 nM. Based on simulations, 140 mg every 2 weeks (Q2W) and 420 mg QM were predicted to achieve a similar time‐averaged effect of 69% reduction in LDL‐C in patients on statin therapy, suggesting that an approximate 3‐fold dose increase is required for a 2‐fold extension in the dosing interval. Evolocumab dosing regimens of 140 mg Q2W or 420 mg QM were predicted to result in comparable reductions in LDL‐C over a monthly period, consistent with results from recently completed phase 3 studies.
The influence of very small doses of alpha radiation on the stability of erythrocytes
Authors: Kaczmarska Magdalena , Żydek Dominika , Wilkłacz‐Potoczny Justyna , Fornal Maria , Grodzicki Tomasz , Kochowska Elżbieta , Kozak Krzysztof , Gocal Łukasz , Pohorecki Władysław , Matlak Krzysztof , Korecki Józef , Burda Květoslava 
Published: November 2016

AbstractOur aim was to study the influence of low doses (0.2–4 μGy) of α radiation on the stability of human erythrocytes isolated from healthy and diabetic erythrocytes. Absorption spectroscopy was used to measure the level of red blood cell (RBC) hemolysis, along with Mössbauer spectroscopy, which is a highly specific method suited to monitoring various hemoglobin forms. States of hemoglobin are sensitive to a homeostatic imbalance in red blood cells. Changes in the membrane skeleton organization of irradiated erythrocytes isolated from healthy donors were studied using atomic force microscopy (AFM). Hemolysis, in healthy red blood cells, showed characteristic discontinuities, depending on the α particle flux and the exposure time to the low doses applied. This phenomenon was not observed in severe diabetic cases, which could be a result of modified protein–lipid–sugar complexes and the attenuation/absence of some antioxidative enzymatic processes in their RBC membranes. Similar effects were also observed for red blood cells treated with low doses of neutron and γ‐radiation. AFM measurements demonstrated a reorganization of the RBC membrane skeleton network depending on the time of RBC exposure to α radiation. This suggests that the changes in the activity of the acute defense processes against free radicals which are activated within the erythrocyte membrane irradiated with α‐particles could additionally be up‐ or down regulated by modifications to the membrane–skeleton network. However, even the highest dose of α radiation applied in these studies did not cause any significant changes in the ability of hemoglobin to transport oxygen. Microsc. Res. Tech. 80:131–143, 2017. © 2016 Wiley Periodicals, Inc.
Morphological changes induced in erythrocyte membrane by the antiepileptic treatment: An atomic force microscopy study
Authors: Oprisan Bogdan , Stoica Iuliana , Avadanei Mihaela Iuliana 
Published: November 2016

AbstractAtomic force microscopy (AFM), a powerful characterization tool widely applied in problems in a large range of disciplines of the natural sciences, including cellular biology, was used to obtain information about the morphological changes induced in the erythrocyte membrane at the patients with epilepsy that undergo a long time treatment that operates upon one or several neuronal ionic channels, comparative with a healthy donor. This technique allowed non‐invasive imaging of erythrocyte membrane, revealing details and specific characteristics down to the nanometer level with characterization of surface texture parameters, such as average height, average roughness and coefficient of kurtosis at micrometer/nanometer resolution. For the healthy donor the AFM morphology appears to have all the characteristics of a normal red blood cell membrane. Instead, the closer examination of the erythrocytes membrane surface morphology for the samples collected from the patients diagnosed with epilepsy and treated with specific drugs did not reveal similar structures with those obtained for the healthy donor. The nanostructure of the membrane was drastically damaged, depending on the administrated treatment, and probably in time will affect their functionality. Therefore, the anticomital drugs have influence not only at the neuronal level, but also at the red blood cell level.
The antiviral cytokine interferon‐gamma restricts neural stem/progenitor cell proliferation through activation of STAT1 and modulation of retinoblastoma protein phosphorylation
Authors: Kulkarni Apurva , Scully Taylor J. , O'Donnell Lauren A. 
Published: November 2016

