bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Systolic Dysfunction in Genotyped Hypertrophic Cardiomyopathy
Authors: Fujino Noboru , Konno Tetsuo , Hayashi Kenshi , Hodatsu Akihiko , Fujita Takashi , Tsuda Toyonobu , Nagata Yoji , Kawashiri Masa‐aki , Ino Hidekazu , Yamagishi Masakazu
Published: November 2012

Background:

Hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere, and approximately 5% of cases of HCM show systolic dysfunction with poor prognosis. Few data exist regarding the systolic dysfunction in a large population of genotyped HCM subjects.

Hypothesis:

The aim of this study was to assess the systolic dysfunction and prognosis in sarcomere gene mutation carriers.

Methods:

The study included 157 sarcomere gene mutation carriers from 69 unrelated HCM families (87 males; mean age, 46.5 ± 20.5 years). After exclusions for systolic dysfunction at baseline, 107 subjects underwent serial echocardiograms.

Results:

At a mean follow‐up of 7.0 years, 12 subjects experienced systolic dysfunction. In multivariate Cox analysis, systolic dysfunction was related to age and ejection fraction at initial evaluation (P < 0.001 and P = 0.020, respectively), and was associated with the absence of mutations in the cardiac myosin‐binding protein C gene (MYBPC3) (P = 0.042). When the subjects were divided into MYBPC3 and non‐MYBPC3 mutation carriers, and time from birth to development of systolic dysfunction was compared, the rate of systolic dysfunction was higher in the non‐MYBPC3 group than in MYBPC3 group (Kaplan‐Meier, log‐rank test, P = 0.010). After the onset of systolic dysfunction, 11 of 12 subjects died during a mean follow‐up of 8.3 years.

Conclusions:

Non‐MYBPC3 mutation carriers developed left ventricular systolic dysfunction more frequently than MYBPC3 mutation carriers, and the majority of sarcomere gene mutation carriers with systolic dysfunction had fatal outcomes during follow‐up. This suggests that subjects with mutations in sarcomeric genes require careful management for systolic dysfunction.

This work was supported in part by a Grant‐in‐Aid for Scientific Research, the Ministry of Education, Culture, Sports, Science, and Technology (KAKENHI 16790414, 19590807, 22590808, Tokyo, Japan), and the Research Grant for Cardiovascular Diseases (20C‐4) from the Ministry of Health, Labour, and Welfare (Tokyo, Japan).

The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Assessment of Urban Source Metal Levels in Influent, Effluent, and Sludge of Two Municipal Biological Nutrient Removal Wastewater Treatment Plants of Bursa, an Industrial City in Turkey
Authors: Salihoglu Nezih Kamil
Published: November 2012

Removal of Al, As, Cd, total Cr (Tot. Cr), Cu, Total Fe (Tot. Fe), Mn, Ni, Pb, Sb, Sn, and Zn from urban effluent by wastewater treatment plants (WWTPs) operated under five‐stage Bardenpho® process were investigated and water soluble metals in the dewatered sludge were quantified. Samples were collected from two WWTPs on a weekly basis over an approximately 2.5‐year time span. Tot. Fe and Al were the most abundant, As, Pb, Ni, Cu, and Cd were the least abundant metals in the influents of both WWTPs. Removal efficiencies above 75% were achieved for Tot. Cr, Tot. Fe, Al, and Cu, whereas, no significant removal was observed for As, Cd, Pb, Sb, and Sn. Removal of Tot. Cr, Cu, Tot. Fe, Zn, Al, Mn, and Ni were influenced by influent suspended solids concentrations, and of Tot. Cr, Zn, and Cd were influenced by their initial content in the influent. Zn removal efficiency of biological nutrient removal (BNR) system in this study was higher and Cd removal efficiency was lower than that of conventional activated sludge reported in the literature. No remarkable difference for metals such as Cu, Mn, Ni, and Pb was observed between the removal efficiencies of conventional system and BNR system.
A review of reporting systems and terminology for urine cytology
Authors: Owens Christopher L. , VandenBussche Christopher J. , Burroughs Frances H. , Rosenthal Dorothy L.
Published: November 2012

Urine cytology continues to play an important role in the diagnosis and management of urothelial carcinoma, a common cancer of adults with significant morbidity and mortality. Because of its high sensitivity for high‐grade urothelial tumors, including lesions that may be cystoscopically occult, urine cytology nicely compliments cystoscopic examination, a method that detects most low‐grade tumors. Over the decades, several reporting schemes for urine cytology have been published in the literature, each of which has relative strengths and weaknesses. Unlike cervical cytology, there has not been widespread acceptance and use of any particular reporting scheme for urine cytology studies. Thus, terminology and criteria for urine cytology reporting are not uniform among pathologists, which can frustrate clinicians and hinders interlaboratory comparisons. Cancer (Cancer Cytopathol) 2013;121:9–14 © 2012 American Cancer Society.
Secreted Factor R‐Spondin 2 is Involved in Refinement of Patterning of the Mammalian Cochlea
Authors: Mulvaney J. F. , Yatteau A. , Sun W. W. , Jacques B. , Takubo K. , Suda T. , Yamada W. , Dabdoub A.
Published: November 2012

