bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeography of the Mekong mud snake (Enhydris subtaeniata): the biogeographic importance of dynamic river drainages and fluctuating sea levels for semiaquatic taxa in Indochina
Authors: Lukoschek Vimoksalehi , Osterhage Jennifer L. , Karns Daryl R. , Murphy John C. , Voris Harold K.
Published: September 2011

During the Cenozoic, Southeast Asia was profoundly affected by plate tectonic events, dynamic river systems, fluctuating sea levels, shifting coastlines, and climatic variation, which have influenced the ecological and evolutionary trajectories of the Southeast Asian flora and fauna. We examined the role of these paleogeographic factors on shaping phylogeographic patterns focusing on a species of semiaquatic snake, Enhydris subtaeniata (Serpentes: Homalopsidae) using sequence data from three mitochondrial fragments (cytochrome b, ND4, and ATPase—2785 bp). We sampled E. subtaeniata from seven locations in three river drainage basins that encompassed most of this species’ range. Genetic diversities were typically low within locations but high across locations. Moreover, each location had a unique suite of haplotypes not shared among locations, and pairwise φST values (0.713–0.998) were highly significant between all location pairs. Relationships among phylogroups were well resolved and analysis of molecular variance (AMOVA) revealed strong geographical partitioning of genetic variance among the three river drainage basins surveyed. The genetic differences observed among the populations of E. subtaeniata were likely shaped by the Quaternary landscapes of Indochina and the Sunda Shelf. Historically, the middle and lower Mekong consisted of strongly dissected river valleys separated by low mountain ranges and much of the Sunda Shelf consisted of lowland river valleys that served to connect faunas associated with major regional rivers. It is thus likely that the contemporary genetic patterns observed among populations of E. subtaeniata are the result of their histories in a complex terrain that created abundant opportunities for genetic isolation and divergence yet also provided lowland connections across now drowned river valleys.
High TCR diversity ensures optimal function andhomeostasis of Foxp3+ regulatory Tcells
Authors: Föhse Lisa , Suffner Janine , Suhre Karsten , Wahl Benjamin , Lindner Cornelia , Lee Chun‐Wei , Schmitz Susanne , Haas Jan D. , Lamprecht Stella , Koenecke Christian , Bleich André , Hämmerling Günter J. , Malissen Bernard , Suerbaum Sebastian , Förster Reinhold , Prinz Immo
Published: September 2011

Dominant tolerance to self‐antigen requires the presence of sufficient numbers of CD4+Foxp3+ Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen‐specific immuno‐regulation through Treg cells is not clear. Here, we developed and applied a novel high‐throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg‐cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non‐lymphopenic TCR‐transgenic recipients with low Treg‐cell diversity. In that system, we identified specific Treg‐cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class‐II‐presented self‐, food‐, or flora‐antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno‐regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self‐antigen shapes an organ‐optimized, yet highly diverse, local TCR repertoire.
Synthesis of Potassium (2R)‐2‐O‐α‐D‐Mannopyranosyl‐(1→2)‐α‐D‐glucopyranosyl‐2,3‐dihydroxypropanoate: A Naturally Compatible Solute
Authors: Lourenço Eva C. , Ventura M. Rita
Published: September 2011

An expedient synthesis of the potassium salt of (2R)‐2‐O‐α‐D‐mannopyranosyl‐(1→2)‐α‐D‐glucopyranosyl‐2,3‐dihydroxypropanoic acid (MGG)―a recently isolated, rare, compatible solute―was accomplished. A bis‐acetal‐protected thioglucoside, 6‐OTBDPS, with a 2‐OH group was used as the acceptor in the first glycosylation reaction with tetraacetylmannosyl trichloroacetimidate, and as the donor in the glycosylation reaction with the glycerate derivative. The α anomer was the only product of both glycosylation reactions, as expected for the formation of the α‐mannoside. The formation of the 1,2‐cis glucoside was more challenging.
A numerical investigation of the influence of the aspect ratio in three‐dimensional separated flows
Authors: Malamataris Nikolaos Athanasios
Published: September 2011

The influence of aspect ratio in three‐dimensional, numerical experiments of separated flows is studied in the case of the backward‐facing step at Reynolds numbers 600, 800, and 950. The computational domain is designed as an actual laboratory experiment. The governing equations are the steady state, isothermal, and incompressible Navier–Stokes equations. The expansion ratio of the computational domain is 1:2. The aspect ratio varies from 1:10 to 1:40. The results of the computations focus on the spanwise variations of the length and the strength of the two eddies along the lower and upper wall. It is concluded that both numerical and laboratory experiments should be designed with an aspect ratio of at least 1:20, if only the accuracy of the position of the detachment and the re‐attachment points matters. If the accuracy of the shear‐stress distributions is also taken into account, then an aspect ratio of at least 1:30 should be chosen. Finally, if the magnitudes of the vortex centers are also considered, then only the aspect ratio of 1:40 qualifies for a realization of two‐dimensional flow conditions in the plane of symmetry. This is contrary to the common practice in the field, at least from the side of laboratory experiments, where an aspect ratio of 1:10 is still considered adequate for this purpose. Copyright © 2011 John Wiley & Sons, Ltd.
The effects of connection reconstruction method on the interregional connectivity of brain networks via diffusion tractography
Authors: Li Longchuan , Rilling James K. , Preuss Todd M. , Glasser Matthew F. , Hu Xiaoping
Published: September 2011