AbstractNeural stem/progenitor cells (NPSCs) express receptors for many inflammatory cytokines, with varying effects on differentiation and proliferation depending on the stage of development and the milieu of inflammatory mediators. In primary neurons and astrocytes, we recently showed that interferon gamma (IFNγ), a potent antiviral cytokine that is required for the control and clearance of many central nervous system (CNS) infections, could differentially affect cell survival and cell cycle progression depending upon the cell type and the profile of activated intracellular signaling molecules. Here, we show that IFNγ inhibits proliferation of primary NSPCs through dephosphorylation of the tumor suppressor Retinoblastoma protein (pRb), which is dependent on activation of signal transducers and activators of transcription‐1 (STAT1) signaling pathways. Our results show i) IFNγ inhibits neurosphere growth and proliferation rate in a dose‐dependent manner; ii) IFNγ blocks cell cycle progression through a late‐stage G1/S phase restriction; iii) IFNγ induces phosphorylation and expression of STAT1 and STAT3; iv) IFNγ decreases cyclin E/cdk2 expression and reduces phosphorylation of cyclin D1 and pRb on serine residue 795; and v) the effects of IFNγ on NSPC proliferation, cell cycle protein expression, and pRb phosphorylation are STAT1‐dependent. These data define a mechanism by which IFNγ could contribute to a reduction in NSPC proliferation in inflammatory conditions. Further delineation of the effects of inflammatory cytokines on NSPC growth could improve our understanding of how CNS infections and other inflammatory events disrupt brain development and NSPC function. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Simulation and fabrication of a fast fringe‐field switching liquid crystal with enhanced surface anchoring enabled by controlled polymer topology
Authors: Weng Libo , Varanytsia Andrii , Chang Kai‐Han , Chien Liang‐Chy 
Published: November 2016

AbstractWe demonstrate a fringe‐field switching nematic liquid crystal with electro‐optical behavior modulated by both bulk and surface polymer stabilization. The polymer is formed by ultraviolet irradiation‐induced phase separation of various amounts of a reactive monomer in the planar‐aligned nematic liquid crystal. Simulation is carried out to verify the effect of anchoring energy. Experimental evidence validates the effect of monomer concentration on transmittance–voltage and response times curves of fringe‐field switching cells. The polymer‐stabilized alignment with a higher polymer concentration escalates the interaction between the liquid crystal and the polymer structure and increases the surface anchoring energy. The polymer stabilization also improves the dynamic response times of liquid crystal. The enabling polymer‐stabilized alignment technique has excellent electro‐optical properties such as a very good dark state, high optical contrast, and fast rise and decay times that may lead to development of a wide range of applications.
Hearing loss associated with enlarged vestibular aqueduct and zero or one mutant allele of SLC26A4
Authors: Rose Jane , Muskett Julie A. , King Kelly A. , Zalewski Christopher K. , Chattaraj Parna , Butman John A. , Kenna Margaret A. , Chien Wade W. , Brewer Carmen C. , Griffith Andrew J. 
Published: November 2016

Objectives/HypothesisTo characterize the severity and natural history of hearing loss, and the prevalence of having a cochlear implant in a maturing cohort of individuals with enlarged vestibular aqueduct (EVA) and zero or one mutant allele of SLC26A4.Study DesignProspective cohort study of subjects ascertained between 1998 and 2015 at the National Institutes of Health Clinical Center.MethodsStudy subjects were 127 individuals (median age, 8 years; range, 0–59 years) with EVA in at least one ear.ResultsEars with EVA and zero or one mutant allele of SLC26A4 had mean 0.5/1/2/4‐kHz pure‐tone averages of 62.6 and 52.9 dB HL, respectively, in contrast to EVA ears with two mutant alleles of SLC26A4 (88.1 dB HL; P < .01). This association was independent of age, sex, or side of EVA (P < .001). Natural history of hearing loss was not associated with number of mutant alleles (P = .94). The prevalence of having a cochlear implant was nine (12%) of 76, two (13%) of 15, and 12 (38%) of 32 subjects with zero, one, and two mutant alleles, respectively (P = .00833). This association was not independent (P = .534) but reflected underlying correlations with age at time of first audiogram (P = .003) or severity of hearing loss (P = .000).ConclusionsEars with EVA and zero or one mutant allele of SLC26A4 have less severe hearing loss, no difference in prevalence of fluctuation, and a lower prevalence of cochlear implantation in comparison to ears with two mutant alleles of SLC26A4.Level of EvidenceNA Laryngoscope, 127:E238–E243, 2017
Predator driven changes in prey size distribution stabilize secondary production in lacustrine food webs
Authors: Detmer Thomas M. , McCutchan James H. , Lewis William M. 
Published: November 2016