Background: In the cochlea, patterning of the organ of Corti is tightly regulated to produce a single row of sound‐detecting inner hair cells and three rows of outer hair cells, which amplify and refine the signal. The recently identified R‐Spondin family of signaling molecules usually act as co‐activators of Wnt signaling; it is thought that they regulate turnover of Wnt receptors at the membrane. We sought to test whether R‐Spondins function in the developing cochlea. Results: Expression analysis of all four members of the R‐Spondin family showed that only R‐Spondin2 (Rspo2) is expressed in the cochlea during development of the sensory epithelium. Examination of an Rspo2−/− mouse showed that loss of Rspo2 results in an additional single row of outer hair cells and disruption of peripheral innervation pattern. Addition of Rspo2 recombinant protein to organotypic cochlear cultures resulted in a small but significant decrease in the number of outer hair cells. Conclusions: Rspo2 is required to limit the number of outer hair cells to three rows and for optimal arrangement of peripheral nerve fibers. The Rspo2 gain‐ and loss‐of‐function studies show that in the ear, Rspo2 function is not consistent with its assigned role as a Wnt potentiator. Developmental Dynamics 242:179–188, 2013. © 2012 Wiley Periodicals, Inc.
Use of quantitative habitat models for establishing performance metrics in river restoration planning
Authors: Parasiewicz Piotr , Ryan Kathleen , Vezza Paolo , Comoglio Claudio , Ballestero Thomas , Rogers Joseph N.
Published: November 2012

The ecological effectiveness and success of river restoration strongly depend on the resources invested in planning. Unfortunately, this trend of restoration engineering is frequently compromised by the application of qualitative assessment and resource intensive adaptive management processes. Habitat simulation models are effective tools for selecting ecologically effective restoration measures as part of the Environmental Benefits Analysis. Through the support from a mesohabitat simulation model, we identified three habitat metrics: (1) Habitat Quantity Deficiency; (2) Alteration of Habitat Structure; and (3) Habitat Stress Days Alteration to quantify and visualize differences between restoration options in Restoration Alternatives Assessment diagram. This concept of quantifying habitat models is supported by an example of application in the Wekepeke Brook in Massachusetts, in which the habitat metrics were used to define quantitative benchmarks, goals and targets to guide the restoration process from the design to the evaluation phase. The three habitat metrics are a cost effective alternative for evaluating the ecological benefits of a planned action. The methodology contributes to a high potential for designing and monitoring restoration projects. Copyright © 2012 John Wiley & Sons, Ltd.
NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short‐term IL‐2 activation
Authors: Vacca Paola , Martini Stefania , Garelli Valentina , Passalacqua Giovanni , Moretta Lorenzo , Mingari Maria Cristina
Published: November 2012

NK cells are a major component of innate immunity and exert a potent antitumor effect both in vitro and in vivo. However, NK cells infiltrating solid tumors have been shown to display severely impaired functional capabilities. In this study, we analyzed NK cells present in pleural effusions (PEs) of patients with primary or metastatic tumors of different origin, including mesothelioma and lung, breast, colon, gastric, bladder, and uterus carcinoma. In all instances, freshly isolated PE‐NK cells displayed a CD56bright phenotype and expressed normal levels of both activating receptors and HLA class I‐specific inhibitory receptors. In addition, they rapidly released large amounts of IFN‐γ and TNF‐α after stimulation. Upon culture in IL‐2, they acquired a potent cytolytic activity against both allogeneic and autologous tumor cells. Tumor cell lysis was primarily mediated by NKG2D and NKp30 and partially by NKp46 and DNAM‐1, in agreement with the expression of the corresponding ligands on tumor cells. The finding that PE‐NK cells are not functionally impaired and that they can efficiently kill tumor cells upon short‐term IL‐2 activation may offer important clues for the development of novel approaches in tumor immunotherapy.
Crystallization and melting properties of extra virgin olive oil studied by synchrotron XRD and DSC
Authors: Barba Luisa , Arrighetti Gianmichele , Calligaris Sonia
Published: November 2012

Crystallization and melting properties of triacylglycerols in extra virgin olive oil were studied by using synchrotron X‐ray diffraction (XRD) and differential scanning calorimetry (DSC). The phase transitions were monitored by cooling and heating the samples at 2°C/min from 60 to −60°C and vice versa. Upon cooling, a first DSC endothermic peak was recorded at −9.6°C followed by one at −33.5°C. These thermal events were associated to the formation of two different structures: a triple‐chain length (3L) having a c parameter of about 58.38 Å and a quadruple chain length structure (4L) with a c parameter of about 89.99 Å, respectively. Both structures evidenced a cell packing arrangement ascribable to a β′ form. During heating, part of the metastable β′ crystals rearranged into the more thermodynamically stable β form. Then, upon further heating, the sequential melting of the two crystal structures was observed. The melting was completed at 10.7°C. Beside this interpretation of XRD data, a model considering a cell with a c parameter of about 170 Å and a hexagonal crystal system was proposed. Even if more research is needed to validate this approach, it allowed all XRD events recorded during the experiments to be described.

See commentary by Chiavaro [p. 267–269], http://dx.doi.org/10.1002/ejlt.201200415
Chemoenzymatic Asymmetric Total Synthesis of (R)‐Lasiodiplodin Methyl Ether through a Sulfatase‐Based Deracemization Process
Authors: Fuchs Michael , Toesch Michael , Schober Markus , Wuensch Christiane , Faber Kurt
Published: November 2012

(R)‐Lasiodiplodin methyl ether, a precursor of the antileukemic agent lasiodiplodin, was synthesized through a seven‐step linear sequence. Chirality was introduced through a sulfatase‐based deracemization process, in which a functionalized (rac)‐sec‐sulfate ester was enzymatically hydrolyzed with inversion of the stereocenter using an alkyl sulfatase. The remaining sulfate ester enantiomer was hydrolyzed with retention of configuration under acidic conditions, yielding the chiral key building block as the sole product in 93 % ee The total synthesis was completed through Negishi cross‐coupling and ring‐closing metathesis.
Palladium‐Catalyzed Base‐Free Suzuki–Miyaura Coupling Reactions of Fluorinated Alkenes and Arenes via a Palladium Fluoride Key Intermediate
Authors: Ohashi Masato , Saijo Hiroki , Shibata Mitsutoshi , Ogoshi Sensuke
Published: November 2012

