bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3‐L1 adipocytes via PPARγ signaling pathway
Authors: Shyni Gangadharan Leela , Kavitha Sasidharan , Indu Sasidharan , Arya Anil Das , Anusree Sasidharan Suseela , Vineetha Vadavanath Prabhakaran , Vandana Sankar , Sundaresan Andikannu , Raghu Kozhiparambil Gopalan 
Published: December 2014

SummaryThe thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator‐activated receptor gamma (PPARγ). Naturally occurring PPARγ modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPARγ activity. In the present work, we studied chebulagic acid (CHA) isolated from fruits of Terminalia chebula with respect to its effect on adipogenesis, glucose transport, and endocrine function of adipocyte. The mRNA expression profile of PPARγ target gene CCAAT/enhancer‐binding protein alpha (C/EBP‐α) was analyzed by qRT‐PCR. The putative binding mode and the potential ligand‐target interactions of CHA, with PPARγ was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARγ signaling and adipogenesis dose dependently but in a moderate way, less than rosiglitazone. GLUT4 expression and adiponectin secretion was increased by CHA treatment. The mRNA expression of PPARγ target gene C/EBP‐α was increased in CHA‐treated adipocytes. The comparison of results of various parameters of adipogenesis, insulin sensitivity, endocrine function and molecular docking experiments of roziglitazone and chebulagic acid indicate that the latter behaves like partial PPARγ agonist which could be exploited for phytoceutical development against T2DM. © 2014 BioFactors, 40(6):646–657, 2014
Endoplasmic reticulum proteins quality control and the unfolded protein response: The regulative mechanism of organisms against stress injuries
Authors: Fu Xi Ling , Gao Dong Sheng 
Published: December 2014

AbstractThe endoplasmic reticulum is the cellular compartment in which secretory proteins are synthesized and folded. Perturbations of endoplasmic reticulum homeostasis lead to the accumulation of unfolded proteins. The activation of the unfolded protein response during endoplasmic reticulum stress transmits information about the status of protein folding to the cytosol and nucleus. The unfolded protein response leads to the upregulation of genes encoding endoplasmic reticulum chaperones, attenuation of translation, and initiation of the endoplasmic reticulum quality control system to restore endoplasmic reticulum homeostasis. When the unfolded protein response is insufficient to rebuild the steady state in endoplasmic reticulum, the programmed cell death or apoptosis would be initiated, by triggering cell injuries, even to cell death through apoptosis signals. In this review, we briefly outline research on the chaperones and foldases conserved in eukaryotes and plants, and describe the general principles and mechanisms of the endoplasmic reticulum quality control and the unfolded protein response. We describe the current models for the molecular mechanism of the unfolded protein response in plants, and emphasize the role of inositol requiring enzyme‐1‐dependent network in the unfolded protein response. Finally, we give a general overview of the directions for future research on the unfolded protein response in plants and its role in the response to environmental stresses. © 2014 BioFactors, 40(6):569–585, 2014
Automated analysis of flow cytometric data for measuring neutrophil CD64 expression using a multi‐instrument compatible probability state model
Authors: Wong Linda , Hill Beth L. , Hunsberger Benjamin C. , Bagwell C. Bruce , Curtis Adam D. , Davis Bruce H. 
Published: December 2014