AbstractData from 12 Colorado mountain lakes, some containing invertivorous fish and some without fish, show that fish suppressed biomass of benthic invertebrates and zooplankton and reduced their mean and maximum body size, but did not alter invertebrate production. Resilience of invertebrate production occurred because the smaller body size of invertebrates in lakes with fish raised the community P/B ratio and simultaneously caused an increase in abundance of small invertebrates (<10 mm benthic invertebrates; < 1.5 mm zooplankton), probably by releasing small invertebrates from competition with large invertebrates. Together, these two changes in the invertebrate communities stabilized secondary production even though total invertebrate biomass was reduced. Compensatory stability of herbivore production in response to size selective predation by fish may be a common phenomenon in aquatic food webs. Because it involves both an increase in P/B ratio and an increase in biomass of invertebrates with high P/B ratio, compensation may to some degree explain the commonly observed failure of predation pressure by primary consumers to cause an increase in biomass of primary producers for trophic cascades with three levels, even when invertebrate biomass is reduced by predation. Addition of a fourth trophic level consisting of piscivorous fish would likely have less predictable effects because piscivores produce offspring that are invertivorous predators, thus potentially adding a qualitatively different compensatory mechanism to the trophic cascade.
Rabbit model of tracheal stenosis using cylindrical diffuser
Authors: Lee Hyoung Shin , Kim Sung Won , Oak Chulho , Kang Hyun Wook , Oh Junghwan , Jung Min Jung , Kim Sung Bin , Won Jun Hee , Lee Kang Dae 
Published: November 2016

Background and ObjectiveVariable methods of animal model have been introduced to develop tracheal stenosis. However, none of the prior models allow for predictable determination of the grade of stenosis. This study sought to establish an animal model of tracheal stenosis by using a cylindrical diffuser and to evaluate the feasibility of a reproducible model.Study Design/Materials and MethodsA cylindrical diffuser was developed to have a 5 mm active segment to emit laser light circumferentially. Twenty one New Zealand white rabbits were enrolled in this study. The cylindrical diffuser was inserted transorally under bronchoscopic view and the diffused light was delivered to tracheal mucosa 2 cm below the level of vocal cord. Input power of irradiation was 10 W, 5 seconds in group A (n = 7), 10 W, 7 seconds in group B (n = 7), and 8 W, 5 seconds in group C (n = 7). The degree of tracheal stenosis was observed weekly and the rabbits were euthanized 4 weeks after the laser irradiation.ResultsThe degree of stenosis in group B (90–98%) was significantly larger than that of group A (75–92%) (P = 0.004), while degree in group C (24–35%) was significantly smaller than that of group A (P < 0.001). Two rabbits of group A were euthanized at 3 weeks due to costal retraction. In group B, six rabbits died within 3 weeks after laser irradiation due to severe tracheal stenosis and tracheal malacia, while one rabbit was euthanized 16 days after the irradiation. All rabbits in group C survived up to 4 weeks. Survival between three groups showed significant difference (P = 0.001).ConclusionThe degree of stenosis was significantly different according to the delivered optical energy to tracheal mucosa. Therefore, the proposed model may be used in animal studies to emulate variable grades of tracheal stenosis. Lasers Surg. Med. 49:372–379, 2017. © 2016 Wiley Periodicals, Inc.