A new strategy for C–C bond formation with organoboronates through C–F activation of fluorinated alkenes and arenes was developed. In this Pd‐catalyzed Suzuki–Miyaura‐type cross‐coupling reaction, neither a base for enhancing the reactivity of the organoboron reagents nor a Lewis acid for promoting C–F bond activation was required. A fluoropalladium intermediate played an essential role in this reaction. In addition, a Ni(NHC) catalyst was efficient for C–C coupling through C–F bond activation of fluoroarenes.
Formation of MSeO4(aq) complexes (M2+ = Mg2+, Co2+, Ni2+, Cu2+, Cd2+) studied as a function of temperature by affinity capillary electrophoresis
Authors: Philippini Violaine , Aupiais Jean , Vercouter Thomas
Published: November 2012

Complexation of divalent cations (Mg2+, Co2+, Ni2+, Cu2+, Cd2+) by selenate ligand was studied by ACE (UV indirect detection) in 0.1 mol/L NaNO3 ionic strength solutions at various temperatures (15, 25, 35, 45 and 55°C). For each solution, a unique peak was observed as a result of a fast equilibrium between the free ion and the complex (labile systems). The migration time corresponding to this peak changed as a function of the solution composition, namely the free and complexed metal concentrations, according to the complexation reactions. The results confirmed the formation of a unique 1:1 complex for each cation. The thermodynamic parameters were fitted to the experimental data at 0.1 mol/L ionic strength: (25°C) = −(6.5 ± 0.3), −(7.5 ± 0.3), −(7.7 ± 0.3), −(7.7 ± 0.3), and –(8.1 ± 0.3) kJ/mol and = 2.5 ± 0.2, 4.7 ± 0.4, 4.5 ± 0.6, 8.4 ± 1.1, and 7.2 ± 0.6 kJ/mol for M2+ = Mg2+, Co2+, Ni2+, Cu2+, and Cd2+, respectively. Complexes with alkaline earth and transition metal cations could be distinguished by their relative stabilities. The effect of the ionic medium was treated using the specific ion interaction theory and the thermodynamic parameters at infinite dilution were compared to previously published data on metal–selenate, metal–sulfate, and metal–chromate complexes.
Evaluation of gene expression changes in human primary uroepithelial cells following 24‐Hr exposures to inorganic arsenic and its methylated metabolites
Authors: Yager Janice W. , Gentry P. Robinan , Thomas Russell S. , Pluta Linda , Efremenko Alina , Black Michael , Arnold Lora L. , McKim James M. , Wilga Paul , Gill Gary , Choe Key‐Young , Clewell Harvey J.
Published: November 2012

Gene expression changes in primary human uroepithelial cells exposed to arsenite and its methylated metabolites were evaluated to identify cell signaling pathway perturbations potentially associated with bladder carcinogenicity. Cells were treated with mixtures of inorganic arsenic and its pentavalent or trivalent metabolites for 24 hr at total arsenic concentrations ranging from 0.06 μM to 18 μM. One series (five samples) was conducted with arsenite and pentavalent metabolites and a second (10 samples) with arsenite and trivalent metabolites. Similar gene expression responses were obtained for pentavalent or trivalent metabolites. A suite of eight gene changes was consistently identified across individuals that reflect effects on key signaling pathways: oxidative stress, protein folding, growth regulation, metallothionine regulation, DNA damage sensing, thioredoxin regulation, and immune response. No statistical significance of trend (NOSTASOT) analysis of these common genes identified lowest observed effect levels (LOELs) from 0.6 to 6.0 μM total arsenic and no observed effect levels (NOELs) from 0.18 to 1.8 μM total arsenic. For the trivalent arsenical mixture, benchmark doses (BMDs) ranged from 0.13 to 0.92 μM total arsenic; benchmark dose lower 95% confidence limits (BMDLs) ranged from 0.09 to 0.58 μM total arsenic. BMDs ranged from 0.53 to 2.7 μM and BMDLs from 0.35 to 1.7 μM for the pentavalent arsenical mixture. Both endpoints varied by a factor of 3 across individuals. Thisstudy is the first to examine gene expression response in primary uroepithelial cells from multiple individuals and to identify no effect levels for arsenical‐induced cell signaling perturbations in normal human cells exposed to a biologically plausible concentration range. © Environ. Mol. Mutagen., 2013. © 2012 Wiley Periodicals, Inc.
High Performance by Applying IrCo/C Nanoparticles as an Anode Catalyst for PEMFC
Authors: Yang D. , Li B. , Zhang H. , Ma J.
Published: November 2012

IrCo bimetallic anode catalysts for polymer electrolyte membrane fuel cell (PEMFC) have been synthesized with a modified ethylene glycol method. X‐ray diffraction, TEM, CV, and linear sweep voltammetry results show that after the modification of Co, Ir nanoparticles supported on carbon exhibit high activity for hydrogen oxidation reaction (HOR). The maximum power density of 610.5 mW cm–2 of a 50 cm2 single cell is achieved using 20%Ir–30%Co/C catalyst as the anode, with a loading of 0.2  mgIr cm–2. It is suggested that IrCo/C proposed in this work may be used as anode catalyst of PEMFC.
Toward Fully‐ and Semi‐passive Operation of a Liquid‐Fed Direct Methanol Fuel Cell
Authors: Yuan W. , Tang Y. , Yang X. , Wan Z.
Published: November 2012

