bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dorsal hippocampus infusions of CNQX into the dentate gyrus disrupt expression of trace fear conditioning
Authors: Pierson Jamie L. , Pullins Shane E. , Quinn Jennifer J. 
Published: January 2015

ABSTRACTThe hippocampus is essential for the consolidation of some explicit long‐term memories, including trace conditioning. Lesions and pharmacological manipulations of the dorsal hippocampus (DH) have provided strong evidence for its involvement in the acquisition and expression of trace fear memories. However, no studies have specifically targeted DH subregions [CA1 and dentate gyrus (DG)] to determine their involvement in trace fear conditioning. In the present study, rats received bilateral cannulation targeting either the DG or CA1 of the DH. Following surgery, animals were trace fear conditioned. Forty‐eight hours following training, rats received bilateral infusions of the AMPA/kainate glutamate receptor antagonist, CNQX, or vehicle. Following the infusion, rats were placed in a novel context for the tone test. Rats that received CNQX into the DG froze significantly less during the tone and trace interval as compared to controls. Rats that received CNQX into the DH CA1 showed no difference in freezing during the tone or trace interval as compared to controls. These data support a role for the DG in the expression of trace tone fear conditioning. © 2015 Wiley Periodicals, Inc.
Enhanced QSAR models for drug‐triggered inhibition of the main cardiac ion currents
Authors: Wiśniowska Barbara , Mendyk Aleksander , Szlęk Jakub , Kołaczkowski Michał , Polak Sebastian 
Published: January 2015

ABSTRACTThe currently changing cardiac safety testing paradigm suggests, among other things, a shift towards using in silico models of cellular electrophysiology and assessment of a concomitant block of multiple ion channels. In this study, a set of four enhanced QSAR models have been developed: for the rapid delayed rectifying potassium current (IKr), slow delayed rectifying potassium current (IKs), peak sodium current (INa) and late calcium current (ICaL), predicting ion currents changes for the specific in vitro experiment from the 2D structure of the compounds. The models are a combination of both in vitro study parameters and physico‐chemical descriptors, which is a novel approach in drug–ion channels interactions modeling. Their predictive power assessed in the enhanced, more demanding than standard procedure, 10‐fold cross validation was reasonably high. Rough comparison with published pure in silico hERG interaction models shows that the quality of the model predictions does not differ from other models available in the public domain, however, it takes its advantage in accounting for inter‐experimental settings variability. Developed models are implemented in the Cardiac Safety Simulator, a commercially available platform enabling the in vitro–in vivo extrapolation of the drugs proarrhythmic effect and ECG simulation. A more comprehensive assessment of the effects of the compounds on ion channels allows for making more informed decisions regarding the risk – and thus avoidance – of exclusion of potentially safe and effective drugs. Copyright © 2015 John Wiley & Sons, Ltd.
The Association Between BMI and QCT-Derived Proximal Hip Structure and Strength in Older Men: A Cross-Sectional Study
Authors: Shen Jian , Nielson Carrie M , Marshall Lynn M , Lee David C , Keaveny Tony M , Orwoll Eric S ,   for the Osteoporotic Fractures in Men MrOS Research Group
Published: January 2015

ABSTRACT

Although higher body mass index (BMI) is associated with higher bone mineral density, recent evidence indicates that increased BMI may not be consistently associated with reduced hip fracture risk. Moreover, substantial proportions of hip fractures occur among overweight and obese men and women. The role of increased BMI and obesity on bone density, structure, and strength at the hip is not well understood. We conducted cross-sectional analyses between BMI and various density and structure measures derived from quantitative computed tomography (QCT)-scans of the proximal femur, in 3067 men (mean age: 73 y) from the Osteoporotic Fractures in Men Study (MrOS). Finite element (FE) analysis of hip QCT scans was performed for a subcohort of 672 men to provide a measure of femoral strength for a simulated sideways fall. The impact force was estimated using patient-specific weight and height information. Multivariable general linear models were used to examine the associations between BMI and hip QCT measures. The relationship of BMI with hip QCT measures was significantly different between men categorized as non-obese and obese (P for interaction ≤ 0.014). For non-obese men (BMI &lt; 30), increasing BMI was associated with higher integral, cortical and trabecular vBMD, integral volume, cross-sectional area, and percent cortical volume (all p &lt; 0.001). For obese men (BMI ≥30), increasing BMI was not associated with any of those parameters. In addition, compared to non-obese men, obese men had a higher hip strength, but also a higher ratio of impact force to strength (P  &lt; 0.0001), in theory increasing their risk of hip fracture despite their increased strength. These results provide a better understanding of hip fracture risk in obese men. © 2015 American Society for Bone and Mineral Research
Caveolin‐1 Mediates Inflammatory Breast Cancer Cell Invasion via the Akt1 Pathway and RhoC GTPase
Authors: Joglekar Madhura , Elbazanti Weam O. , Weitzman Matthew D. , Lehman Heather L. , van Golen Kenneth L. 
Published: January 2015