BackgroundLeuko64TM (Trillium Diagnostics) is a flow cytometric assay that measures neutrophil CD64 expression and serves as an in vitro indicator of infection/sepsis or the presence of a systemic acute inflammatory response. Leuko64 assay currently utilizes QuantiCALC, a semiautomated software that employs cluster algorithms to define cell populations. The software reduces subjective gating decisions, resulting in interanalyst variability of <5%. We evaluated a completely automated approach to measuring neutrophil CD64 expression using GemStoneTM (Verity Software House) and probability state modeling (PSM).MethodsFour hundred and fifty‐seven human blood samples were processed using the Leuko64 assay. Samples were analyzed on four different flow cytometer models: BD FACSCanto II, BD FACScan, BC Gallios/Navios, and BC FC500. A probability state model was designed to identify calibration beads and three leukocyte subpopulations based on differences in intensity levels of several parameters. PSM automatically calculates CD64 index values for each cell population using equations programmed into the model. GemStone software uses PSM that requires no operator intervention, thus totally automating data analysis and internal quality control flagging. Expert analysis with the predicate method (QuantiCALC) was performed. Interanalyst precision was evaluated for both methods of data analysis.ResultsPSM with GemStone correlates well with the expert manual analysis, r2 = 0.99675 for the neutrophil CD64 index values with no intermethod bias detected. The average interanalyst imprecision for the QuantiCALC method was 1.06% (range 0.00–7.94%), which was reduced to 0.00% with the GemStone PSM. The operator‐to‐operator agreement in GemStone was a perfect correlation, r2 = 1.000.ConclusionAutomated quantification of CD64 index values produced results that strongly correlate with expert analysis using a standard gate‐based data analysis method. PSM successfully evaluated flow cytometric data generated by multiple instruments across multiple lots of the Leuko64 kit in all 457 cases. The probability‐based method provides greater objectivity, higher data analysis speed, and allows for greater precision for in vitro diagnostic flow cytometric assays. © 2015 International Clinical Cytometry Society
The beneficial effect of growth hormone treatment on islet mass in streptozotocin‐treated mice
Authors: Scheinman Eyal J. , Damouni Rawan , Caspi Avishay , Shen‐Orr Zila , Tiosano Dov , LeRoith Derek 
Published: December 2014

AbstractBackgroundType 1 diabetes is an autoimmune disease, characterized by a loss of pancreatic β‐cell mass and function, which results in dramatic reductions in insulin secretion and circulating insulin levels. Patients with type 1 diabetes are traditionally treated with insulin injections and insulin pumps ex vivo or undergo transplantation. Growth hormone (GH) has been shown to be involved in β‐cell function and survival in culture.MethodsTwelve‐week‐old female C57BL/6 mice were treated with streptozotocin and monitored for their weight and blood glucose levels. Fourteen days post‐initial injection, these mice were separated into two groups at random. One group was treated with GH while the other treated with vehicle for up to 3 weeks. These mice were compared with mice not treated with streptozotocin.ResultsUnder our experimental conditions, we observed that mice treated with GH had larger islets and higher serum insulin levels than streptozotocin‐treated mice treated with saline (0.288 vs. 0.073 ng/mL, p < 0.01).ConclusionsOur data demonstrate that GH may rescue islets and therefore may possess therapeutic potential in the treatment of type 1 diabetes, although consideration should be made regarding GH's effect on insulin resistance. Copyright © 2014 John Wiley & Sons, Ltd.
Modulation of p53 and met expression by Krüppel‐like factor 8 regulates zebrafish cerebellar development
Authors: Tsai Ming‐Yuan , Lu Yu‐Fen , Liu Yu‐Hsiu , Lien Huang‐Wei , Huang Chang‐Jen , Wu Jen‐Leih , Hwang Sheng‐Ping L. 
Published: December 2014

ABSTRACTKrüppel‐like factor 8 (Klf8) is a zinc‐finger transcription factor implicated in cell proliferation, and cancer cell survival and invasion; however, little is known about its role in normal embryonic development. Here, we show that Klf8 is required for normal cerebellar development in zebrafish embryos. Morpholino knockdown of klf8 resulted in abnormal cerebellar primordium morphology and the induction of p53 in the brain region at 24 hours post‐fertilization (hpf). Both p53‐dependent reduction of cell proliferation and augmentation of apoptosis were observed in the cerebellar anlage of 24 hpf‐klf8 morphants. In klf8 morphants, expression of ptf1a in the ventricular zone was decreased from 48 to 72 hpf; on the other hand, expression of atohla in the upper rhombic lip was unaffected. Consistent with this finding, Purkinje cell development was perturbed and granule cell number was reduced in 72 hpf‐klf8 morphants; co‐injection of p53 MOsp or klf8 mRNA substantially rescued development of cerebellar Purkinje cells in klf8 morphants. Hepatocyte growth factor/Met signaling is known to regulate cerebellar development in zebrafish and mouse. We observed decreased met expression in the tectum and rhombomere 1 of 24 hpf‐klf8 morphants, which was largely rescued by co‐injection with klf8 mRNA. Moreover, co‐injection of met mRNA substantially rescued formation of Purkinje cells in klf8 morphants at 72 hpf. Together, these results demonstrate that Klf8 modulates expression of p53 and met to maintain ptf1a‐expressing neuronal progenitors, which are required for the appropriate development of cerebellar Purkinje and granule cells in zebrafish embryos. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 908–926, 2015
Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions
Authors: Barleben Maria , Stoppel Christian M. , Kaufmann Jörn , Merkel Christian , Wecke Thoralf , Goertler Michael , Heinze Hans‐Jochen , Hopf Jens‐Max , Schoenfeld Mircea A. 
Published: December 2014

AbstractPatients with striate cortex lesions experience visual perception loss in the contralateral visual field. In few patients, however, stimuli within the blind field can lead to unconscious (blindsight) or even conscious perception when the stimuli are moving (Riddoch syndrome). Using functional magnetic resonance imaging (fMRI), we investigated the neural responses elicited by motion stimulation in the sighted and blind visual fields of eight patients with lesions of the striate cortex. Importantly, repeated testing ensured that none of the patients exhibited blindsight or a Riddoch syndrome. Three patients had additional lesions in the ipsilesional pulvinar. For blind visual field stimulation, great care was given that the moving stimulus was precisely presented within the borders of the scotoma. In six of eight patients, the stimulation within the scotoma elicited hemodynamic activity in area human middle temporal (hMT) while no activity was observed within the ipsilateral lesioned area of the striate cortex. One of the two patients in whom no ipsilesional activity was observed had an extensive lesion including massive subcortical damage. The other patient had an additional focal lesion within the lateral inferior pulvinar. Fiber‐tracking based on anatomical and functional markers (hMT and Pulvinar) on individual diffusion tensor imaging (DTI) data from each patient revealed the structural integrity of subcortical pathways in all but the patient with the extensive subcortical lesion. These results provide clear evidence for the robustness of direct subcortical pathways from the pulvinar to area hMT in patients with striate cortex lesions and demonstrate that ipsilesional activity in area hMT is completely independent of conscious perception. Hum Brain Mapp 36:1585–1594, 2015. © 2014 Wiley Periodicals, Inc.
Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer's disease and neuronal loss
Authors: Ager Rahasson R. , Davis Joy L. , Agazaryan Andy , Benavente Francisca , Poon Wayne W. , LaFerla Frank M. , Blurton‐Jones Mathew 
Published: December 2014

ABSTRACTAlzheimer's disease (AD) is the most prevalent age‐related neurodegenerative disorder, affecting over 35 million people worldwide. Pathologically, AD is characterized by the progressive accumulation of β‐amyloid (Aβ) plaques and neurofibrillary tangles within the brain. Together, these pathologies lead to marked neuronal and synaptic loss and corresponding impairments in cognition. Current treatments, and recent clinical trials, have failed to modify the clinical course of AD; thus, the development of novel and innovative therapies is urgently needed. Over the last decade, the potential use of stem cells to treat cognitive impairment has received growing attention. Specifically, neural stem cell transplantation as a treatment for AD offers a novel approach with tremendous therapeutic potential. We previously reported that intrahippocampal transplantation of murine neural stem cells (mNSCs) can enhance synaptogenesis and improve cognition in 3xTg‐AD mice and the CaM/Tet‐DTA model of hippocampal neuronal loss. These promising findings prompted us to examine a human neural stem cell population, HuCNS‐SC, which has already been clinically tested for other neurodegenerative disorders. In this study, we provide the first evidence that transplantation of research grade HuCNS‐SCs can improve cognition in two complementary models of neurodegeneration. We also demonstrate that HuCNS‐SC cells can migrate and differentiate into immature neurons and glia and significantly increase synaptic and growth‐associated markers in both 3xTg‐AD and CaM/Tet‐DTA mice. Interestingly, improvements in aged 3xTg‐AD mice were not associated with altered Aβ or tau pathology. Rather, our findings suggest that human NSC transplantation improves cognition by enhancing endogenous synaptogenesis. Taken together, our data provide the first preclinical evidence that human NSC transplantation could be a safe and effective therapeutic approach for treating AD. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Determination of the type and quantity of sialic acid in the egg jelly coat of the sea urchin Paracentrotus lividus using capillary LC‐ESI‐MS/MS
Authors: Yeşilyurt Batuhan , Şahar Umut , Deveci Remziye 
Published: December 2014

SUMMARYSialic acid is a terminal sugar of carbohydrate chains that participates in numerous biological events. Recent studies have explored the mechanism of carbohydrate‐mediated fertilisation to understand the biochemistry of fertilisation, although the type and quantity of sialic acid and the role of sialic acid during fertilisation remain unknown. Echinoderm fertilisation in particular has been studied extensively, yet our understanding of the mechanisms of carbohydrate‐mediated fertilisation and the role of sialic acid remains incomplete. In this study, we characterised the sialic acid types in the egg jelly coat of the sea urchin, Paracentrotus lividus, using the sensitive analytical system capillary liquid chromatography electro‐spray ionisation tandem mass spectrometry (capLC‐ESI‐MS/MS). First, we isolated the egg jelly coat and released its sialic acid using acid treatment. These sialic acids were derivatised with 1,2‐diamino‐4,5‐methylenediaoxy‐benzene dihydrochloride (DMB) and injected into the capLC‐ESI‐MS/MS system. When compared with standards, we identified twelve different types of sialic acid according to their retention times and collision‐induced dissociation fragments. The mass spectral data revealed that Neu5Gc, Neu5Ac, Neu5GcS, and Neu5Gc9Ac were the predominant types of sialic acid in the sea urchin jelly coat, with Neu5Gc being the most abundant. Other types of sialic acid detected included Neu5AcS, Neu5Gc7,9Ac2, Neu5,9Ac2, Neu5Gc8Ac, Neu5Gc7Ac, Neu5,7Ac2, Neu5Gc8,9Ac2, and Neu5,8Ac2. The types and quantities of sialic acid that we detected in the egg jelly coat will aid in the discovery of new sialic acid‐specific receptors on the sperm membrane. Mol. Reprod. Dev. 82: 115–122, 2015. © 2014 Wiley Periodicals, Inc.
Cross‐sectional mapping of hole concentrations as a function of copper treatment in CdTe photo‐voltaic devices
Authors: Korevaar Bas A. , Zorn Gilad , Raghavan Kamala C. , Cournoyer James R. , Dovidenko Katharine 
Published: December 2014

AbstractThe carrier density and carrier density distribution within CdTe solar cells were studied with scanning capacitance microscopy (SCM). The CdTe solar cells were studied after every process step and as a function of varying copper treatment conditions. It was found that the CdTe film is practically undoped after deposition and after CdCl2 treatment, while after the copper step the carrier density distribution is non‐uniform with a mixture of p‐type and intrinsic grains in the CdTe film. These SCM observations were also confirmed with device performance data as well as capacitance–voltage measurements and Van der Pauw Hall measurements. Copyright © 2014 John Wiley & Sons, Ltd.
Rapid screening of residual pesticides on fruits and vegetables using thermal desorption electrospray ionization mass spectrometry
Authors: Shiea Christopher , Huang Yeou‐Lih , Liu De‐Lin , Chou Chih‐Chang , Chou Jo‐Han , Chen Peng‐Yu , Shiea Jentaie , Huang Min‐Zong 
Published: December 2014

RATIONALEConventional mass spectrometry is encumbered by laborious and inconvenient sample pretreatment. Ambient thermal desorption electrospray ionization mass spectrometry (TD‐ESI‐MS) is most noted for its rapid, simple, and sensitive detection capabilities. In this study, TD‐ESI‐MS was used to rapidly characterize residual pesticides on the surfaces of fruits and vegetables.METHODSA direct sampling probe was used to obtain analytes from sample surfaces. MS and MS/MS analyses were performed on fruits and vegetables via TD‐ESI‐MS. External calibration curves and reproducibility tests were performed using liquid pesticide standards. Pesticide decay and distribution on samples was studied, as well as the removal of residual pesticides via soaking in water or detergent baths.RESULTSSince sample pretreatment was unnecessary, an analysis was completed in approximately 15 s or less, with no visible sample damage. Mass spectra were obtained for 22 pesticides. Linear calibrations (R2 from 0.9414–0.999) had limits of detection as low as 0.5 µg·L–1, with satisfactory reproducibilities for liquids and solids. Pesticides on sample surfaces decayed over 2 weeks under ambient conditions. Residual pesticides localized at the fruit peel. Detergent baths removed more pesticide than water baths.CONCLUSIONSTD‐ESI‐MS was used to rapidly screen residual pesticides in liquids and solids. Pesticides were found on fruits and vegetables, where the decay, distribution, and removal of pesticides on samples were also explored. Due to short analysis times, the technique allows for high‐throughput analyses for applications in food and environmental safety. Copyright © 2014 John Wiley & Sons, Ltd.
Identification of plasma protease derived metabolites of glucagon and their formation under typical laboratory sample handling conditions
Authors: Howard James W. , Kay Richard G. , Tan Tricia , Minnion James , Creaser Colin S. 
Published: December 2014