This work reports the performance characteristics of a liquid‐fed direct methanol fuel cell (DMFC) operated in both fully‐ and semi‐passive conditions. For the latter case, a blower is used to provide forced air convection at the cathode so as to reveal how and how much a passive DMFC suffers from its structural constraint and also the mass and heat transfer limitations. The results based on the fully passive operation suggest that the cell performance is greatly affected by the level of methanol concentration. In this study, 2 M performs the best when the cell uses different structural setups. Besides, the effects of ambient temperature and the cathode self‐heating mechanisms are also explored under a fully passive condition. For the semi‐passive operation, forced air convection is proved to be helpful in enhancing oxygen delivery but may lead to faster heat and water dissipation and thus significantly reduces the cell performance. An optimal blowing intensity is obtained when the blower operates at a half speed. When the cathode diffusion layer is removed, the effects of active air supply become weakened. Considering the limited performance improvement and parasitic losses caused by a blower, we believe the self‐breathing mode is still an attractive choice.
ACCOUNTING FOR PRODUCT SUBSTITUTION IN THE ANALYSIS OF FOOD TAXES TARGETING OBESITY
Authors: Miao Zhen , Beghin John C. , Jensen Helen H.
Published: November 2012

We extend the existing literature on food taxes targeting obesity. We systematically incorporate the implicit substitution between added sugars and solid fats into a comprehensive food demand system and evaluate the effect of taxes on sugars and fats. The approach conditions how food and obesity taxes affect total calorie intake. The proposed methodology accounts for the ability of consumers to substitute leaner low‐fat and low‐sugar items for rich food items within the same food group. We calibrate this demand system approach using recent food intake data and existing estimates of price and income elasticities of demand. The demand system accounts for both the within‐food group substitution and the substitution across these groups. Simulations of taxes on added sugars and solid fat show that the tax impact on consumption patterns is understated and the induced welfare loss is overstated when not allowing for the substitution possibilities within food groups. Copyright © 2012 John Wiley & Sons, Ltd.
Endoplasmic reticulum polymers impair luminal protein mobility and sensitize to cellular stress in alpha1-antitrypsin deficiency
Authors: Ordóñez Adriana , Snapp Erik L. , Tan Lu , Miranda Elena , Marciniak Stefan J. , Lomas David A.
Published: November 2012

Point mutants of alpha1-antitrypsin (α1AT) form ordered polymers that are retained as inclusions within the endoplasmic reticulum (ER) of hepatocytes in association with neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. These inclusions cause cell damage and predispose to ER stress in the absence of the classical unfolded protein response (UPR). The pathophysiology underlying this ER stress was explored by generating cell models that conditionally express wild-type (WT) α1AT, two mutants that cause polymer-mediated inclusions and liver disease (E342K [the Z allele] and H334D) and a truncated mutant (Null Hong Kong; NHK) that induces classical ER stress and is removed by ER-associated degradation. Expression of the polymeric mutants resulted in gross changes in the ER luminal environment that recapitulated the changes observed in liver sections from individuals with PI*ZZ α1AT deficiency. In contrast, expression of NHK α1AT caused electron lucent dilatation and expansion of the ER throughout the cell. Photobleaching microscopy in live cells demonstrated a decrease in the mobility of soluble luminal proteins in cells that express E342K and H334D α1AT, when compared to those that express WT and NHK α1AT (0.34 ± 0.05, 0.22 ± 0.03, 2.83 ± 0.30, and 2.84 ± 0.55 μm2/s, respectively). There was no effect on protein mobility within ER membranes, indicating that cisternal connectivity was not disrupted. Polymer expression alone was insufficient to induce the UPR, but the resulting protein overload rendered cells hypersensitive to ER stress induced by either tunicamycin or glucose depletion.

Conclusion :

Changes in protein diffusion provide an explanation for the cellular consequences of ER protein overload in mutants that cause inclusion body formation and α1AT deficiency.
DAG‐sensitive and Ca2+ permeable TRPC6 channels are expressed in dentate granule cells and interneurons in the hippocampal formation
Authors: Nagy Gergő A. , Botond Gergő , Borhegyi Zsolt , Plummer Nicholas W. , Freund Tamás F. , Hájos Norbert
Published: November 2012

Members of the transient receptor potential (TRP) cation channel family play important roles in several neuronal functions. To understand the precise role of these channels in information processing, their presence on neuronal elements must be revealed. In this study, we investigated the localization of TRPC6 channels in the adult hippocampal formation. Immunostainings with a specific antibody, which was validated in Trpc6 knockout mice, showed that in the dentate gyrus, TRPC6 channels are strongly expressed in granule cells. Immunogold staining revealing the subcellular localization of TRPC6 channels clarified that these proteins were predominantly present on the membrane surface of the dendritic shafts of dentate granule cells, and also in their axons, often associated with intracellular membrane cisternae. In addition, TRPC6 channels could be observed in the dendrites of some interneurons. Double immunofluorescent staining showed that TRPC6 channels were present in the dendrites of hilar interneurons and hippocampal interneurons with horizontal dendrites in the stratum oriens expressing mGlu1a receptors, whereas parvalbumin immunoreactivity was revealed in TRPC6‐expressing dendrites with radial appearance in the stratum radiatum. Electron microscopy showed that the immunogold particles depicting TRPC6 channels were located on the surface membranes of the interneuron dendrites. Our results suggest that TRPC6 channels are in a key position to alter the information entry into the trisynaptic loop of the hippocampal formation from the entorhinal cortex, and to control the function of both feed‐forward and feed‐back inhibitory circuits in this brain region. © 2012 Wiley Periodicals, Inc.
Resonance Raman based skin carotenoid measurements in newborns and infants
Authors: Ermakov Igor V. , Ermakova Maia R. , Bernstein Paul S. , Chan Gary M. , Gellermann Werner
Published: November 2012

We describe Resonance Raman based skin carotenoid measurements in newborns and infants. Skin‐ and serum carotenoid levels correlate with high statistical significance in healthy newborns and infants, and with reduced accuracy also in prematurely born infants, who in general feature very low carotenoid levels and thin transparent skin giving rise to large background absorption effects. Skin carotenoid levels can be easily compared among subjects and/or tracked in longitudinal studies with the highly molecule‐specific Raman method. It therefore holds promise as a rapid, non‐invasive, carotenoid antioxidant assessment method for newborns and infants in the field of pediatrics. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The heterogeneity in femoral neck structure and strength
Authors: Kersh Mariana E , Pandy Marcus G , Bui Quang M , Jones Anthony C , Arns Christoph H , Knackstedt Mark A , Seeman Ego , Zebaze Roger MD
Published: November 2012

Most measures of femoral neck strength derived using dual-energy X-ray absorptiometry or computed tomography (CT) assume the femoral neck is a cylinder with a single cortical thickness. We hypothesized that these simplifications introduce errors in estimating strength and that detailed analyses will identify new parameters that more accurately predict femoral neck strength. High-resolution CT data were used to evaluate 457 cross-sectional slices along the femoral neck of 12 postmortem specimens. Cortical morphology was measured in each cross-section. The distribution of cortical thicknesses was evaluated to determine whether the mean or median better estimated central tendency. Finite-element models were used to calculate the stresses in each cross-section resulting from the peak hip joint forces created during a sideways fall. The relationship between cortical morphology and peak bone stress along the femoral neck was analyzed using multivariate regression analysis. In all cross-sections, cortical thicknesses were non-normally distributed and skewed toward smaller thicknesses (p < 0.0001). The central tendency of cortical thickness was best estimated by the median, not the mean. Stress increased as the median cortical thickness decreased along the femoral neck. The median, not mean, cortical thickness combined with anterior-posterior diameter best predicted peak bone stress generated during a sideways fall (R2 = 0.66, p < 0.001). Heterogeneity in the structure of the femoral neck determines the diversity of its strength. The median cortical thickness best predicted peak femoral neck stress and is likely to be a relevant predictor of femoral neck fragility. © 2013 American Society for Bone and Mineral Research.
Depletion of β‐arrestin2 in hepatic stellate cells reduces cell proliferation via ERK pathway
Authors: Sun Wu‐Yi , Song Yang , Hu Shan‐Shan , Wang Qing‐Tong , Wu Hua‐Xun , Chen Jing‐Yu , Wei Wei
Published: November 2012

β‐Arrestins are multifunctional adaptor proteins. Recently, some new roles of β‐arrestins in regulating intracellular signaling networks have been discovered, which regulate cell growth, proliferation, and apoptosis. Though, the role of β‐arrestins expression in the pathology of hepatic fibrosis remains unclear. In this study, the possible relationship between the expression of β‐arrestins with the experimental hepatic fibrosis and the proliferation of hepatic stellate cells (HSCs) were investigated. Porcine serum induced liver fibrosis was established in this study. At five time points, the dynamic expression of β‐arrestin1, β‐arrestin2, and α‐smooth muscle actin (α‐SMA) in rat liver tissues, was measured by immunohistochemical staining, double immunofluorescent staining, and Western blotting. This study showed that aggravation of hepatic fibrosis with gradually increasing expression of β‐arrestin2 in the hepatic tissues, but not β‐arrestin1. Further, as hepatic fibrosis worsens, β‐arrestin2‐expressing activated HSCs accounts for an increasingly larger percentage of all activated HSCs. And the expression of β‐arrestin2 had a significant positive correlation with the expression of α‐SMA, an activated HSCs marker. In vitro studies, the dynamic expression of β‐arrestin1 and β‐arrestin2 in platelet derived growth factor‐BB (PDGF‐BB) stimulated HSCs was assessed by Western blotting. The expression of β‐arrestin2 was remarkably increased in PDGF‐BB stimulated HSCs. Furthermore, the small interfering RNA (siRNA) technique was used to explore the effect of β‐arrestins on the proliferation of HSCs and the activation of ERK1/2. Transfection of siRNA targeting β‐arrestin2 mRNA (siβ‐arrestin2) into HSCs led to a 68% and 70% reduction of β‐arrestin2 mRNA and protein expression, respectively. siβ‐arrestin2 abolished the effect of PDGF‐BB on the proliferation of HSCs. In addition, siβ‐arrestin2 exerted the inhibition of the activation of ERK1/2 in HSCs. The present study provided strong evidence for the participation of the β‐arrestin2 in the pathogenesis of hepatic fibrosis. The β‐arrestin2 depletion diminishes HSCs ERK1/2 signaling and proliferation stimulated by PDGF‐BB. Selective targeting of β‐arrestin2 inhibitors to HSCs might present as a novel strategy for the treatment of hepatic fibrosis. J. Cell. Biochem. 114: 1153–1162, 2013. © 2012 Wiley Periodicals, Inc.
Polyphenols suppress hydrogen peroxide‐induced oxidative stress in human bone‐marrow derived mesenchymal stem cells
Authors: Yagi Haruyo , Tan Jian , Tuan Rocky S.
Published: November 2012

Human mesenchymal stem cells (hMSCs) are considered a highly promising candidate cell type for cell‐based tissue engineering and regeneration because of their self‐renewal and multi‐lineage differentiation characteristics. Increased levels of reactive oxygen/nitrogen species (ROS/RNS) are associated with tissue injury and inflammation, impact a number of cellular processes, including cell adhesion, migration, and proliferation, and have been linked to cellular senescence in MSCs, potentially compromising their activities. Naturally occurring polyphenolic compounds (polyphenols), epigallocatechin‐3‐gallate (EGCG), and curcumin, block ROS/RNS and are potent inflammation‐modulating agents. However, their potential protective effects against oxidative stress in hMSCs have not been examined. In this study, we carried out a systematic analysis of the effects of polyphenols on hMSCs in their response to oxidative stress in the form of treatment with H2O2 and S‐nitroso‐N‐acetylpenicillamine (SNAP), respectively. Parameters measured included colony forming activity, apoptosis, and the levels of antioxidant enzymes and free reactive species. We found that polyphenols reversed H2O2‐induced loss of colony forming activity in hMSCs. In a dose‐dependent manner, polyphenols inhibited increased levels of ROS and NO, produced by H2O2 or SNAP, respectively, in MSCs. Notably, polyphenols rapidly and almost completely blocked H2O2‐induced ROS in the absence of significant direct effect on H2O2 itself. Polyphenols also protected the antioxidant enzymes and reduced apoptotic cell death caused by H2O2 exposure. Taken together, these findings demonstrate that EGCG and curcumin are capable of suppressing inducible oxidative stress in hMSCs, and suggest a possible new approach to maintain MSC viability and potency for clinical application. J. Cell. Biochem. 114: 1163–1173, 2013. © 2012 Wiley Periodicals, Inc.
ATDC5: An excellent in vitro model cell line for skeletal development
Authors: Yao Yongchang , Wang Yingjun
Published: November 2012

The ATDC5 cell line is derived from mouse teratocarcinoma cells and characterized as a chondrogenic cell line which goes through a sequential process analogy to chondrocyte differentiation. Thus, it is regarded as a promising in vitro model to study the factors that influence cell behaviors during chondrogenesis. It also provides insights in exploring signaling pathways related to skeletal development as well as interactions with innovative materials. To date, over 200 studies have utilized ATDC5 to obtain lots of significant findings. In this review, we summarized the literature of ATDC5 related studies and emphasized the application of ATDC5 in chondrogenesis. In addition, the general introduction of ATDC5 including its derivation and characterization is covered in this article. J. Cell. Biochem. 114: 1223–1229, 2013. © 2012 Wiley Periodicals, Inc.
Coulomb replica‐exchange method: Handling electrostatic attractive and repulsive forces for biomolecules
Authors: Itoh Satoru G. , Okumura Hisashi
Published: November 2012

We propose a new type of the Hamiltonian replica‐exchange method (REM) for molecular dynamics (MD) and Monte Carlo simulations, which we refer to as the Coulomb REM (CREM). In this method, electrostatic charge parameters in the Coulomb interactions are exchanged among replicas while temperatures are exchanged in the usual REM. By varying the atom charges, the CREM overcomes free‐energy barriers and realizes more efficient sampling in the conformational space than the REM. Furthermore, this method requires only a smaller number of replicas because only the atom charges of solute molecules are used as exchanged parameters. We performed Coulomb replica‐exchange MD simulations of an alanine dipeptide in explicit water solvent and compared the results with those of the conventional canonical, replica exchange, and van der Waals REMs. Two force fields of AMBER parm99 and AMBER parm99SB were used. As a result, the CREM sampled all local‐minimum free‐energy states more frequently than the other methods for both force fields. Moreover, the Coulomb, van der Waals, and usual REMs were applied to a fragment of an amyloid‐β peptide (Aβ) in explicit water solvent to compare the sampling efficiency of these methods for a larger system. The CREM sampled structures of the Aβ fragment more efficiently than the other methods. We obtained β‐helix, α‐helix, 310‐helix, β‐hairpin, and β‐sheet structures as stable structures and deduced pathways of conformational transitions among these structures from a free‐energy landscape. © 2012 Wiley Periodicals, Inc.
Insight into microbial hemicellulases other than xylanases: a review
Authors: Juturu Veeresh , Wu Jin Chuan
Published: November 2012

Hemicellulases responsible for depolymerization of hemicellulose, including α‐glucuronidase, α‐arabinofuranosidase, arabinase, endo‐mannanase, β‐mannosidase, acetyl xylan esterase and feruloyl xylan esterase, were reviewed. They usually exist as multimers with a modified (β/α)8 Tim barrel fold. In a few cases they possess a substrate binding domain which helps them bind to the substrates bringing efficient hydrolysis. Post‐translational modifications are the major reasons leading to enzyme multiplicities to adapt the heterogeneous nature of hemicellulose. Glycosylation is one of the most important post translational modifications and contributes multiple functions to the protein such as stability, multiplicity and in a few cases enzyme activity. Advances in recombinant DNA technology have made it feasible to clone, improve and functionally express them in various hosts. Hemicellulases are traditionally applied in food, feed, detergent and paper industries, but their applications in hydrolysis of hemicellulose to release sugars is expected to increase, driven by the rapid development of lignocellulose biorefineries. Screening more powerful hemicellulases from nature, mining their coding genes from various sources and engineering them genetically are recommended for broadening their applications. © 2012 Society of Chemical Industry
Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia
Authors: Harris Ashley D. , Roberton Victoria H. , Huckle Danielle L. , Saxena Neeraj , Evans C. John , Murphy Kevin , Hall Judith E. , Bailey Damian M. , Mitsis Georgios , Edden Richard A.E. , Wise Richard G.
Published: November 2012

Purpose:

To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using magnetic resonance spectroscopy (MRS) during hypoxia.

Materials and Methods:

A respiratory protocol consisting of 10‐minute baseline normoxia, 20‐minute inspiratory hypoxia, and ending with 10‐minute normoxic recovery was used, throughout which lactate‐edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end‐tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge.

Results:

The average lactate increase was 20% ± 15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400 seconds. The average relative increase in blood lactate was 188% ± 95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200‐second time bins of MRS data (coefficient of variation 0.063 ± 0.035 between time bins in normoxia). The across‐subject coefficient of variation was 0.333.

Conclusion:

The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain's response to hypoxia. J. Magn. Reson. Imaging 2013;37:739–745. © 2012 Wiley Periodicals, Inc.
Prevalence of Antibodies to Hepatitis E Virus in Immigrants: A Seroepidemiological Survey in the District of Foggia (Apulia‐Southern Italy)
Authors: Scotto Gaetano , Martinelli Domenico , Giammario Adele , Prato Rosa , Fazio Vincenzina
Published: November 2012

Hepatitis E virus (HEV) is the etiologic agent of endemically transmitted viral hepatitis. HEV is endemic in developing countries where it occurs in sporadic and endemic forms, but autochthonous sporadic cases of hepatitis E have been reported in North America and in Europe, including Italy. The aim of the present study was to assess the seroprevalence of antibodies to HEV in immigrants from developing countries to the province of Foggia. The seroprevalence of HEV was determined in a cohort of 412 immigrants (mostly from countries in sub‐Saharan Africa) who had arrived recently in Italy. Serum samples were tested for anti‐HEV by a commercial enzyme immunoassay (EIA) based on recombinant proteins; positive results were confirmed by a Western blot assay (Recomblot HEV). A total of 88 (21.3%) of the 412 serum samples examined were reactive to IgG anti‐HEV. Eighty‐one of these samples (19.7%) were confirmed by Western blot. Anti‐HEV IgM was found in 34/81 subjects (41.9%) of the anti‐HEV IgG positive serum samples. Almost all anti‐HEV positive subjects were asymptomatic clinically, but alanine aminotransferase serum values were elevated in 28/34 (82.3%) patients with IgM anti‐HEV‐positive. The results of this study indicate high circulation of HEV in the immigrant population. The high prevalence of acute hepatitis involved mainly subjects who arrived in Italy during the same period from the same countries (Eritrea, Ethiopia, and Somalia). J. Med. Virol. 85:261–265, 2013. © 2012 Wiley Periodicals, Inc.
Effect of rhBMP‐2 and VEGF in a vascularized bone allotransplant experimental model based on surgical neoangiogenesis
Authors: Mattar Tiago , Friedrich Patricia F. , Bishop Allen T.
Published: November 2012

We have demonstrated survival of living allogeneic bone without long‐term immunosuppression using short‐term immunosuppression and simultaneous creation of an autogenous neoagiogenic circulation. In this study, bone morphogenic protein‐2 (rhBMP‐2), and/or vascular endothelial growth factor (VEGF), were used to augment this process. Femoral diaphyseal bone was transplanted heterotopically from 46 Dark Agouti to 46 Lewis rats. Microvascular repair of the allotransplant nutrient pedicle was combined with intra‐medullary implantation of an autogenous saphenous arteriovenous (AV) bundle and biodegradable microspheres containing buffer (control), rhBMP‐2 or rhBMP‐2 + VEGF. FK‐506 given daily for 14 days maintained nutrient pedicle flow during angiogenesis. After an 18 weeks survival period, we measured angiogenesis (capillary density) from the AV bundle and cortical bone blood flow. Both measures were greater in the combined (rhBMP‐2 + VEGF) group than rhBMP‐2 and control groups (p < 0.05). Osteoblast counts were also higher in the rhBMP‐2 + VEGF group (p < 0.05). A trend towards greater bone formation was seen in both rhBMP2 + VGF and rhBMP2 groups as compared to controls (p = 0.059). Local administration of VEGF and rhBMP‐2 augments angiogenesis, osteoblastic activity and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 561–566, 2013
Evaluation of factors affecting tibial bone strain after unicompartmental knee replacement
Authors: Pegg Elise C. , Walter Jonathan , Mellon Stephen J. , Pandit Hemant G. , Murray David W. , D'Lima Darryl D. , Fregly Benjamin J. , Gill Harinderjit S.
Published: November 2012

Persistent pain is an important cause of patient dissatisfaction after unicompartmental knee replacement (UKR) and has been correlated with localized tibial strain. However, the factors that influence these strains are not well understood. To address this issue, we created finite element models to examine the effect on tibial strain of: (1) muscle forces (estimated using instrumented knee data) acting on attachment sites on the proximal tibia, (2) UKR implantation, (3) loading position, and (4) changes in gait pattern. Muscle forces acting on the tibia had no significant influence on strains within the periprosthetic region, but UKR implantation increased strain by 20%. Strain also significantly increased if the region of load application was moved >3 mm medially. The strain within the periprosthetic region was found to be dependent on gait pattern and was influenced by both medial and lateral loads, with the medial load having a greater effect (regression coefficients: medial = 0.74, lateral = 0.30). These findings suggest that tibial strain is increased after UKR and may be a cause of pain. It may be possible to reduce pain through modification of surgical factors or through altered gait patterns. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 821–828, 2013
Chemical analysis of Teucrium species (Lamiaceae) growing on serpentine soils in Bulgaria
Authors: Pavlova Dolja , Karadjova Irina
Published: November 2012

Trace elemental concentrations (Fe, Ni, Mn, Cr, Co, Cu, Zn, Pb, Cd, and As) in aerial biomass (stems, leaves, and flowers) of the medicinal plants Teucrium chamaedrys, T. montanum, and T. polium growing on serpentine soils in Bulgaria were examined in relation to the total element contents in their respective rhizospheric soils. The objectives of the study were to evaluate: (1) elemental concentrations in plant tissues and associated soil samples together with the plants ability to tolerate/accumulate metal concentrations; (2) correlations between total metal concentrations in plants and their rhizospheric soils. Metal concentrations varied across species and sites. Their levels in plant tissues from nonserpentine sites were always lower compared to those from serpentine ones. The highest concentrations for Fe, Ni, Mn, Cr, As, Cu, and Pb were found in T. polium. Positive correlation coefficients were established between Ni, Cr, Fe, Co, and Cu in plants and Ca in the soil. None of the species tested hyperaccumulated metals although the metal concentration in some of them exceeded the range naturally found in plants. The Teucrium species can be considered as “excluders”, containing relatively low metal concentrations in their aerial parts (stems, leaves, and flowers) even in cases of high elemental concentrations in the rhizospheric soil. In all three medicinal plants, metal concentrations for toxic elements were above the permissible limits for pharmaceutical purposes. Therefore, plants found on serpentine bedrock are not recommended to be collected for pharmaceutical purposes.
Effects of lanthanum on growth, element uptake, and oxidative stress in rice seedlings
Authors: Liu Dongwu , Lin Yousheng , Wang Xue
Published: November 2012

We assessed the effects of increasing amounts of lanthanum (La) in solution on growth, nutrient metal accumulation, and the expression of oxidative stress in rice seedlings. The La concentration in shoots increased with La3+ supply and differentially affected the uptake of nutrient elements. Hormetic effects were observed on seed germination and biomass accumulation with increasing trends up to 0.1 mM La3+. Higher La concentrations were associated with an increase in malondialdehyde and H2O2 and a decline in chlorophyll, soluble proteins, and photosynthetic activity. We conclude that La supply at low rates may be beneficial to rice, while at higher rates, La induces oxidative stress.
Rhizosphere phosphorus depletion by three crops differing in their phosphorus critical levels
Authors: Rubio Gerardo , Faggioli Valeria , Scheiner Javier D. , Gutiérrez‐Boem Flavio H.
Published: November 2012

It has been reported for many soils that maize (Zea mays L.) has a higher soil‐P critical level than soybean (Glycine max L.) and sunflower (Helianthus annuus L). The objective of this work was to compare the rhizosphere P depletion in these three species in order to investigate if they differ in their capacity to acquire soil P. Sequential P fractionation and pH were determined in rhizosphere and nonrhizosphere soil samples from field and greenhouse experiments. Neither sunflower (the species with highest rhizosphere acidification) nor soybean or maize showed a significant relationship between P depletion and rhizosphere pH. The labile P fraction and the NaOH‐Pi fraction had lower values in the rhizosphere than in the bulk soil in 38% and 77% of the studied cases, respectively. Sunflower and especially maize presented a more intense Pi depletion than soybean. The comparison between sunflower and maize revealed that neither of them took a clear advantage over the other in terms of P depletion. Rhizosphere Pi depletion was associated with the amount of P acquired by the plants. We conclude that the accessibility to different P pools does not explain the differences in soil‐P critical levels among the three species.
Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non‐small cell lung cancer: Differences according to histology and smoking status
Authors: Kato Tatsuya , Ishikawa Keidai , Aragaki Masato , Sato Masaaki , Okamoto Kenzo , Ishibashi Tetsuya , Oba Koji , Kaji Mitsuhito
Published: November 2012

Background

The cutoff value of preoperative serum carcinoembryonic antigen (CEA) levels has not been investigated using appropriate subgroup analyses for non‐small cell lung carcinoma (NSCLC). This study was undertaken to determine whether the most predictive preoperative CEA level for risk of recurrence differs according to histological type, and how smoking status influences predictive values in Stage I NSCLC.

Methods

Subjects comprised Stage I NSCLC patients [141 patients with adenocarcinoma (ADC) and 36 with squamous cell carcinoma (SCC)].

Results

In patients with Stage I ADC, recurrence‐free survival (RFS) differed most significantly at a preoperative CEA level of 2.5 ng/ml, regardless of smoking status. Cases with preoperative CEA >2.5 ng/ml correlated with male sex, high maximum standard uptake value on 18F‐fluorodeoxyglucose positron emission tomography, poorer histopathological grade, lymphatic invasion, and smoking status. Importantly, preoperative CEA >2.5 ng/ml was identified as an independent risk factor for recurrence (P = 0.0015). Conversely, in patients with SCC, a preoperative CEA level of 3.0 ng/ml was the most predictive threshold.

Conclusions

Thresholds of preoperative CEA should be considered when predicting risk of relapse, even if these levels are within normal limits, as optimal cutoff levels may vary according to histological type. J. Surg. Oncol. 2013;107:619–624. © 2012 Wiley Periodicals, Inc.