ABSTRACTWith a propensity to invade the dermal lymphatic vessels of the skin overlying the breast and readily metastasize, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. We previously reported that caveolin‐1 is overexpressed in IBC and that RhoC GTPase is a metastatic switch responsible for the invasive phenotype. RhoC‐driven invasion requires phosphorylation by Akt1. Using a reliable IBC cell line we set out to determine if caveolin‐1 expression affects RhoC‐mediated IBC invasion. Caveolin‐1 was down regulated by introduction of siRNA or a caveolin scaffolding domain. The ability of the cells to invade was tested and the status of Akt1 and RhoC GTPase examined. IBC cell invasion is significantly decreased when caveolin‐1 is down regulated. Activation of Akt1 is decreased when caveolin‐1 is down regulated, leading to decreased phosphorylation of RhoC GTPase. Thus, we report here that caveolin‐1 overexpression mediates IBC cell invasion through activation Akt1, which phosphorylates RhoC GTPase. J. Cell. Biochem. 116: 923–933, 2015. © 2015 Wiley Periodicals, Inc.
AHNAK2 Participates in the Stress‐Induced Nonclassical FGF1 Secretion Pathway
Authors: Kirov Aleksandr , Kacer Doreen , Conley Barbara A. , Vary Calvin P.H. , Prudovsky Igor 
Published: January 2015

ABSTRACTFGF1 is a nonclassically released growth factor that regulates carcinogenesis, angiogenesis, and inflammation. In vitro and in vivo, FGF1 export is stimulated by cell stress. Upon stress, FGF1 is transported to the plasma membrane where it localizes prior to transmembrane translocation. To determine which proteins participate in the submembrane localization of FGF1 and its export, we used immunoprecipitation mass spectrometry to identify novel proteins that associate with FGF1 during heat shock. The heat shock‐dependent association of FGF1 with the large protein AHNAK2 was observed. Heat shock induced the translocation of FGF1 and AHNAK2 to the cytoskeletal fraction. In heat‐shocked cells, FGF1 and the C‐terminal fragment of AHNAK2 colocalized with F‐actin in the vicinity of the cell membrane. Depletion of AHNAK2 resulted in a drastic decrease of stress‐induced FGF1 export but did not affect spontaneous FGF2 export and FGF1 release induced by the inhibition of Notch signaling. Thus, AHNAK2 is an important element of the FGF1 nonclassical export pathway. J. Cell. Biochem. 116: 1522–1531, 2015. © 2015 Wiley Periodicals, Inc.
Protonation Behavior of Histidine during HSF1 Activation by Physiological Acidification
Authors: Lu Ming , Park Jang‐Su 
Published: January 2015

