bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial variability in photosynthetic and heterotrophic activity drives localized δ13Corg fluctuations and carbonate precipitation in hypersaline microbial mats
Authors: Houghton J. , Fike D. , Druschel G. , Orphan V. , Hoehler T. M. , Des Marais D. J. 
Published: October 2014

AbstractModern laminated photosynthetic microbial mats are ideal environments to study how microbial activity creates and modifies carbon and sulfur isotopic signatures prior to lithification. Laminated microbial mats from a hypersaline lagoon (Guerrero Negro, Baja California, Mexico) maintained in a flume in a greenhouse at NASA Ames Research Center were sampled for δ13C of organic material and carbonate to assess the impact of carbon fixation (e.g., photosynthesis) and decomposition (e.g., bacterial respiration) on δ13C signatures. In the photic zone, the δ13Corg signature records a complex relationship between the activities of cyanobacteria under variable conditions of CO2 limitation with a significant contribution from green sulfur bacteria using the reductive TCA cycle for carbon fixation. Carbonate is present in some layers of the mat, associated with high concentrations of bacteriochlorophyll e (characteristic of green sulfur bacteria) and exhibits δ13C signatures similar to DIC in the overlying water column (−2.0‰), with small but variable decreases consistent with localized heterotrophic activity from sulfate‐reducing bacteria (SRB). Model results indicate respiration rates in the upper 12 mm of the mat alter in situ pH and concentrations to create both phototrophic CO2 limitation and carbonate supersaturation, leading to local precipitation of carbonate minerals. The measured activity of SRB with depth suggests they variably contribute to decomposition in the mat dependent on organic substrate concentrations. Millimeter‐scale variability in the δ13Corg signature beneath the photic zone in the mat is a result of shifting dominance between cyanobacteria and green sulfur bacteria with the aggregate signature overprinted by heterotrophic reworking by SRB and methanogens. These observations highlight the impact of sedimentary microbial processes on δ13Corg signatures; these processes need to be considered when attempting to relate observed isotopic signatures in ancient sedimentary strata to conditions in the overlying water column at the time of deposition and associated inferences about carbon cycling.
The Art of Writing Place
Authors: Ward Miranda 
Published: October 2014

AbstractThis paper provides an overview of recent work by academic geographers who use creative approaches to writing, both structurally and linguistically, to explore and advance themes relating to space and place. It places this work in the context of other contemporary engagements with creative practices in cultural geography and sets out some of the possibilities for, as well as the challenges associated with, a “creative‐critical” approach to writing geography. It outlines several ways in which this approach can help cultural geographers engage with certain ideas about place through a focus on three particular themes: (1) the idea of place as something fluid and always‐becoming; (2) the relationship between the body and place; and (3) the spatiality of text.
Age‐associated decrease of senescence marker protein‐30/gluconolactonase in individual mouse liver cells: Immunohistochemistry and immunofluorescence
Authors: Ishigami Akihito , Masutomi Hirofumi , Handa Setsuko , Maruyama Naoki 
Published: October 2014

AimSenescence marker protein‐30 (SMP30)/gluconolactonase (GNL) is an age‐associated protein in that its presence decreases with aging. Here, we used immunohistochemical analysis to investigate the changes of SMP30/GNL in individual cells of the liver from progressively aged mice.MethodsMale C57BL/6 strain mice at 1, 3, 6, 12, 24 and 30 months‐of‐age were the source of hepatic cells used to detect SMP30/GNL. Liver sections from these mice were subjected to immunohistochemical staining with anti‐SMP30/GNL antibody. For immunofluorescent staining, primary cultured hepatocytes from mice at various ages were stained with SMP30/GNL and albumin.ResultsIn liver cells from mice of all ages, SMP30/GNL staining appeared in some but not all parenchymal cells, and localized in both the nuclei and cytoplasm. Moreover, SMP30/GNL‐positive staining of parenchymal cells was present only around central vein areas, but not at sites of portal veins. Furthermore, the number of SMP30/GNL‐positive cells increased as mice aged from 1 to 12 months, then decreased from the 12th to 24th month. Results were similar in primary cultured hepatocytes from mice of various ages.ConclusionsSMP30/GNL‐positive cells localized mainly around the central veins in the livers of mice and decreased numerically with aging, although there was no age‐related change in counts of albumin‐positive cells. SMP30/GNL protein occupied the nuclei and cytoplasm. Therefore, nuclear SMP30/GNL protein might be a regulatory factor specific for genes whose expression governs transcription and the aging process. Geriatr Gerontol Int 2015; 15: 804–810.
Tumour‐infiltrating lymphocytes and expression of programmed death ligand 1 (PD‐L1) in melanoma brain metastases
Authors: Berghoff Anna Sophie , Ricken Gerda , Widhalm Georg , Rajky Orsolya , Dieckmann Karin , Birner Peter , Bartsch Rupert , Höller Christoph , Preusser Matthias 
Published: October 2014