Estimating the interregional structural connections of the brain via diffusion tractography is a complex procedure and the parameters chosen can affect the outcome of the connectivity matrix. Here, we investigated the influence of different connection reconstruction methods on brain connectivity networks. Specifically, we applied three connection reconstruction methods to the same set of diffusion MRI data, initiating tracking from deep white matter (method #1, M1), from the gray matter/white matter interface (M2), and from the gray/white matter interface with thresholded tract volume rather than the connection probability as the connectivity index (M3). Small‐world properties, hub identification, and hemispheric asymmetry in connectivity patterns were then calculated and compared across methods. Despite moderate to high correlations in the graph‐theoretic measures across different methods, significant differences were observed in small‐world indices, identified hubs, and hemispheric asymmetries, highlighting the importance of reconstruction method on network parameters. Consistent with the prior reports, the left precuneus was identified as a hub region in all three methods, suggesting it has a prominent role in brain networks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc
Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs
Authors: Borel Florie , Han Ruiqi , Visser Allerdien , Petry Harald , van Deventer Sander J.H. , Jansen Peter L.M. , Konstantinova Pavlina
Published: September 2011

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired HCC patient samples (16 untreated, 3 treated by chemotherapeutics). Twelve ABC transporters showed up-regulation in HCC compared with adjacent healthy liver. These include ABCA2, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, and ABCE1. The expression profile and function of some of these transporters have not been associated with HCC thus far. Because cellular microRNAs (miRNAs) are involved in posttranscriptional gene silencing, we hypothesized that regulation of ABC expression in HCC might be mediated by miRNAs. To study this, miRNAs were profiled and dysregulation of 90 miRNAs was shown in HCC compared with healthy liver, including up-regulation of 11 and down-regulation of 79. miRNA target sites in ABC genes were bioinformatically predicted and experimentally verified

in vitro

using luciferase reporter assays. In total, 13 cellular miRNAs were confirmed that target ABCA1, ABCC1, ABCC5, ABCC10, and ABCE1 genes and mediate changes in gene expression. Correlation analysis between ABC and miRNA expression in individual patients revealed an inverse relationship, providing an indication for miRNA regulation of ABC genes in HCC.

Conclusion :

Up-regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down-regulation. Up-regulation of five ABC genes appears to be mediated by 13 cellular miRNAs in HCC patient samples. miRNA-based gene therapy may be a novel and promising way to affect the ABC profile and overcome clinical multidrug resistance.
Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-Positive B-cell population
Authors: Doi Hiroyoshi , Iyer Tara K. , Carpenter Erica , Li Hong , Chang Kyong-Mi , Vonderheide Robert H. , Kaplan David E.
Published: September 2011

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anti–cluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4+ T-cell allostimulatory capacity. CD27+ memory B cells and, more specifically, CD27+IgM+ B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis.

Conclusion :

Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population.
Human resource executives' perceptions and measurement of the strategic impact of work/life initiatives
Authors: Morris Michael Lane , Heames Joyce Thompson , McMillan Heather S.
Published: September 2011

Given the stresses associated with today's demanding workplaces, work/life (w/l) initiatives continue to grow in importance as an organizational development (OD) intervention. In a period of increasing accountability, it is important for scholars and practitioners to demonstrate how OD interventions, like w/l initiatives, can be used as a strategic business tool to ameliorate the impact of stress in the workplace. To address this gap, the research questions for this study were based on the resource‐based view of the firm (Barney, 1991), while using the Organization Development Human Capital Accounting System (ODHCAS) model (Morris, Storberg‐Walker, & McMillan, 2009) as a basis for generating relevant metrics. This exploratory study used a survey instrument to compare senior human resource (HR) executives' perceptions of the strategic benefit of w/l initiatives in conjunction with their efforts to measure the impact of five types of w/l initiatives as they influence 16 measures representative of the elements of the ODHCAS. Findings from the study extend current research by revealing a relationship between HR executives' perceptions of the strategic impact of w/l initiatives and the decision to measure the impact of said initiatives.
Disseminated tumor cells in pancreatic cancer—an independent prognosticator of disease progression and survival
Authors: Effenberger Katharina E. , Schroeder Cornelia , Eulenburg Christine , Reeh Matthias , Tachezy Michael , Riethdorf Sabine , Vashist Yogesh K. , Izbicki Jakob R. , Pantel Klaus , Bockhorn Maximilian
Published: September 2011