ABSTRACTThe expression of eukaryotic molecular chaperones (heat shock proteins, HSPs) is triggered in response to a wide range of environmental stresses, including: heat shock, hydrogen peroxide, heavy metal, low‐pH, or virus infection. Biochemical and genetic studies have clearly shown the fundamental roles of heat shock factor 1 (HSF1) in stress‐inducible HSP gene expression, resistance to stress‐induced cell death, carcinogenesis, and other biological phenomena. Previous studies show that acidic pH changes within the physiological range directly activate the HSF1 function in vitro. However, the detailed mechanism is unclear. Though computational pKa‐predications of the amino acid side‐chain, acidic‐pH induced protonation of a histidine residue was found to be most‐likely involved in this process. The histidine 83 (His83) residue, which could be protonated by mild decrease in pH, causes mild acidic‐induced HSF1 activation (including in‐vitro trimerization, DNA binding, in‐vivo nuclear accumulation, and HSPs expression). His83, which is located in the loop region of the HSF1 DNA binding domain, was suggested to enhance the intermolecular force with Arginine 79, which helps HSF1 form a DNA‐binding competent. Therefore, low‐pH‐induced activation of HSF1 by the protonation of histidine can help us better to understand the HSF1 mechanism and develop more therapeutic applications (particularly in cancer therapy). J. Cell. Biochem. 116: 977–984, 2015. © 2015 Wiley Periodicals, Inc.
HIF‐2 Inhibition Supresses Inflammatory Responses and Osteoclastic Differentiation in Human Periodontal Ligament Cells
Authors: Bae Won‐Jung , Shin Mee‐Ran , Kang Soo‐Kyung , Zhang‐Jun  , Kim Jun‐Yeol , Lee Sang‐Cheon , Kim Eun‐Cheol 
Published: January 2015

ABSTRACTRecent reports suggest that hypoxia inducible factor‐2α (HIF‐2α) is a key regulator of osteoarthritis cartilage destruction. However, the precise role of HIF‐2α in the inflammatory response and osteoclast differentiation remains unclear. The purpose of this study was to investigate the effect of HIF‐2α on inflammatory cytokines, extracellular matrix (ECM) destruction enzymes, and osteoclastic differentiation in nicotine and lipopolysaccharide (LPS)‐stimulated human periodontal ligament cells (PDLCs). HIF‐2α was upregulated in chronically inflamed PDLCs of periodontitis patients, and in nicotine‐ and LPS‐exposed PDLC in dose‐ and time‐dependent manners. HIF‐2α inhibitor and HIF‐2α siRNA attenuated the nicotine‐ and LPS‐ induced production of NO and PGE2, upregulation of iNOS, COX‐2, pro‐inflammatory cytokines (IL‐1β, TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, IL‐11, and IL‐17), and matrix metalloproteinases (MMPs; MMP‐1, ‐8, ‐13, ‐2 and ‐9), and reversed the effect on TIMPs (TIMP‐1 and ‐2) in PDLCs. The conditioned medium produced by nicotine and LPS‐treated PDLCs increased the number of TRAP‐stained osteoclasts, TRAP activity and osteoclast‐specific genes, which has been blocked by HIF‐2α inhibition and silencing. HIF‐2α inhibitor and HIF‐2α siRNA inhibited the effects of nicotine and LPS on the activation of Akt, JAK2 and STAT3, ERK and JNK MAPK, nuclear factor‐κB, c‐Jun, and c‐Fos. Taken together, this study is the first to demonstrate that HIF‐2α inhibition exhibits anti‐inflammatory activity through the inhibition of inflammatory cytokines and impairment of ECM destruction, as well as blocking of osteoclastic differentiation in a nicotine‐ and periodontopathogen‐stimulated PDLCs model. Thus, HIF‐2α inhibition may be a novel molecular target for therapeutic approaches in periodontitis. J. Cell. Biochem. 116: 1241–1255, 2015. © 2015 Wiley Periodicals, Inc.
A Palaeodietary Study of Stable Isotope Analysis from a High‐status Burial in the Copper Age: The Montelirio Megalithic Structure at Valencina de la Concepción–Castilleja de Guzmán, Spain
Authors: Fontanals‐Coll M. , Díaz‐Zorita Bonilla M. , Subirà M. E. 
Published: January 2015

AbstractThis palaeodietary study presents carbon and nitrogen stable isotope data from human and faunal skeletal remains from the Copper Age settlement of Valencina de la Concepción–Castilleja de Guzmán, located in Seville, Spain. Montelirio, the only Valencina–Castilleja human group from which we have obtained reliable palaeodietary results, had a diet based on C3 terrestrial resources, including both plants and animals. The protein component of the diet consisted mainly of meat, milk and dairy products from livestock as well as C3 plant protein from cereals and pulses. This study compares data from Montelirio, the Copper Age group from Valencina–Castilleja, with the published data from other Iberian Late Neolithic–Copper Age (LN‐CA) societies. This comparison reveals a homogeneous diet with some exceptions. Overall, the LN‐CA diet in the Iberian Peninsula consisted mainly of animal proteins from meat, milk and dairy products from livestock as well as C3 plant sources from the characteristic agriculture of the societies of these periods. This study also demonstrates the minor use of aquatic resources from the Neolithic to the Copper Age period in the Iberian Peninsula. Copyright © 2015 John Wiley & Sons, Ltd.
Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma
Authors: Saiyin Hexige , Ardito‐Abraham Christine M , Wu Yanhua , Wei Youheng , Fang Yuan , Han Xu , Li Jianang , Zhou Ping , Yi Qing , Maitra Anirban , Liu Jun O , Tuveson David A , Lou Wenhui , Yu Long 
Published: January 2015

AbstractPancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma‐rich, vascular‐poor and hypo‐perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three‐dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair‐like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin‐rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter‐1 (GLUT‐1)‐positive vesicles. Clinically, as demonstrated by PET–CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT‐1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K‐Ras‐driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo‐ and exocytic properties, they may provide a non‐conventional method for cellular trafficking in PDAC tumours. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Safe and effective cryopreservation methods for long‐term storage of human‐amniotic‐fluid‐derived stem cells
Authors: Hennes Aurélie , Gucciardo Léonardo , Zia Silvia , Lesage Flore , Lefèvre Nicolas , Lewi Liesbeth , Vorsselmans Annick , Cos Teresa , Lories Rik , Deprest Jan , Toelen Jaan 
Published: January 2015

What's already known about this topic?

Stem cells can be isolated from amniotic fluid and may be used for cell therapy and tissue engineering applications in perinatal medicine.
Clinical implementation requires development of an adapted cell banking system including optimal processing and cryopreservation of amniotic fluid samples, with maintenance of cell viability and characteristics after thawing.What does this study add?

We identified three suitable cryopreservation protocols of fresh amniotic fluid samples with high cell recovery rate and unchanged stem cell characteristics post‐thawing.
One of these is compatible with current good manufacturing practice legislation and can be performed in fetal medicine units without stem cell culture expertise.
Synthesis, characterization, and solar cell and transistor applications of phenanthro[1,2‐b:8,7‐b′]dithiophene–Diketopyrrolopyrrole semiconducting polymers
Authors: Mori Hiroki , Suetsugu Masato , Nishinaga Shuhei , Chang Ning‐hui , Nonobe Hikaru , Okuda Yasuhiro , Nishihara Yasushi 
Published: January 2015

ABSTRACTSynthesis, characterization, and polymer solar cell and transistor application of a series of phenanthro[1,2‐b:8,7‐b′]dithiophene‐based donor–acceptor (D–A)‐type semiconducting polymers combined with a diketopyrrolopyrrole unit are reported. The present polymers showed some unique features such as strong aggregation behavior, high thermal stability, and short π–π stacking distance (3.5–3.6 Å), which are suitable for high performance organic materials. In addition, they have a significantly extended absorption up to 1000 nm with a band gap of ca. 1.2 eV. However, such strong intermolecular interaction reduced their solubility and molecular weights, which resulted in low crystalline nature and moderate field‐effect mobility of 0.01 cm2 V−1 s−1. Furthermore, such strong aggregation behavior led to the large‐scale phase separation in the blend films, which may prevent the effective photocurrent generation, limiting Jsc and power conversion efficiency of 2.0%. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 709–718
Structural insight into effector proteins of Gram‐negative bacterial pathogens that modulate the phosphoproteome of their host
Authors: Grishin Andrey M. , Beyrakhova Ksenia A. , Cygler Miroslaw 
Published: January 2015

AbstractInvading pathogens manipulate cellular process of the host cell to establish a safe replicative niche. To this end they secrete a spectrum of proteins called effectors that modify cellular environment through a variety of mechanisms. One of the most important mechanisms is the manipulation of cellular signaling through modifications of the cellular phosphoproteome. Phosphorylation/dephosphorylation plays a pivotal role in eukaryotic cell signaling, with ∼500 different kinases and ∼130 phosphatases in the human genome. Pathogens affect the phosphoproteome either directly through the action of bacterial effectors, and/or indirectly through downstream effects of host proteins modified by the effectors. Here we review the current knowledge of the structure, catalytic mechanism and function of bacterial effectors that modify directly the phosphorylation state of host proteins. These effectors belong to four enzyme classes: kinases, phosphatases, phospholyases and serine/threonine acetylases.
Inherent dynamics within the Crimean‐Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions
Authors: Eisenmesser Elan Z. , Capodagli Glenn C. , Armstrong Geoffrey S. , Holliday Michael J. , Isern Nancy G. , Zhang Fengli , Pegan Scott D. 
Published: January 2015

AbstractCrimean‐Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and remove ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) from numerous proteins involved in cellular signaling. Such manipulation of the host cell machinery serves to downregulate the host response and, therefore, complete characterization of these proteases is important. While several structures of the CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few structural differences have been found and little insight has been gained as to the structural plasticity of this protease. Therefore, we have used NMR relaxation experiments to probe the dynamics of CCHFV vOTU, both alone and in complex with Ub, discovering a highly dynamic protease that exhibits conformational exchange within the same regions found to engage its Ub substrate. These experiments reveal a structural plasticity around the N‐terminal regions of CCHFV vOTU, which are unique to vOTUs, and provide a rationale for engaging multiple substrates with the same binding site.
Quality of Life and Self-Determination: Youth with Chronic Health Conditions Make the Connection
Authors: McDougall Janette , Baldwin Patricia , Evans Jan , Nichols Megan , Etherington Cole , Wright Virginia 
Published: January 2015

AbstractWhile optimizing quality of life (QOL) is a key goal of rehabilitation care, no previous study has reported on what ‘QOL’ means to youth with chronic health conditions. In addition, no qualitative studies have explored the relationship between QOL and self-determination (SD). Objectives of this qualitative study were to examine: what the terms ‘quality of life’ and ‘self-determination’ mean to youth with chronic conditions; the factors these youth think are linked with these concepts; the relationship they see between concepts, the types of future goals youth have and how they view the connection between their SD and these goals. A descriptive methodology was used. A purposive sample of 15 youth aged 15 to 20 years was obtained. Youth had cerebral palsy, a central nervous system disorder, or autism spectrum disorder. Semi-structured interviews were conducted first, followed by a focus group. Line-by-line coding of transcripts was completed, codes were collapsed into categories, and themes identified. Participants viewed QOL as an overarching personal evaluation of their life, and used terms such as satisfaction and happiness to describe the concept. Factors related to QOL included: ‘relationships’, ‘supportive environments’, ‘doing things’, ‘personal growth and moving forward’, and ‘understanding of self/acceptance of disability’. Participants described SD in such terms as confidence and motivation. Contributors to SD were: ‘personal strengths’, ‘interdependence’, and ‘functional independence’. SD was considered important to QOL. Youth goals were reflective of the goals of most adolescents. They identified the importance of having key goals that were of personal interest to them. This study adds consumer-based information to the debate over the meaning of QOL. Service providers and decision makers should be aware of the factors that youth feel impact their QOL and SD, the importance of SD to youth QOL, and of SD to future goals, and consider this information when tailoring therapeutic interventions.
Self‐Aggregation of Catanionic Surface Active Ionic Liquids in Aqueous Solutions
Authors: Xu Wenwen , Zhang Qian , Wei Hongtu , Qin Jieqiong , Yu Li 
Published: January 2015

AbstractThe self‐aggregation behavior of catanionic surface active ionic liquids (SAIL), 1‐alkyl‐3‐methylimidazolium alkyl sulfates, [C4mim][C16SO4] and [C6mim][C14SO4], in aqueous solutions was explored by several techniques. These results were analyzed together with the concerning data of [C8mim][C12SO4] reported previously. The feature of these SAIL is that the total carbon number of the hydrophobic chains is kept constant, while only the length of the two hydrocarbon chains varies. Because of the different intermolecular and intramolecular interactions, the hydrophobic interaction of asymmetrical SAIL is enhanced, which explains the minimal CMC value of [C4mim][C16SO4]. Thermal motion of hydrocarbon chains at the air–water interface leads to higher Amin and lower Γmax values with the increasing asymmetry of two hydrophobic chains. The conductivity measurements reveal that the micellization process is spontaneous and entropy‐driven in the studied temperature range. This work indicates that the symmetry of alkyl chains can influence the aggregation behavior of [Cnmim][CmSO4] in aqueous solutions.