AimsIn this study we aimed to characterize immune infiltrates and expression of programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) in a series of melanoma BM to provide a basis for experimental therapy using immune checkpoint inhibitors.Methods and resultsWe investigated expression of PD‐1, PD‐L1, CD3, CD8, CD45RO, forkhead box protein 3 (FoxP3), CD20 and BRAF V600E by immunohistochemistry in melanoma BM samples. Forty‐three specimens [27 of which (62.8%) were BRAF V600E‐positive] were available. CD3+ tumour‐infiltrating lymphocytes (TILs) were evident in 33 specimens (76.7%), CD8+ in 39 (90.7%), CD45RO+ in 32 (74.4%), PD‐1+ in 27 (62.8%), FoxP3+ in 21 (48.8%) and CD20+ TILs in 19 (44.2%). Tumour PD‐L1 expression was observed in 22 specimens (51.1%), and in nine of these (40.9%) expression was observed in more than 5% of tumour cells. PD‐L1 expression was associated with higher density of PD‐1+ (P < 0.001), CD3+ (P = 0.014) and FoxP3+ (P < 0.001) TIL infiltration. Density of CD3+ TILs was associated with density of CD8+ (P < 0.001), PD‐1+ (P < 0.001) and CD45RO+ (P < 0.001) TILs. PD‐L1 expression or PD‐1+, CD3+, CD8+ or CD45RO+ TILs density did not correlate with BRAF V600E status, previous systemic therapy or survival (P > 0.05).ConclusionsMelanoma BM showed considerable lymphocytic infiltrates and expression of PD‐L1 in the majority of investigated specimens, with high PD‐L1 expression found predominantly in regions of abundant inflammation. Our data indicate that clinical studies should investigate the value of checkpoint inhibitors in patients with melanoma BMs.
TNF‐α and LPS activate angiogenesis via VEGF and SIRT1 signalling in human dental pulp cells
Authors: Shin M. R. , Kang S. K. , Kim Y. S. , Lee S. Y. , Hong S. C. , Kim E.‐C. 
Published: October 2014

AbstractAimTo assess whether SIRT1 and VEGF are responsible for tumour necrosis factor‐α (TNF‐α) and lipopolysaccharide (LPS)‐induced angiogenesis and to examine the molecular mechanism(s) of action in human dental pulp cells (HDPCs).MethodologyImmortalized HDPCs obtained from Prof. Takashi Takata (Hiroshima University, Japan) were treated with LPS (1 μg mL−1) and TNF‐α (10 ng mL−1) for 24 h. mRNA and protein levels were examined by RT‐PCR and Western blotting, respectively. Migration and tube formation were examined in human umbilical vein endothelial cells (HUVECs). The data were analysed by one‐way anova. Statistical analysis was performed at α = 0.05.ResultsLPS and TNF‐α upregulated VEGF and SIRT1 mRNA and protein levels. Inhibition of SIRT1 activity by sirtinol and SIRT1 siRNA or inhibition of the VEGF receptor by CBO‐P11 significantly attenuated LPS + TNF‐α‐stimulated MMPs production in HDPCs, as well as migration and tube formation in HUVECs (P < 0.05). Furthermore, sirtinol, SIRT1 siRNA and CBO‐P11 attenuated phosphorylation of Akt, extracellular signal‐regulated kinase (ERK), p38 and c‐Jun N‐terminal kinase (JNK) and the nuclear translocation of NF–κB p65. Pre‐treatment with inhibitors of p38, ERK, JNK, PI3K and NF‐κB decreased LPS + TNF‐α‐induced VEGF and SIRT1 expression, MMPs activity in HDPCs and angiogenesis (P < 0.05) in HUVECs.ConclusionsTNF‐α and LPS led to upregulation of VEGF and SIRT1, and subsequent upregulation of MMP‐2 and MMP‐9 production, and promote angiogenesis via pathways involving PI3K, p38, ERK, JNK and NF‐κB. The results suggest that inhibition of SIRT1 and VEGF might attenuate pro‐inflammatory mediator‐induced pulpal disease.
Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxinA in the treatment of glabellar lines: A multicenter, randomized, double‐blind, active‐controlled study
Authors: Won Chong Hyun , Kim Hyun Kyu , Kim Beom Joon , Kang Hoon , Hong Joon Pio , Lee Su‐Young , Kim Chung‐Sei 
Published: October 2014