Pancreatic cancer is one of the most devastating cancers with a 6‐month median survival and a 5‐year survival rate of 3–5%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of disseminated tumor cells (DTC) in bone marrow, a reservoir for early DTC potentially contributing to metastatic progression, of pancreatic cancer patients. After exclusion of patients with different postsurgery diagnosis or missing DTC status (n = 40) a total of 175 patients remained for final analyses. One‐hundred and nineteen patients were male and 96 female with a median age of 67 years, 96 patients underwent complete resection. Bone marrow aspirates taken at primary surgery were analyzed for DTC by an immunocytochemical cytokeratin assay and correlated to survival data. Overall 13.7% of patient samples (24/175) harbored DTC in their bone marrow. Histopathological parameters did not correlate significantly. Univariate survival analysis revealed a borderline significant correlation between DTC and decreased progression‐free survival (p = 0.069), and was significant for overall survival (p = 0.036). Regarding patients with resected tumors, the respective p‐values were 0.058 for progression‐free and 0.016 for overall survival. Importantly, the prognostic influence was independent from other risk factors as shown by multivariate analyses for progression‐free (p = 0.030, HR: 2.057; CI (95%): 1.073–3.943) and overall survival (p = 0.006, HR: 2.283; CI (95%): 1.260–4.135). The presence of DTC in bone marrow is a strong and independent prognostic factor of survival in patients with pancreatic cancer. Thus, bone‐targeting may be a new future therapeutic option for DTC‐positive patients.
Paget's disease in patients of Asian descent in New Zealand
Authors: Sankaran Shyam , Naot Dorit , Grey Andrew , Cundy Tim
Published: September 2011

Paget's disease is considered to be uncommon in Asian people, but we have noted a recent increase in the number of Asian patients referred to our clinic, on a background of an apparently decreasing prevalence in the population of European descent. In this article, we report clinical and epidemiological features of patients of Asian descent with Paget's disease, referred between 1973 and 2010 to the Auckland Paget's disease clinic. No Asian patients were referred before 1993, but 14 have presented between 1993 and 2010, with a median of 8 years between arrival into New Zealand and time of diagnosis. The patients were predominantly of south Asian origin. None of the 8 patients tested carried a mutation in exon 8 of the sequestosome 1 (SQSTM1) gene. The number of new Paget's disease referrals expressed as a proportion of the potentially at-risk Asian population in the Auckland region (derived from census data) was 1/104 in 2006 to 2011. Amongst Europeans, the corresponding value decreased from 10/104 in 1986 to 1991 to 2/104 in 2006 to 2010. The increased number of people of Asian descent diagnosed with Paget's disease in the Auckland region has paralleled the increasing size of the local Asian population. The continuing decline of Paget's disease in the European population, in conjunction with the emergence of the disease in the Asian population, supports the view that an environmental determinant to the disease exists and that Asians are not genetically protected. It also implies that the apparent reduction in Paget's disease prevalence in western cities is unlikely to be explicable by the rising Asian population of these cities. © 2012 American Society for Bone and Mineral Research
Unicuspid and bicuspid tooth crown formation in squamates
Authors: Handrigan Gregory R. , Richman Joy M.
Published: September 2011

The molecular and developmental factors that regulate tooth morphogenesis in nonmammalian species, such as snakes and lizards, have received relatively little attention compared to mammals. Here we describe the development of unicuspid and bicuspid teeth in squamate species. The simple, cone‐shaped tooth crown of the bearded dragon and ball python is established at cap stage and fixed in shape by the differentiation of cells and the secretion of dental matrices. Enamel production, as demonstrated by amelogenin expression, occurs relatively earlier in squamate teeth than in mouse molars. We suggest that the early differentiation in squamate unicuspid teeth at cap stage correlates with a more rudimentary tooth crown shape. The leopard gecko can form a bicuspid tooth crown despite the early onset of differentiation. Cusp formation in the gecko does not occur by the folding of the inner enamel epithelium, as in the mouse molar, but by the differential secretion of enamel. Ameloblasts forming the enamel epithelial bulge, a central swelling of cells in the inner enamel epithelium, secrete amelogenin at cap stage, but cease to do so by bell stage. Meanwhile, other ameloblasts in the inner enamel epithelium continue to secrete enamel, forming cusp tips on either side of the bulge. Bulge cells specifically express the gene Bmp2, which we suggest serves as a pro‐differentiation signal for cells of the gecko enamel organ. In this regard, the enamel epithelial bulge of the gecko may be more functionally analogous to the secondary enamel knot of mammals than the primary enamel knot. J. Exp. Zool. (Mol. Dev. Evol.) 316:598–608, 2011. © 2011 Wiley Periodicals, Inc.
Diffusion coefficient measurement using a temperature‐controlled fluid for quality control in multicenter studies
Authors: Chenevert Thomas L. , Galbán Craig J. , Ivancevic Marko K. , Rohrer Susan E. , Londy Frank J. , Kwee Thomas C. , Meyer Charles R. , Johnson Timothy D. , Rehemtulla Alnawaz , Ross Brian D.
Published: September 2011

Purpose:

To present the use of a quality control ice‐water phantom for diffusion‐weighted magnetic resonance imaging (DW‐MRI). DW‐MRI has emerged as an important cancer imaging biomarker candidate for diagnosis and early treatment response assessment. Validating imaging biomarkers through multicenter trials requires calibration and performance testing across sites.

Materials and Methods:

The phantom consisted of a center tube filled with distilled water surrounded by ice water. Following preparation of the phantom, ≈30 minutes was allowed to reach thermal equilibrium. DW‐MRI data were collected at seven institutions, 20 MRI scanners from three vendors, and two field strengths (1.5 and 3T). The phantom was also scanned on a single system on 16 different days over a 25‐day period. All data were transferred to a central processing site at the University of Michigan for analysis.

Results:

Results revealed that the variation of measured apparent diffusion coefficient (ADC) values between all systems tested was ±5%, indicating excellent agreement between systems. Reproducibility of a single system over a 25‐day period was also found to be within ±5% ADC values. Overall, the use of an ice‐water phantom for assessment of ADC was found to be a reasonable candidate for use in multicenter trials.

Conclusion:

The ice‐water phantom described here is a practical and universal approach to validate the accuracy of ADC measurements with ever changing MRI sequence and hardware design and can be readily implemented in multicenter clinical trial designs. J. Magn. Reson. Imaging 2011. © 2011 Wiley‐Liss, Inc.
Is administration of gadolinium‐based contrast media to pregnant women and small children justified?
Authors: Sundgren Pia C. , Leander Peter
Published: September 2011

The use of gadolinium‐based contrast media in pregnant or lactating women has been discouraged at many radiology departments due to the lack of knowledge of the risks for the fetus and the unwillingness to expose neonates to unnecessary drugs. In the present review the current literature and present guidelines regarding the use of gadolinium‐based contrast media have been reviewed to validate the justification for their administration to pregnant or lactating women and small children. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Mapping system for coregistration of cardiac mri and ex vivo tissue sampling
Authors: Young Alistair A. , Crossman David J. , Ruygrok Peter N. , Cannell Mark B.
Published: September 2011

Purpose:

To design a method suitable for obtaining tissue samples from regions of different function as ascertained by magnetic resonance imaging (MRI).

Materials and Methods:

In vivo MRI was used to create azimuthal projections of the heart from dilated cardiomyopathy transplant patients with the cardiac valves in the center and four concentric rings representing the septum and free wall. Tagged MRI could identify regions of different contractile strength that were then transferred onto the map projection. The resulting tissue sampling map was used to guide dissection of tissue samples from the explanted heart for analysis by electron microscopy (EM) as well as provide samples for subsequent mRNA analysis. Accuracy of the sampling was determined in a sheep heart using 17 fiduciary markers glued to the epicardial surface.

Results:

Tagged MRI identified areas of “normal” (%Sc −11), “poor” (%Sc −4) and “failed” contraction (%Sc +3). The mapping method we developed enabled straightforward sampling of these regions after surgical excision. EM showed good tissue preservation while the test of accuracy using the fiduciary markers showed a sampling accuracy of 0.3 ± 3.7 mm. This was similar to the resolution of tagged MRI images themselves.

Conclusion:

The methods we have developed can accurately guide tissue sampling for ex vivo tissue analysis. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
Accelerating cine‐MR imaging in mouse hearts using compressed sensing
Authors: Wech Tobias , Lemke Angela , Medway Debra , Stork Lee‐Anne , Lygate Craig A. , Neubauer Stefan , Köstler Herbert , Schneider Jürgen E.
Published: September 2011

Purpose:

To combine global cardiac function imaging with compressed sensing (CS) in order to reduce scan time and to validate this technique in normal mouse hearts and in a murine model of chronic myocardial infarction.

Materials and Methods:

To determine the maximally achievable acceleration factor, fully acquired cine data, obtained in sham and chronically infarcted (MI) mouse hearts were 2–4‐fold undersampled retrospectively, followed by CS reconstruction and blinded image segmentation. Subsequently, dedicated CS sampling schemes were implemented at a preclinical 9.4 T magnetic resonance imaging (MRI) system, and 2‐ and 3‐fold undersampled cine data were acquired in normal mouse hearts with high temporal and spatial resolution.

Results:

The retrospective analysis demonstrated that an undersampling factor of three is feasible without impairing accuracy of cardiac functional parameters. Dedicated CS sampling schemes applied prospectively to normal mouse hearts yielded comparable left‐ventricular functional parameters, and intra‐ and interobserver variability between fully and 3‐fold undersampled data.

Conclusion:

This study introduces and validates an alternative means to speed up experimental cine‐MRI without the need for expensive hardware. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
The presence of two local myocardial sheet populations confirmed by diffusion tensor MRI and histological validation
Authors: Kung Geoffrey L. , Nguyen Tom C. , Itoh Aki , Skare Stefan , Ingels Neil B. , Miller D. Craig , Ennis Daniel B.
Published: September 2011

Purpose:

To establish the correspondence between the two histologically observable and diffusion tensor MRI (DTMRI) measurements of myolaminae orientation for the first time and show that single myolaminar orientations observed in local histology may result from histological artifact.

Materials and Methods:

DTMRI was performed on six sheep left ventricles (LV), then corresponding direct histological transmural measurements were made within the anterobasal and lateral‐equatorial LV. Secondary and tertiary eigenvectors of the diffusion tensor were compared with each of the two locally observable sheet orientations from histology. Diffusion tensor invariants were calculated to compare differences in microstructural diffusive properties between histological locations with one observable sheet population and two observable sheet populations.

Results:

Mean difference ± 1SD between DTMRI and histology measured sheet angles was 8° ± 27°. Diffusion tensor invariants showed no significant differences between histological locations with one observable sheet population and locations with two observable sheet populations.

Conclusion:

DTMRI measurements of myolaminae orientations derived from the secondary and tertiary eigenvectors correspond to each of the two local myolaminae orientations observed in histology. Two local sheet populations may exist throughout LV myocardium, and one local sheet population observed in histology may be a result of preparation artifact. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
Electrical stimulation promotes the survival of oligodendrocytes in mixed cortical cultures
Authors: Gary Devin S. , Malone Misti , Capestany Paul , Houdayer Thierry , McDonald John W.
Published: September 2011

Oligodendrocyte (OLG) death plays a major role in white matter dysfunction and demyelination following injury to the CNS. Axonal contact, communication, and neuronal activity appear to promote OLG survival and function in cell culture and during development. The application of electrical stimulation to mixed neural cultures has been shown to promote OLG differentiation and the formation of myelin in vitro. Here we show that OLG viability can be significantly enhanced in mixed cortical cultures by applying biphasic pulses of electrical stimulation (ESTIM). Enhanced survival via ESTIM requires the presence of neurons and is suppressed by inhibition of voltage‐gated sodium channels. Additionally, contact between the axon and OLG is necessary for ESTIM to promote OLG survival. This report suggests that patterned neuronal activity could repress delayed progression of white matter injury and promote CNS repair in neurological conditions that involve white matter damage. Journal of Neuroscience Research (2011) © 2011 Wiley Periodicals, Inc.
Inhibitory effect of NAP‐22 on the phosphatase activity of synaptojanin‐1
Authors: Takaichi Rika , Odagaki Sin‐Ichi , Kumanogoh Haruko , Nakamura Shun , Morita Mitsuhiro , Maekawa Shohei
Published: September 2011

Endocytosis of the synaptic vesicle is a complicated process, in which many proteins and lipids participate. Phosphatidylinositol 4,5‐bisphosphate (PIP2) plays important roles in the process, and the dynamic regulation of this lipid is one of the key events. Synaptojanin is a PIP2 phosphatase, and dephosphorylation of PIP2 of the clathrin coated‐vesicle results in the uncoating of the vesicle. NAP‐22 is one of the major proteins of the neuronal detergent‐resistant membrane microdomain and localizes in both the presynaptic plasma membrane and the synaptic vesicle. To elucidate the role of NAP‐22 in synaptic function, a screening of the NAP‐22 binding proteins through pull‐down assay was performed. In addition to CapZ protein, synaptojanin‐1 was detected by LC‐MS/MS, and Western blotting using antisynaptojanin‐1 confirmed this result. The interaction seems to be important in the course of synaptic vesicle endocytosis, because NAP‐22 inhibited the phosphatase activity of synaptojanin in a dose‐dependent manner. The inhibitory region for 5‐phosphatase and the binding region for PIP2 overlapped in the amino acid sequence of NAP‐22, so elucidation of the regulatory mechanism of the PIP2 binding ability of NAP‐22 could be important in understanding the membrane dynamics at the presynaptic region. © 2011 Wiley Periodicals, Inc.
Neutral sphingomyelinase activation precedes NADPH oxidase‐dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor‐α
Authors: Barth Brian M. , Gustafson Sally J. , Kuhn Thomas B.
Published: September 2011

Inflammation accompanied by severe oxidative stress plays a vital role in the orchestration and progression of neurodegeneration prevalent in chronic and acute central nervous system pathologies as well as in aging. The proinflammatory cytokine tumor necrosis factor‐α (TNFα) elicits the formation of the bioactive ceramide by stimulating the hydrolysis of the membrane lipid sphingomyelin by sphingomyelinase activities. Ceramide stimulates the formation of reactive oxygen species (ROS) and apoptotic mechanisms in both neurons and nonneuronal cells, establishing a link between sphingolipid metabolism and oxidative stress. We demonstrated in SH‐SY5Y human neuroblastoma cells and primary cortical neurons that TNFα is a potent stimulator of Mg2+‐dependent neutral sphingomyelinase (Mg2+‐nSMase) activity, and sphingomyelin hydrolysis, rather than de novo synthesis, was the predominant source of ceramide increases. Mg2+‐nSMase activity preceded an accumulation of ROS by a neuronal NADPH oxidase (NOX). Notably, TNFα provoked an NOX‐dependent oxidative damage to sphingosine kinase‐1, which generates sphingosine‐1‐phosphate, a ceramide metabolite associated with neurite outgrowth. Indeed, ceramide and ROS inhibited neurite outgrowth of dorsal root ganglion neurons by disrupting growth cone motility. Blunting ceramide and ROS formation both rescued sphingosine kinase‐1 activity and neurite outgrowth. Our studies suggest that TNFα‐mediated activation of Mg2+‐nSMase and NOX in neuronal cells not only produced the neurotoxic intermediates ceramide and ROS but also directly antagonized neuronal survival mechanisms, thus accelerating neurodegeneration. Journal of Neuroscience Research (2011) © 2011 Wiley Periodicals, Inc.
Differential expression of sprouty genes in hepatocellular carcinoma
Authors: Sirivatanauksorn Yongyut , Sirivatanauksorn Vorapan , Srisawat Chatchawan , Khongmanee Amnart , Tongkham Chalita
Published: September 2011

Background and Objectives

Sprouty (Spry) proteins are important modulators of the RTK/Ras/MAPK pathway, overactivation of which is associated with hepatocellular carcinoma (HCC). Thus far, the roles of Sprouty in HCC is still unclear.

Methods

The expressions of SPRY1, SPRY2, SPRY3, and SPRY4, at the mRNA levels were determined by quantitative RT‐PCR in paired HCC and non‐tumor liver tissues from 31 patients.

Results

The expression levels of SPRY1, SPRY2, and SPRY4 in tumor tissues were significantly different from those in non‐tumor tissues with the average log fold change values of 0.15, −0.34, and −0.37, respectively; however, that of SPRY3 was not significantly different. SPRY1 expression was also found to be significantly up‐regulated in the cases without underlying cirrhosis compared with those with cirrhosis (log fold change of 0.35 and −0.02, respectively, P < 0.05), whereas SPRY2 expression was significantly lower in the cases with advanced HCC (log fold change of −0.12 and −0.52 in early and advanced stages, respectively, P < 0.05) and in those with angiolymphatic invasion (log fold change of −0.47 and −0.16 in the presence and absence thereof, P < 0.05).

Conclusion

This study demonstrates that Sprouty genes are differentially expressed in HCC and might provide some insight into their roles in HCC carcinogenesis. J. Surg. Oncol. 2012; 105:273–276. © 2011 Wiley Periodicals, Inc.
Excellent Posttransplant Survival for Patients with Nonalcoholic Steatohepatitis in the United States
Authors: Afzali Anita , Berry Kristin , Ioannou George N.
Published: September 2011

Because of the ongoing epidemics of obesity and diabetes, nonalcoholic steatohepatitis (NASH) may become a leading indication for liver transplantation. There are concerns about the posttransplant survival of patients with NASH because of associated cardiovascular and metabolic risk factors. We aimed to determine recent trends in the proportion of patients undergoing transplantation for NASH-related cirrhosis in the United States and to estimate their posttransplant survival. We used data provided by the United Network for Organ Sharing for first-time adult cadaveric liver transplants performed in the United States between January 1, 1997 and October 31, 2010 (n = 53,738). The proportion of liver transplants performed for NASH-related cirrhosis increased dramatically from 1.2% in 1997-2003 to 7.4% in 2010 when NASH was the fourth most common indication for transplantation. The posttransplant survival of patients with NASH (n = 1810) at 1 (87.6%), 3 (82.2%), and 5 years (76.7%) was superior to the survival of patients with hepatocellular carcinoma, hepatitis C virus, alcoholic liver disease, acute hepatic necrosis, hemochromatosis, or cryptogenic liver disease and was inferior to the survival of only 4 groups of patients (those with primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or hepatitis B virus). In conclusion, NASH-related cirrhosis is increasing rapidly as an indication for liver transplantation in the United States and is associated with excellent posttransplant survival.
Left Lobe Adult-to-Adult Living Donor Liver Transplantation: Should Portal Inflow Modulation Be Added?
Authors: Ishizaki Yoichi , Kawasaki Seiji , Sugo Hiroyuki , Yoshimoto Jiro , Fujiwara Noriko , Imamura Hiroshi
Published: September 2011

Recently, the successful application of portal inflow modulation has led to renewed interest in the use of left lobe grafts in adult-to-adult living donor liver transplantation (LDLT). However, data on the hepatic hemodynamics supporting portal inflow modulation are limited, and the optimal portal circulation for a liver graft is still unclear. We analyzed 42 consecutive adult-to-adult left lobe LDLT cases without splenectomy or a portocaval shunt. The mean actual graft volume (GV)/recipient standard liver volume (SLV) ratio was 39.8% ± 5.7% (median = 38.9%, range = 26.1%-54.0%). The actual GV/SLV ratio was less than 40% in 24 of the 42 cases, and the actual graft-to-recipient weight ratio was less than 0.8% in 17 of the 42 recipients. The mean portal vein pressure (PVP) was 23.9 ± 7.6 mm Hg (median = 23.5 mm Hg, range = 9-38 mm Hg) before transplantation and 21.5 ± 3.6 mm Hg (median = 22 mm Hg, range = 14-27 mm Hg) after graft implantation. The mean portal pressure gradient (PVP − central venous pressure) was 14.5 ± 6.8 mm Hg (median = 13.5 mm Hg, range = 3-26 mm Hg) before transplantation and 12.4 ± 4.4 mm Hg (median = 13 mm Hg, range = 1-21 mm Hg) after graft implantation. The mean posttransplant portal vein flow was 301 ± 167 mL/minute/100 g of liver in the 38 recipients for whom it was measured. None of the recipients developed small-for-size syndrome, and all were discharged from the hospital despite portal hyperperfusion. The overall 1-, 3-, and 5-year patient and graft survival rates were 100%, 97%, and 91%, respectively. In conclusion, LDLT with a left liver graft without splenectomy or a portocaval shunt yields good long-term results for adult patients with a minimal donor burden.
Liver Transpl 18:305–314, 2012.
© 2012 AASLD.
An Electrospun Degradable Scaffold Based on a Novel Hydrophilic Polyester for Tissue‐Engineering Applications
Authors: Seyednejad Hajar , Ji Wei , Schuurman Wouter , Dhert Wouter J. A. , Malda Jos , Yang Fang , Jansen John A. , van Nostrum Cornelus , Vermonden Tina , Hennink Wim E.
Published: September 2011

Scaffolds based on a novel functionalized polyester, pHMGCL, are electrospun and characterized morphologically and physically. In vitro degradation studies of pHMGCL films show considerable mass loss and molecular weight reduction within 70 weeks. Scaffolds composed of fibers with uniform diameter (≈ 900 nm) and with melting temperatures higher than body temperature are prepared. As an indication for the feasibility of this material for regenerative medicine approaches, articular chondrocytes are seeded onto electrospun pHMGCL scaffolds. Chondrocytes attach to the fibers and re‐differentiate as demonstrated by the production of GAG and collagen type II within four weeks of in vitro culture. Hydrophilic pHMGCL scaffolds may thus be useful for tissue engineering applications.

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Structure and Mechanical Properties of an Injection‐Molded Thermoplastic Polyurethane as a Function of Melt Temperature
Authors: Stribeck Norbert , Zeinolebadi Ahmad , Sari Morteza Ganjaee , Frick Achim , Mikoszek Marzena , Botta Stephan
Published: September 2011

Thermoplastic polyurethanes (TPUs) molded at 205, 215, and 235 °C are monitored by SAXS and WAXS during straining. A non‐affine nanostructure deformation and related evolution mechanisms are found. DSC and microscopy are applied. DSC shows two melting endotherms. The results indicate that melts kept below the second peak stay phase‐separated. The orientation parameter f(ϵ) and df/dϵ from WAXS are related to chain orientation mechanisms (strain ϵ). SAXS shows hard domains that are only correlated to a next neighbor (“sandwich”). Thick sandwiches lengthen more than thin ones. Thin‐layer sandwiches feature a strain limit. Some are converted into thick‐layer sandwiches. Two materials have tough hard domains. Material processed at 235 °C is soft and contains weak hard domains that fail for ϵ > 0.75.
Mechanical Performance of Soy‐Hull‐Reinforced Bioplastic Green Composites: A Comparison with Polypropylene Composites
Authors: Nanda Malaya R. , Misra Manjusri , Mohanty Amar K.
Published: September 2011

A blend composition of poly(3‐hydroxybutyrate‐co‐valerate) and polylactide is used as a bioplastic matrix and reinforced with soy hull to engineer novel green composites. A comparative study with soy‐hull‐reinforced polypropylene composite system is performed. A compatibilizer is used to engineer the novel class of green composites with a balanced stiffness and toughness performance with the target to substitute PP‐based composites. The flexural and impact strength along with hydrophobicity of compatibilized composites are improved significantly over the noncompatibilized counterpart. The fiber/matrix interaction is investigated by SEM. These green composites have the potential to substitute PP‐based composites in some applications.

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Applying the Traditional Solution Melt Polymerization for the in situ Intercalation of Polyamide 6.6‐Clay Nanocomposites
Authors: Boussia Anastasia C. , Vouyiouka Stamatina N. , Papaspyrides Constantine D.
Published: September 2011

The traditional PA 6.6 production route, i.e. solution melt polymerization followed by extrusion, is applied to the in situ intercalation of PA 6.6/clay nanocomposites. Organoclays of different types are tested and the derived nanocomposites are thoroughly characterized in terms of molecular weight, thermal properties and morphology. Reaction acceleration is found in the presence of fully exchanged organoclays, which is attributed to a chain extension mechanism based on clay SiOH groups. Analysis of the nanocomposites' nanostructure indicates that the applied solution melt polymerization process results in some flocculation of the tested organoclays, which is improved in some cases after extrusion and leads to partially exfoliated nanocomposites.

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Novel Biodegradable Block Copolymers of Poly(ethylene glycol) (PEG) and Cationic Polycarbonate: Effects of PEG Configuration on Gene Delivery
Authors: Yang Chuan , Ong Zhan Yuin , Yang Yi‐Yan , Ee Pui Lai Rachel , Hedrick James L.
Published: September 2011

A novel amine‐functionalized polycarbonate was synthesized and its excellent gene transfection ability in vitro is demonstrated. In the framework of adapting the cationic polycarbonate for in vivo gene delivery applications, here the design and synthesis of biodegradable block copolymers of poly(ethylene glycol) (PEG) and amine‐functionalized polycarbonate with a well‐defined molecular architecture and molecular weight is achieved by metal‐free organocatalytic ring‐opening polymerization. Copolymers in triblock cationic polycarbonate‐block‐PEG‐block‐cationic polycarbonate and diblock PEG‐block‐cationic polycarbonate configurations, in comparison with a non‐PEGylated cationic polycarbonate control, are investigated for their influence on key aspects of gene delivery. Among the polymers with similar molecular weights and N content, the triblock copolymer exhibit more favorable physicochemical (i.e., DNA binding, size, zeta‐potential, and in vitro stability) and biological (i.e., cellular uptake and luciferase reporter gene expression) properties. Importantly, the various cationic polycarbonate/DNA complexes are biocompatible, inducing minimal cytotoxicities and hemolysis. These results suggest that the triblock copolymer is a more useful architecture in future cationic polymer designs for successful systemic therapeutic applications.
Feeding the Foxes: An Experimental Study to Assess Their Taphonomic Signature on Leporid Remains
Authors: Lloveras L. , Moreno‐García M. , Nadal J.
Published: September 2011

The red fox (Vulpes vulpes) is a generalist predator, but in areas where the abundance of rabbits is high, they constitute one of the most common prey species. Taphonomic studies on leporid remains consumed by this terrestrial carnivore are scarce, and its role as an agent responsible for bone accumulations in the fossil record is not fully understood. With the aim of contributing new data to this subject, an experimental study was carried out with four red foxes kept in captivity. They were fed with complete rabbit carcasses. Scats and non‐ingested remains were recovered in order to analyse anatomical representation, breakage and digestion patterns. Results were compared with another sample derived exclusively from wild red foxes' scats. Variability occurs among the three samples, suggesting that the identification of the taphonomic signature of this predator on archaeological assemblages of leporid remains is not a straightforward matter. Copyright © 2011 John Wiley & Sons, Ltd.
Dose‐dependent proteomic analysis of glioblastoma cancer stem cells upon treatment with γ‐secretase inhibitor
Authors: Dai Lan , He Jintang , Liu Yashu , Byun Jaeman , Vivekanandan Anuradha , Pennathur Subramaniam , Fan Xing , Lubman David M.
Published: September 2011

Notch signaling has been demonstrated to have a central role in glioblastoma (GBM) cancer stem cells (CSCs) and we have demonstrated recently that Notch pathway blockade by γ‐secretase inhibitor (GSI) depletes GBM CSCs and prevents tumor propagation both in vitro and in vivo. In order to understand the proteome alterations involved in this transformation, a dose‐dependent quantitative mass spectrometry (MS)‐based proteomic study has been performed based on the global proteome profiling and a target verification phase where both Immunoassay and a multiple reaction monitoring (MRM) assay are employed. The selection of putative protein candidates for confirmation poses a challenge due to the large number of identifications from the discovery phase. A multilevel filtering strategy together with literature mining is adopted to transmit the most confident candidates along the pipeline. Our results indicate that treating GBM CSCs with GSI induces a phenotype transformation towards non‐tumorigenic cells with decreased proliferation and increased differentiation, as well as elevated apoptosis. Suppressed glucose metabolism and attenuated NFR2‐mediated oxidative stress response are also suggested from our data, possibly due to their crosstalk with Notch Signaling. Overall, this quantitative proteomic‐based dose‐dependent work complements our current understanding of the altered signaling events occurring upon the treatment of GSI in GBM CSCs.
The psychosocial impact of stigma in people with head and neck or lung cancer
Authors: Lebel Sophie , Castonguay Myriam , Mackness Gudrun , Irish Jonathan , Bezjak Andrea , Devins Gerald M.
Published: September 2011

Background

Lung and head and neck cancers are widely believed to produce psychologically destructive stigma because they are linked to avoidable risk‐producing behaviors and are highly visible, but little research has tested these ideas. We examined cancer‐related stigma, its determinants, and its psychosocial impact in lung (n = 107) and head and neck cancer survivors (n = 99) ≤3 years post‐diagnosis. We investigated cancer site, self‐blame, disfigurement, and sex as determinants, benefit finding as a moderator, and illness intrusiveness as a mediator of the relation between stigma and its psychosocial impact.

Methods

Prospective participants received questionnaire packages 2 weeks before scheduled follow‐up appointments. They self‐administered widely used measures of subjective well‐being, distress, stigma, self‐blame, disfigurement, illness intrusiveness, and post‐traumatic growth.

Results

As hypothesized, stigma correlated significantly and uniquely with negative psychosocial impact, but contrary to common beliefs, reported stigma was comparatively low. Reported stigma was higher in (i) men than women, (ii) lung as compared with head and neck cancer, and (iii) people who were highly disfigured by cancer and/or its treatment. Benefit finding buffered stigma's deleterious effects, and illness intrusiveness was a partial mediator of its psychosocial impact.

Conclusions

Stigma exerts a powerful, deleterious psychosocial impact in lung and head and neck cancers, but is less common than believed. Patients should be encouraged to remain involved in valued activities and roles and to use benefit finding to limit its negative effects. Copyright © 2011 John Wiley & Sons, Ltd.
Effects of junctions on carbon nanotube network‐based devices
Authors: Kang Pil Soo , Kim Gyu Tae
Published: September 2011

Realistic random networks of carbon nanotubes (CNTs) were simulated by the noble hybrid method combining Monte Carlo and SPICE simulations. Near the percolation threshold, the electrical characteristics of networks are strongly affected by the contacts among nanotubes. The nonlinear electrical junctions in the CNT network were modeled by suitable SPICE models and simulated using our hybrid simulation method. We successfully described the morphological percolation threshold, and the critical density was determined as a function of normalized length. The effects of electrical junctions on the scaling of the sheet conductance were investigated.