RATIONALEGlucagon modulates glucose production, and it is also a biomarker for several pathologies. It is known to be unstable in human plasma, and consequently stabilisers are often added to samples, although these are not particularly effective. Despite this, there have not been any studies to identify in vitro plasma protease derived metabolites; such a study is described here. Knowledge of metabolism should allow the development of more effective sample stabilisation strategies.METHODSSeveral novel metabolites resulting from the incubation of glucagon in human plasma were identified using high‐resolution mass spectrometry with positive electrospray ionisation. Tandem mass spectrometric (MS/MS) scans were acquired for additional confirmation using a QTRAP. Separation was performed using reversed‐phase ultra‐high‐performance liquid chromatography. The formation of these metabolites was investigated during a time‐course experiment and under specific stress conditions representative of typical laboratory handling conditions. Clinical samples were also screened for metabolites.RESULTSGlucagon3‐29 and [pGlu]3glucagon3‐29 were the major metabolites detected, both of which were also present in clinical samples. We also identified two oxidised forms of [pGlu]3glucagon3‐29 as well as glucagon19‐29, or 'miniglucagon', along with the novel metabolites glucagon20‐29 and glucagon21‐29. The relative levels of these metabolites varied throughout the time‐course experiment, and under the application of the different sample handling conditions. Aprotinin stabilisation of samples had negligible effect on metabolite formation.CONCLUSIONSNovel plasma protease metabolites of glucagon have been confirmed, and their formation characterised over a time‐course experiment and under typical laboratory handling conditions. These metabolites could be monitored to assess the effectiveness of new sample stabilisation strategies, and further investigations into their formation could suggest specific enzyme inhibitors to use to increase sample stability. In addition the potential of the metabolites to affect immunochemistry‐based assays as a result of cross‐reactivity could be investigated. Copyright © 2014 John Wiley & Sons, Ltd.
A Test of the Serial Discontinuity Concept: Longitudinal Trends of Benthic Invertebrates in Regulated and Natural Rivers of Northern Canada
Authors: Ellis L. E. , Jones N. E. 
Published: December 2014

AbstractAbiotic and biotic impacts below impoundments within the context of the River Continuum (RCC) and the Serial Discontinuity Concepts (SDC) have been the focus of many lotic studies. Recovery gradients, however, are rarely examined in sufficient detail below dams. Further refinement and understanding are needed to inform science and river managers about regulated river ecology. In this study, we examine longitudinal patterns in abiotic and biotic characteristics in two regulated rivers in Northern Canada. We also examine spatial patterns on two natural rivers: a lake outlet river and a river with no lakes. Direct gradient analysis revealed that increases in periphyton, planktonic drift, primary production, substrate size, and changes in thermal regime at sites closest to the dam drive benthic invertebrate community characteristics. We test the Serial Discontinuity Concept by comparing predicted functional forms of each environmental variable with the empirically derived forms. Substrate size, periphyton biomass, and drift density increased below dams and recovered quickly within 5 km downstream, following closely with SDC predictions. The response of organic matter and water quality was variable, and benthic invertebrate richness recovered relatively quickly, contrary to SDC predictions. Thermal regime and flow took much longer to recover than most variables and represent a second longer gradient type below dams. Plecoptera, Gomphidae, and Simuliidae were strongly influenced by altered resource and habitat and may be good candidates for indicators and predictive modelling. Our results generally support predictions from the Serial Discontinuity Concept and highlight the need for the further testing and refinement of this concept. Copyright © 2014 John Wiley & Sons, Ltd.