AbstractA novel botulinum neurotoxin type A (DWP450; Daewoong Pharmaceutical, Seoul, Korea) has recently been introduced for the treatment of facial wrinkles. The efficacy of this agent has previously been demonstrated in an in vivo study using an electrophysiological protocol in a rat model. To compare the efficacy and safety of DWP450 with onabotulinumtoxinA (OBoNT) for use in the treatment of glabellar lines, we performed a multicenter, double‐blind, randomized, active‐controlled trial comparing DWP450 and OBoNT (Allergan Inc., Irvine, CA, USA). A total of 268 subjects with moderate to severe glabellar lines were randomized at a 1 : 1 ratio. Each patient received treatment with 20 U of study medication. Maximum frown responder rates at week 4 were measured to analyze the primary efficacy endpoint. To evaluate secondary efficacy endpoints, response rates were measured at weeks 8, 12, and 16, at maximum frown and rest. Specifically, responder rates at both maximum frown and at rest were assessed based on clinical photography. Subject degree of satisfaction and self‐assessed rate of response were also measured. Adverse events (AEs) were documented to evaluate safety. Responder rate by physician‐rating severity at maximal contraction at week 4 was 93.89% in the DWP450 group and 88.64% in OBoNT group. As the lower limit of the 97.5% one‐sided confidence interval (– 1.53%) surpassed the – 15% threshold, we determined that DWP450 was not inferior to OBoNT. For the secondary efficacy endpoint analyses, no significant differences were observed between the two groups for any variable at any point in time. The incidences of AEs were similar for the two groups. Most of AEs were considered mild. DWP450 and OBoNT were comparable in efficacy and safety in the treatment of glabellar lines.
Circulating level of CD4+ CD25+ FOXP3+ T cells in patients with chronic urticaria
Authors: Arshi Saba , Babaie Delara , Nabavi Mohammad , Tebianian Majid , Ghalehbaghi Babak , Jalali Farhad , Ahmadvand Alireza , Gholami Reza 
Published: October 2014

AbstractBackgroundCD4+ CD25+ T‐regulatory (Treg) cells play critical roles in maintaining peripheral tolerance and preventing autoimmunity. As characteristics of Treg cells have not been precisely investigated in chronic urticaria (CU) yet, this study was performed.ObjectiveTo determine the frequencies of circulating CD4+ CD25+ FOXP3+ T cells and serum levels of interleukin (IL)‐10, transforming growth factor (TGF)‐β, and IL‐17 in patients with chronic autoimmune urticaria and chronic idiopathic urticaria compared to healthy controls.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with CU and healthy controls. The frequency of CD4+ CD25+ T cells in PBMCs and expression levels of FOXP3 were detected by flow cytometry. The serum levels of IL‐10, TGF‐β, and IL‐17 were measured by enzyme‐linked immunosorbent assay.ResultsA significant decrease in the percentage of circulating CD4+ CD25+ FOXP3+ T cells was detected in patients with CU, compared to control subjects. However, no significant difference was detected on the serum levels of IL‐10, TGF‐β, and IL‐17 between patients with CU and control subjects.ConclusionsThis study demonstrated that the frequency of Treg cells in PBMCs was decreased in patients with CU. Further studies are needed to clarify the exact role of Treg cells in the pathogenesis of CU and factors regulating their function.
A bioactive molecule in a complex wound healing process: platelet‐derived growth factor
Authors: Kaltalioglu Kaan , Coskun‐Cevher Sule 
Published: October 2014

AbstractWound healing is considered to be particularly important after surgical procedures, and the most important wounds related to surgical procedures are incisional, excisional, and punch wounds. Research is ongoing to identify methods to heal non‐closed wounds or to accelerate wound healing; however, wound healing is a complex process that includes many biological and physiological events, and it is affected by various local and systemic factors, including diabetes mellitus, infection, ischemia, and aging. Different cell types (such as platelets, macrophages, and neutrophils) release growth factors during the healing process, and platelet‐derived growth factor is a particularly important mediator in most stages of wound healing. This review explores the relationship between platelet‐derived growth factor and wound healing.
Multifunctional cytomegalovirus (CMV)‐specific CD8+ T cells are not restricted by telomere‐related senescence in young or old adults
Authors: Riddell Natalie E. , Griffiths Stephen J. , Rivino Laura , King David C. B. , Teo Guo H. , Henson Sian M. , Cantisan Sara , Solana Rafael , Kemeny David M. , MacAry Paul A. , Larbi Anis , Akbar Arne N. 
Published: October 2014

SummaryAntigen‐specific multifunctional T cells that secrete interferon‐γ, interleukin‐2 and tumour necrosis factor‐α simultaneously after activation are important for the control of many infections. It is unclear if these CD8+ T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi‐parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen‐specific CD8+ T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow‐FISH). The end‐stage/senescent CD8+ CD45RA+ CD27− T‐cell subset increases significantly during ageing and this is exaggerated in CMV immune‐responsive subjects. However, these end‐stage cells do not have the shortest telomeres, implicating additional non‐telomere‐related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)‐specific CD8+ T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti‐CD3 or NLV peptide, similar proportions of triple‐cytokine‐producing cells are found in CD8+ T cells at all stages of differentiation in both age groups. Furthermore, these multi‐functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)‐specific CD8+ T cells that secrete interferon‐γ, interleukin‐2 and tumour necrosis factor‐α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion.
Microscopic and Spectroscopic Characterization of Stacking‐Sequence Disordered SiC
Authors: Ohyanagi Manshi , Imai Takahito , Toyofuku Naoki , Nakagawa Daisuke , Munir Zuhair A. 
Published: October 2014

Nanometric silicon carbide (SiC) powder (~5 nm) with a stacking‐sequence disordered structure (SD‐SiC), synthesized from elemental powders of Si and C, was investigated by microscopic and several spectroscopic methods. The structure of SD‐SiC was characterized by transmission electron microscopy (TEM), 13C, and 29Si‐NMR, and by infrared (IR), Raman, and X‐ray photoelectron spectroscopy (XPS) methods. TEM characterizations showed relatively large deviations of the lattice parameters in the as‐synthesized SiC, indicative of the presence of stacking‐sequence disorder. IR analysis showed a weaker Si‐C bond in the SD‐SiC than in the 3C‐SiC. XPS determinations showed that C and Si in SD‐SiC are similar to those in 3C‐SiC. Broader peaks of 29Si and 13C MAS‐NMR also indicate that the structure of SD‐SiC is different from that of 3C‐SiC. Raman spectroscopy exhibited activities for the crystalline polytypes and the amorphous of SiC but lack of them for the SD‐SiC. The inactivity of Raman spectroscopy for the SD‐SiC along with large deviation of the lattice constant and the extremely broad X‐ray diffraction peaks would indicate that SD‐SiC is a possible intermediate state between conventional polytype SiC and amorphous SiC, that is, a possible new type of SiC.
In Situ Thermally Induced Attenuation in Sapphire Optical Fibers Heated to 1400°C
Authors: Petrie Christian M. , Blue Thomas E. 
Published: October 2014

The purpose of this work was to determine the spectral loss of sapphire optical fibers as a function of temperature to determine the suitability of using sapphire optical fiber‐based instrumentation in extremely high‐temperature applications such as coal gasifers, or potentially in advanced high‐temperature nuclear reactors. In this work, the broadband (450–2200 nm) optical attenuation of two commercially available sapphire optical fibers was monitored in situ as the fibers were heated in steps to temperatures up to 1400°C. The results presented in this work are the first known reporting of the broadband spectral loss in sapphire fibers (as opposed to bulk sapphire) as a function of temperature. The added attenuation in the sapphire fibers seemed to reach a steady‐state at temperatures of 1300°C and below, and remained below 3.7 dB/m at all measurable wavelengths. At 1400°C, rapid increases in attenuation were observed that appeared to increase as the square root of heating time, indicating a diffusion‐limited process. Cooling to room temperature in steps resulted in recovery of a large portion of the thermally induced attenuation, suggesting that the effects caused by heating at 1400°C introduced additional attenuation that was very temperature dependent. Based on comparison with previous work and on the spectral features of the added attenuation observed in this work, heating at 1400°C could have caused high‐temperature oxidation of the sapphire fibers, which resulted in a temperature‐dependent scattering loss mechanism.
Satellite glial cells in dorsal root ganglia are activated in streptozotocin‐treated rodents
Authors: Hanani Menachem , Blum Erez , Liu Shuangmei , Peng Lichao , Liang Shangdong 
Published: October 2014

AbstractNeuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ‐treatment the number of neurons surrounded with GFAP‐positive SGCs in dorsal root ganglia increased 4‐fold in mice and 5‐fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2‐fold in STZ‐treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target.
Differential uPAR recruitment in caveolar‐lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis
Authors: Margheri Francesca , Papucci Laura , Schiavone Nicola , D'Agostino Riccardo , Trigari Silvana , Serratì Simona , Laurenzana Anna , Biagioni Alessio , Luciani Cristina , Chillà Anastasia , Andreucci Elena , Del Rosso Tommaso , Margheri Giancarlo , Del Rosso Mario , Fibbi Gabriella 
Published: October 2014

AbstractGangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid‐rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar‐lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro‐angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid‐supported mobile bilayer lipid membranes with raft‐like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR‐GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1‐enriched biomimetic membranes, were validated by identifying a pro‐angiogenic activity of GM1‐enriched EPCs, based on GM1‐dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti‐angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar‐raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar‐raft partitioning of uPAR, as opposed to control and GM3‐challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis.