bluuebunny/crossref_metadata_2025 huggingface dataset:
High throughput analysis of proteins associating with a proinvasive MT1‐MMP in human malignant melanoma A375 cells
Authors: Tomari Taizo , Koshikawa Naohiko , Uematsu Takayuki , Shinkawa Takashi , Hoshino Daisuke , Egawa Nagayasu , Isobe Toshiaki , Seiki Motoharu
Published: March 2009

Membrane‐type 1 matrix metalloproteinase (MT1‐MMP), a powerful modulator of the pericellular environment, promotes migration, invasion, and proliferation of cells. To perform its potent proteolytic activity in a controlled manner, MT1‐MMP has to be regulated precisely. However, our knowledge about substrates and regulatory proteins is still very limited. In this study we identify a catalog of proteins that directly or indirectly interact with MT1‐MMP. We expressed a FLAG‐tagged MT1‐MMP stably in human malignant melanoma A375 cells. We prepared cell lysate using Brij98 and MT1‐MMP was affinity purified together with associating proteins using an anti‐FLAG antibody. A distinct set of membrane proteins was found to copurify with MT1‐MMP when biotin‐labeled proteins were monitored. The proteins were analyzed with an integrated system composed of nano‐flow liquid chromatography and tandem mass spectrometry. We identified 158 proteins including several previously reported to bind MT1‐MMP, although most had not previously been identified. Six of these membrane proteins, including one previously shown to interact with MT1‐MMP, were co‐expressed with MT1‐MMP in HT1080 cells. Five of the latter were found to associate with MT1‐MMP in an immunoprecipitation assay. Immunostaining of cells expressing each of these test proteins revealed that one colocalized with MT1‐MMP at the ruffling membrane and the other at the perinuclear vesicles. In contrast, another protein which did not coprecipitate with MT1‐MMP showed no colocalization. Recombinant MT1‐MMP cleaved two of the tested proteins at least in vitro. Thus, we provide a valuable resource to identify substrates and regulators of MT1‐MMP in tumor cells. (Cancer Sci 2009; 100: 1284–1290)
A frameshift mutation in the coding region of the myostatin gene (MSTN) affects carcass conformation and fatness in Norwegian White Sheep (Ovis aries)
Authors: Boman I. A. , Klemetsdal G. , Blichfeldt T. , Nafstad O. , Våge D. I.
Published: March 2009

Mutations in the coding region of the myostatin gene (MSTN) are known to cause an increased muscle mass (IMM) phenotype in several mammals, including mice, dogs, cattle and humans. In sheep, a mutation in the 3′‐UTR region introducing a microRNA target site has been reported to cause an IMM‐like phenotype because of downregulation of translation. Here we report a novel single base deletion in the coding region of the myostatin gene causing an IMM phenotype in Norwegian White Sheep, characterized by a high carcass conformation class and low fat class (EUROP classification system). The deletion disrupts the reading frame from amino acid (aa) position 320, ending in a premature stop codon in aa position 359. In our material, these MSTN mutations segregated in a pattern showing that they reside in two different haplotypes. The phenotypic effect of the single base deletion is more profound than that of the 3′‐UTR mutation.
Colonic stem cell data are consistent with the immortal model of stem cell division under non‐random strand segregation
Authors: Walters K.
Published: March 2009

Objectives:  Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the ‘immortal strand hypothesis’, and explore the effect on conclusions of previously published results.

Materials and methods:  For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non‐random strand segregation and compare them with those observed.

Results:  The calculated mean and variance are consistent with an immortal model that incorporates non‐random strand segregation for a range of stem cell numbers and levels of preferential strand segregation.

Conclusions:  Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.
Over‐expression of a Populus peroxisomal ascorbate peroxidase (PpAPX) gene in tobacco plants enhances stress tolerance
Authors: Li Y‐J. , Hai R‐L. , Du X‐H. , Jiang X‐N. , Lu H.
Published: March 2009

Ascorbate peroxidase (APX) plays an important role in the metabolism of hydrogen peroxide in higher plants. We studied the effect of over‐expressing a Populus peroxisomal ascorbate peroxidase (PpAPX) gene under the control of the cauliflower mosaic virus 35S promoter or the rd29 promoter in transgenic tobacco. High levels of PpAPX gene expression were observed in 35S‐PpAPX transgenic plants, with a 50% increase in APX activity. The constitutive expression of PpAPX in the tobacco exhibited no morphological abnormalities, while significantly increased root growth was observed in transgenic plants, when compared to control plants. Several independently transformed lines were propagated and evaluated for resistance to methyl viologen (MV), drought and salt stress. Visual assessment of transgenic and control lines exposed to MV (50 or 100 μmol) confirmed that over‐expression of APX minimized leaf damage. APX activity was nearly 80% higher in the leaves of transgenic plants in response to drought or salt stresses. Moreover, the transgenic tobacco also showed significantly improved drought resistance and salt tolerance at the vegetative stage. RNA blot analysis indicated that the PpAPX transcript level was very low under normal growing conditions in rd29Ap‐PpAPX plants, but clearly increased under drought stress. Our results show that PpAPX does not play a significant role under normal growing conditions, but did ameliorate oxidative injury under abiotic stress. The Ad29 promoter should be used as an inducible promoter in transgenic works.
Prokaryotic extracellular enzymatic activity in relation to biomass production and respiration in the meso‐ and bathypelagic waters of the (sub)tropical Atlantic
Authors: Baltar Federico , Arístegui Javier , Sintes Eva , Van Aken Hendrik M. , Gasol Josep M. , Herndl Gerhard J.
Published: March 2009

Prokaryotic extracellular enzymatic activity, abundance, heterotrophic production and respiration were determined in the meso‐ and bathypelagic (sub)tropical North Atlantic. While prokaryotic heterotrophic production (PHP) decreased from the lower euphotic layer to the bathypelagic waters by two orders of magnitude, prokaryotic abundance and cell‐specific PHP decreased only by one order of magnitude. In contrast to cell‐specific PHP, cell‐specific extracellular enzymatic activity (alpha‐ and beta‐glucosidase, leucine aminopeptidase, alkaline phosphatase) increased with depth as did cell‐specific respiration rates. Cell‐specific alkaline phosphatase activity increased from the intermediate water masses to the deep waters up to fivefold. Phosphate concentrations, however, varied only by a factor of two between the different water masses, indicating that phosphatase activity is not related to phosphate availability in the deep waters. Generally, cell‐specific extracellular enzymatic activities were inversely related to cell‐specific prokaryotic leucine incorporation. Thus, it is apparent that the utilization of deep ocean organic matter is linked to higher cell‐specific extracellular enzymatic activity and respiration and lower cell‐specific PHP than in surface waters.
The prevalence of metabolic syndrome in Danish patients with HIV infection: the effect of antiretroviral therapy
Authors: Hansen BR , Petersen J , Haugaard SB , Madsbad S , Obel N , Suzuki Y , Andersen O
Published: March 2009

Objectives

The prevalence of metabolic syndrome (MS) in HIV‐infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV‐infected patients and estimated the effect of the various classes of antiretroviral therapies on the prevalence of MS and its components.

Methods

A cross‐sectional study was performed in which data were obtained from fasting blood tests, anthropometry, an interview questionnaire and whole‐body dual‐energy X‐ray absorptiometry (DEXA) scans. MS was defined using the National Cholesterol Education Programme (NCEP) Adult Treatment Panel (ATP) III diagnostic criteria.

Results

Five hundred and sixty‐six patients were included in the study, of whom 27% were diagnosed with MS. In univariate analysis, the duration of treatment with different drug classes was associated with the prevalence of MS. In multivariate analysis, no association was demonstrated between therapeutic duration or modality and the occurrence of MS. Current nonthymidine reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) therapies were both associated with increased plasma triglycerides (TG) [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.73–6.74; and OR 1.96, 95% CI 1.19–3.22, respectively].

Conclusions

MS is prevalent in HIV‐infected Danes. However, treatment with specific drug classes does not seem to confer an elevated risk for MS, other than the risk conferred by known acute effects on triglycerides.
Primary drug resistance and transmission analysis of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore
Authors: Lee CC , Sun YJ , Barkham T , Leo YS
Published: March 2009

Objectives

The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.

Methods

Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.

Results

Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.

Conclusions

In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.
Effects of HIV status and antiretroviral therapy on blood pressure
Authors: Wilson SL , Scullard G , Fidler SJ , Weber JN , Poulter NR
Published: March 2009

Objective

High blood pressure is a major risk factor for cardiovascular disease and concerns have been raised over its possible association with antiretroviral drugs. The objective of this study was to explore the associations among blood pressure, HIV status and two predefined highly active antiretroviral therapy (HAART) regimens: treatment with and without nonnucleoside reverse transcriptase inhibitors (NNRTIs) (NNRTI‐ and non‐NNRTI‐based HAART).

Method

A cross‐sectional survey was conducted among 612 adults attending the Sexual Health Outpatient Department at St Mary's NHS Hospital Trust, London.

Results

HIV‐infected patients treated with NNRTIs had a blood pressure that was 4.6/4.2 mmHg higher than those who were HIV positive but treatment naïve. The diastolic difference remained statistically significant after adjusting for potential confounders of this association (2.4 mmHg; P=0.03). There was no difference in blood pressure between those treated with non‐NNRTI‐based regimens and those who were HIV positive but treatment naïve.

Conclusion

NNRTIs may be associated with an increase in blood pressure. Pending further more robust evidence from randomized clinical trials it would be prudent for clinicians to monitor blood pressure in all HIV‐infected patients, particularly after initiating treatment with NNRTIs, and to commence antihypertensive therapy whenever appropriate.
Subclinical rhythmic electrographic discharge of adults (SREDA) in a case with spinocerebellar degeneration improved clinically by thyrotropin‐releasing hormone
Authors: FUKUTA Mayuko , KIRINO Eiji , INOUE Reiichi , ARAI Heii
Published: March 2009

Herein, we report on a patient with spinocerebellar degeneration who exhibited subclinical rhythmic electrographic discharge of adults (SREDA). Thyrotropin‐releasing hormone (TRH) improved the clinical symptoms and SREDA was observed only when administration of thyrotropin‐releasing hormone was discontinued and the symptoms worsened. Furthermore, after resuming administration of taltirelin hydrate, a TRH analog, the improvement in motor function was accompanied by a decrease in delirium. It is plausible that taltirelin hydrate improved the distorted cerebral blood flow, which has been reported previously as the mechanism underlying SREDA, as a consequence of the functional improvement in neurotransmitter systems.
Investigation of the short‐ and long‐term effects of donepezil on cognitive function in Alzheimer's disease
Authors: INOUE Jun , HOSHINO Ryoichi , NOJIMA Hidenori , OKAMOTO Norio
Published: March 2009

Background:  Donepezil is effective in maintaining cognitive function in patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the short‐ and long‐term effects of donepezil on cognitive function after 2 years treatment.

Methods:  The present retrospective study was performed on 122 AD outpatients who had been taking donepezil for ≥1 year. All subjects underwent periodic examination of cognitive function (Mini‐Mental State Examination (MMSE), Rorschach Cognitive Index (RCI)) and clinical evaluation on the Clinical Dementia Rating (CDR); first before starting treatment and then at 4‐month intervals after initiation of donepezil. Patients were divided into three groups: (i) MG, the ‘maintained’ group, in which the global CDR score was maintained during treatment; (ii) DeG, the ‘declined’ group, in which the global CDR score increased; and (iii) DrG, the drop out group, who discontinued the treatment. Changes in scores on the MMSE and RCI were compared before treatment and at 4‐month intervals within each group. In addition, over each 4‐month period, MMSE and RCI scores were compared between the three groups. Furthermore, to investigate the condition of effective treatment, the reasons why donepezil treatment was discontinued in the DrG were examined.

Results:  The most frequent reason for discontinuation was the appearance of behavioral and psychiatric symptoms of dementia (BPSD), which were more frequently observed in the DrG. Although depression and/or disinclination were more frequent in the MG, hyperactivity was more frequent in the DeG and DrG. Before treatment, patients in the DrG exhibited significantly lower scores on the MMSE than did patients in the MG and DeG. Upon examination 4 months after starting treatment, patients in the MG showed cognitive improvement on the MMSE and RCI, whereas those in the DeG showed cognitive deterioration on the MMSE.

Conclusion:  The results of the present study suggest that when a short‐term beneficial effect of the donepezil on cognitive functions is seen, long‐term effect may also be expected at 2 years. Periodic clinical evaluation and examination of cognitive function is indispensable for effective donepezil treatment.
Bone quality assessment based on cone beam computed tomography imaging
Authors: Hua Yan , Nackaerts Olivia , Duyck Joke , Maes Frederik , Jacobs Reinhilde
Published: March 2009

Objectives: The aim of this in vitro study was to investigate the accuracy of fractal analysis and morphometry for bone quality assessment as measured with dual energy X‐ray absorptiometry (DXA).

Material and methods: Nineteen mandibular bone samples were used for the creation of artificial bone lesions (n=5) or decalcification (n=12) to simulate osteoporosis; two samples were used as controls. Cone beam computed tomography (CBCT) and DXA scans were made before and after processing the samples. The image data obtained from the CBCT scans were used to calculate the mean fractal dimension (FD), bone area and density (morphometric analysis) of the samples. Bone mineral density (BMD) was obtained from the DXA scans and set as a reference value for bone quality. The correlation between BMD and FD and between BMD and morphometric results were calculated.

Results: A significant correlation between FD and BMD (ρ=+0.71 to +0.75; P<0.05) was observed. Bone area and BMD of the specimens (ρ=+0.69 to +0.85; P<0.05) were also significantly related, in contrast to the density analysis, for which no significant correlation to BMD was found.

Conclusions: The results of this study suggest that fractal analysis and bone area measurement have potential to evaluate bone quality on CBCT images, while density measurement does not seem to be valid.
Tissue engineering of periosteal cell membranes in vitro
Authors: Warnke Patrick H. , Douglas Timothy , Sivananthan Sureshan , Wiltfang Jörg , Springer Ingo , Becker Stephan T.
Published: March 2009

Objectives: The cultivation of bone is a major focus in tissue engineering and oral implantology. Without a periosteal layer, instant or rapid development of a substantial cortical layer is unlikely for engineered bone grafts. The aim of this study was to test the ability of four collagen membranes to support and promote the proliferation of human periosteal cells.

Materials and methods: Human periosteum cells were cultured using an osteogenic medium consisting of Dulbecco's modified Eagle's medium supplemented with fetal calf serum, penicillin, streptomycin and ascorbic acid at 37°C with 5% CO2. Four collagen membranes served as scaffolds: Bio‐Gide, Chondro‐Gide, Tutodent and Ossix Plus. Cell vitality was assessed by fluorescin diacetate (FDA) and propidium iodide (PI) staining, biocompatibility with LDH and BrdU, MTT, WST tests and scanning electron microscopy (SEM).

Results: After 24 h, all probes showed viable periosteal cells. All biocompatibility tests revealed that proliferation on all membranes after treatment with eluate from membranes after a 24‐h immersion in a serum‐free cell culture medium was similar to the controls. Periosteal cells formed layers covering the surfaces of all four membranes 7 days after seeding in SEM.

Conclusion: It can be concluded from our data that the collagen membranes can be used as scaffolds for the cultivation of periosteum layers with a view to creating cortical bone using tissue‐engineering methods.
The role of CD44 in cutaneous inflammation
Authors: Man Mona , Elias Peter M. , Man Wenyan , Wu Yan , Bourguignon Lilly Y. W. , Feingold Kenneth R. , Man Mao‐Qiang
Published: March 2009

Abstract:  CD44 is a transmembrane glycoprotein expressed in various tissues including the skin. Previous studies indicated that CD44 is required for epidermal permeability barrier homeostasis and keratinocyte differentiation. Yet, while some studies have demonstrated that CD44 is critical for the development of inflammation, others have shown that CD44 is not essential for the development of cutaneous inflammation. In this study, we evaluated the changes in epidermal CD44 expression in a variety of skin inflammatory models and determined whether CD44 is required for the development of cutaneous inflammation. Inflammatory responses were compared in CD44 KO versus wild‐type mice in acute models of irritant and allergic contact dermatitis, as well as in a subacute allergic contact dermatitis induced by repeated hapten treatment. Inflammatory responses were assessed by measuring ear thickness and epidermal hyperplasia in haematoxylin & eosin‐stained sections. Our results demonstrate that: (i) epidermal CD44 expression increases in both acute and subacute cutaneous inflammatory models; and (ii) acute disruption of the epidermal permeability barrier function increases epidermal CD44 expression. Whereas inflammatory responses did not differ between CD44 KO and wild‐type mice in acute models of irritant and allergic contact dermatitis, both inflammatory responses and epidermal hyperplasia increased in CD44 KO mice following repeated hapten challenges. These results show first, that permeability barrier disruption and inflammation stimulate epidermal CD44 expression, and second, that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model.
Sequential Regulation of DOCK2 Dynamics by Two Phospholipids During Neutrophil Chemotaxis
Authors: Nishikimi Akihiko , Fukuhara Hideo , Su Wenjuan , Hongu Tsunaki , Takasuga Shunsuke , Mihara Hisashi , Cao Qinhong , Sanematsu Fumiyuki , Kanai Motomu , Hasegawa Hiroshi , Tanaka Yoshihiko , Shibasaki Masakatsu , Kanaho Yasunori , Sasaki Takehiko , Frohman Michael A. , Fukui Yoshinori
Published: March 2009

During chemotaxis, activation of the small guanosine triphosphatase Rac is spatially regulated to organize the extension of membrane protrusions in the direction of migration. In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor. Upon stimulation, we found that DOCK2 rapidly translocated to the plasma membrane in a phosphatidylinositol 3,4,5-trisphosphate–dependent manner. However, subsequent accumulation of DOCK2 at the leading edge required phospholipase D–mediated synthesis of phosphatidic acid, which stabilized DOCK2 there by means of interaction with a polybasic amino acid cluster, resulting in increased local actin polymerization. When this interaction was blocked, neutrophils failed to form leading edges properly and exhibited defects in chemotaxis. Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis.
Asymmetric Autocatalysis Triggered by Carbon Isotope (
13
C/
12
C) Chirality
Authors: Kawasaki Tsuneomi , Matsumura Yukari , Tsutsumi Takashi , Suzuki Kenta , Ito Masateru , Soai Kenso
Published: March 2009

The origin of chirality in asymmetric autocatalysis is due to carbon isotope substitution.
ON THE ASPHERICITY OF A FAMILY OF RELATIVE GROUP PRESENTATIONS
Authors: DAVIDSON PETER J.
Published: March 2009

Excluding four unresolved cases, we give a classification of asphericity in relative presentations of the form 〈H, t; tnat-1b〉 where the orders of a and b are both at least 3.
OPENED MODULAR NUMERICAL SEMIGROUPS WITH A GIVEN MULTIPLICITY
Authors: ROSALES J. C. , VASCO P.
Published: March 2009

Let ℕ be the set of nonnegative integers and let I be an interval of positive rational numbers. Then [Formula: see text] is a numerical semigroup. In this paper we study the multiplicity of the numerical semigroups of the form [Formula: see text], where a and b are integers such that 2 ≤ a < b. We also see the connection between the multiplicity and the Frobenius number of this type of semigroups.
THE TRANSMUTATION METHOD AND SCHRÖDINGER EQUATION WITH PERTURBED EXACTLY SOLVABLE POTENTIAL
Authors: KOYUNBAKAN H.
Published: March 2009

In this paper, it is proved the existence of a transmutation operator between two schrödinger equations with perturbed exactly solvable potential. An explicit formula for the solution of nucleus function by using Varsha and Jafari's method is also provided.
UNIVERSAL CODOMAINS TO REPRESENT INTERVAL ORDERS
Authors: CANDEAL JUAN CARLOS , GARCÍA JAVIER GUTIÉRREZ , INDURÁIN ESTEBAN
Published: March 2009

Given a binary relation defined on a set, we study its representability by means of a monotonic function that takes values on a suitable universal codomain (that depends on the kind of relation considered). We pay an special attention to the representability of interval orders, studying their alternative universal codomains, some of them equivalent to the set of symmetric triangular fuzzy numbers.
WAVELET-FACE BASED SUBSPACE LDA METHOD TO SOLVE SMALL SAMPLE SIZE PROBLEM IN FACE RECOGNITION
Authors: CHEN WEN-SHENG , HUANG JIAN , ZOU JIN , FANG BIN
Published: March 2009

Linear Discriminant Analysis (LDA) is a popular statistical method for both feature extraction and dimensionality reduction in face recognition. The major drawback of LDA is the so-called small sample size (3S) problem. This problem always occurs when the total number of training samples is smaller than the dimension of feature space. Under this situation, the within-class scatter matrix Sw becomes singular and LDA approach cannot be implemented directly. To overcome the 3S problem, this paper proposes a novel wavelet-face based subspace LDA algorithm. Wavelet-face feature extraction and dimensionality reduction are based on two-level D4-filter wavelet transform and discarding the null space of total class scatter matrix St. It is shown that our obtained projection matrix satisfies the uncorrelated constraint conditions. Hence in the sense of statistical uncorrelation, this projection matrix is optimal. The proposed method for face recognition has been evaluated with two public available databases, namely ORL and FERET databases. Comparing with existing LDA-based methods to solve the 3S problem, our method gives the best performance.
Blood Vessel Maturation in Human Uveal Melanoma: Spatial Distribution of Neovessels and Mature Vasculature
Authors: Piña Yolanda , Cebulla Colleen M. , Murray Timothy G. , Alegret Armando , Dubovy Sander R. , Boutrid Hinda , Feuer William , Mutapcic Lejla , Jockovich Maria-Elena
Published: March 2009

Purpose: The aims of this study are (1) to evaluate the spatial distribution of neovessels and mature vessels in human uveal melanoma tumors and (2) to determine whether vessel maturation is associated with the major indicators for poor prognosis. Methods: Immunohistochemical analyses were performed on human tissue specimens from enucleated eyes (n = 14) to assess total vessels, neovessels, mature vessels, and cell proliferation. Tumor morphology was analyzed by hematoxylin and eosin and modified periodic acid-Schiff (PAS) staining.The spatial distribution of neovessels and mature vessels was analyzed by immunohistochemistry, and correlated with major indicators of poor prognosis (i.e., aggressive PAS patterns, epithelioid cytology, mitotic figures, extraocular extension, anterior tumor location, ciliary body involvement, large tumor size, cell proliferation, and angiogenic activity). Results: Neovesseldensity was greater than mature vessel density in apical (p = 0.17), central (p = 0.036), and peripheral (p = 0.31) regions of the tumors, while mature vessel density was greater than neovessel density in basal areas of the tumor (p = 0.47). This pattern indicated that vessel maturation begins at the base of the tumor and later extends to the peripheral and apical regions. The difference between mature and neovessel densities for the apical (–0.8 ± 1.9) and central areas (–0.8 ± 1.3) of the tumor was significantly higher than the difference obtained for the basal area (0.3 ± 1.6; p = 0.014 and p = 0.012, respectively), indicating a higher density of mature vessels compared to neovessels at the base. Statistical correlations were found between mature vessel density and tumor size (r = 0.48, p = 0.084), cell proliferation (r = 0.62, p = 0.042), and mitotic figures (r = 0.76, p = 0.001). Conclusions: Significant differences exist in the spatial distribution of mature versus neovessels in human uveal melanoma. Vessel maturation is associated with known clinical and pathologic indicators of poor prognosis (e.g., cell proliferation). Antiangiogenic therapy should be considered for the treatment of ocular malignancies; however, the results of this study indicate that blood vessel maturation heterogeneity may limit the efficacy of vessel targeting agents.
Trends in Transfusion-Transmitted Viral Infections from 2001 to 2006 in Ibadan, Nigeria
Authors: Fasola Foluke A. , Kotila Taiwo R. , Akinyemi Joshua O.
Published: March 2009

Objective: Screening of blood before transfusion is an effective strategy to reduce transfusion-transmitted viruses. However, reports on viral marker trends among the donor population are scarce. This study looked at trends in the seroprevalence of hepatitis B (HBV) and C (HCV) and human immunodeficiency virus (HIV). Method: This is a retrospective study among blood donors at a tertiary hospital in Nigeria. We used the blood bank records to calculate yearly seroprevalence rates for HBV, HCV and HIV per 100 donations from 2001 to 2006. Results: A total of 33,682 prospective donors were screened, of which 13.2% were positive for HBsAg. The overall seroprevalence rates for HIV and HCV were 7.66% and 3.69%, respectively. HIV seroprevalence rose from 4.25% in 2001 to peak at 12.64% in 2003, before a steep drop to 6.35% in 2004 and a gradual decline to 5.70% in 2006 (p < 0.05). Conclusion: The seroprevalence rates for HIV and HBsAg fluctuated greatly during the study period while the seroprevalence of HCV was consistent. The screening kits used may be partly responsible for these fluctuations. Innovative programs for donor education, with the use of a formal questionnaire in donor selection, are recommended to ensure a safe donor population.
Subcellular Mislocalization of Mutant Hepatitis B X Proteins Contributes to Modulation of STAT/SOCS Signaling in Hepatocellular Carcinoma
Authors: Bock C.-Thomas , Toan Nguyen L. , Koeberlein Bernd , Song Le H. , Chin Ruth , Zentgraf Hanswalter , Kandolf Reinhard , Torresi Joseph
Published: March 2009

Objective: The hepatitis B virus X (HBx) protein plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). One potential mechanism by which HBx can cause liver cancer may involve intracellular distribution and consecutively modulation of the proliferative important STAT/SOCS signaling with upregulation of STAT3. Methods: 153 Vietnamese HBV-infected patients, including 48 patients with HCC, were analyzed. HBx sequences were determined by sequencing and subcloned for functional experiments. Intracellular localization of HBx mutants was determined by immunofluorescence assays. The impact of HBx mutants on JAK/STAT/SOCS signaling was investigated using Western blot and PCR analyses. Results: In 4/48 HCC patients, truncated HBx together with full-length mutated HBx proteins were observed. Expression of HBx mutant proteins demonstrated an atypical nuclear and perinuclear localization. Functional experiments to determine the effect of HBx mutants on STAT/SOCS signaling demonstrated a significantly increased upregulation of STAT3 activation (p > 0.001) in comparison to wild-type (wt)-HBx. STAT1 was not activated either by wt-HBx or HBx mutants. Interestingly, SOCS1 and SOCS3 expression was not activated by wt-HBx and HBx mutants. Conclusions: Our results suggest that atypical nuclear/perinuclear localization of HBx mutants might be responsible for an enhanced activation of STAT3, inhibition of STAT1 and silencing of SOCS1/SOCS3 expression. This observation points to an active role of HBx mutants in hepatocarcinogenesis that involves dysregulation of STAT/SOCS signaling.
Association of a 5-HT1Dβ Receptor Gene Polymorphism with Obsessive-Compulsive Disorder in Korean Male Subjects
Authors: Kim Se Joo , Namkoong Kee , Kang Jee In , Kim Chan-Hyung
Published: March 2009

The 5-HT1Dβ receptor gene appears to be particularly interesting in the pathophysiology of obsessive-compulsive disorder (OCD). The 5-HT1Dβ receptor is a terminal autoreceptor involved in the regulation of serotonin synthesis and release. We performed an association study of the G861C single nucleotide polymorphism (SNP) of the 5-HT1Dβ receptor in 167 male Korean OCD subjects and in 107 controls. Individuals with the G allele had an increased chance of having OCD (OR 1.49, 95% CI 1.05–2.10). Our findings suggest an association between the G861C SNP of the 5-HT1Dβ receptor and males with OCD. In the future, other tag SNPs that cover the entire 5-HT1Dβ gene region as well as additional SNPs that are supposed to have meaningful functions should be investigated in both male and female OCD subjects.
Therapeutic Neovascularization by Nanotechnology-Mediated Cell-Selective Delivery of Pitavastatin Into the Vascular Endothelium
Authors: Kubo Mitsuki , Egashira Kensuke , Inoue Takahiro , Koga Jun-ichiro , Oda Shinichiro , Chen Ling , Nakano Kaku , Matoba Tetsuya , Kawashima Yoshiaki , Hara Kaori , Tsujimoto Hiroyuki , Sueishi Katsuo , Tominaga Ryuji , Sunagawa Kenji
Published: March 2009

Objective—

Recent clinical studies of therapeutic neovascularization using angiogenic growth factors demonstrated smaller therapeutic effects than those reported in animal experiments. We hypothesized that nanoparticle (NP)-mediated cell-selective delivery of statins to vascular endothelium would more effectively and integratively induce therapeutic neovascularization.

Methods and Results—

In a murine hindlimb ischemia model, intramuscular injection of biodegradable polymeric NP resulted in cell-selective delivery of NP into the capillary and arteriolar endothelium of ischemic muscles for up to 2 weeks postinjection. NP-mediated statin delivery significantly enhanced recovery of blood perfusion to the ischemic limb, increased angiogenesis and arteriogenesis, and promoted expression of the protein kinase Akt, endothelial nitric oxide synthase (eNOS), and angiogenic growth factors. These effects were blocked in mice administered a nitric oxide synthase inhibitor, or in eNOS-deficient mice.

Conclusions—

NP-mediated cell-selective statin delivery may be a more effective and integrative strategy for therapeutic neovascularization in patients with severe organ ischemia.
Site-Specific Antiatherogenic Effect of the Antioxidant Ebselen in the Diabetic Apolipoprotein E–Deficient Mouse
Authors: Chew Phyllis , Yuen Derek Y.C. , Koh Philip , Stefanovic Nada , Febbraio Mark A. , Kola Ismail , Cooper Mark E. , de Haan Judy B.
Published: March 2009

Objective—

Recently we showed that lack of the antioxidant enzyme glutathione peroxidase-1 (GPx1) accelerates atherosclerosis and upregulates proatherogenic pathways in diabetic apoE/GPx1-deficient double-knockout mice, thereby establishing GPx1 as an important therapeutic target. In vivo studies now investigate ebselen, a seleno-organic GPx1-mimetic, for its potential to reduce diabetes-associated atherosclerosis.

Methods and Results—

Lesions were significantly increased in diabetic apoE
−/−
aortas (
P
<0.001) compared with nondiabetic controls after 20 weeks of diabetes. Ebselen-gavage significantly reduced total aortic lesions (
P
<0.001), with significant regional reductions in the arch (
P
<0.001), thoracic (
P
<0.001), and abdominal regions (
P
<0.05), but not within the aortic sinus of diabetic apoE
−/−
mice. These reductions were accompanied by significantly lower nitrotyrosine and Nox2 levels, reduced proatherogenic cellularity (macrophages and SMCs), and reduced expression of the proatherogenic mediator RAGE. Within the aortic sinus, ebselen reduced nitrotyrosine, Nox2, and VEGF levels but had no effect on RAGE. Studies in HAECs show that ebselen abrogates H
2
O
2
-induced increases in P-IKK, P-JNK, TNF-α, and Nox2.

Conclusions—

Ebselen reduces atherosclerotic lesions in most regions of diabetic apoE
−/−
aorta, except within the aortic sinus, suggesting its effectiveness as a potential antiatherogenic therapy in diabetic-macrovascular disease. Ebselen may elicit its effect via modulation of transcription factors such as NF-κB and AP-1.
Stochastic Variance Models in Discrete Time with Feedforward Neural Networks
Authors: Andoh Charles
Published: March 2009

The study overcomes the estimation difficulty in stochastic variance models for discrete financial time series with feedforward neural networks. The volatility function is estimated semiparametrically. The model is used to estimate market risk, taking into account not only the time series of interest but extra information on the market. As an application, some stock prices series are studied and compared with the nonlinear ARX-ARCHX model.
Reducing the Health Risks of Diabetes
Authors: Williams Geoffrey C. , Patrick Heather , Niemiec Christopher P. , Williams L. Keoki , Divine George , Lafata Jennifer Elston , Heisler Michele , Tunceli Kaan , Pladevall Manel
Published: March 2009

Purpose

The purpose of this study is to apply the self-determination theory (SDT) model of health behavior to predict medication adherence, quality of life, and physiological outcomes among patients with diabetes.

Methods

Patients with diabetes (N = 2973) receiving care from an integrated health care delivery system in 2003 and 2004 were identified from automated databases and invited to participate in this study. In 2005, patients responded to a mixed telephone-and-mail survey assessing perceived autonomy support from health care providers, autonomous self-regulation for medication use, perceived competence for diabetes self-management, medication adherence, and quality of life. In 2006, pharmacy claims data were used to indicate medication adherence, and patients' non—high-density lipoprotein (HDL) cholesterol, A1C, and glucose levels were assessed.

Results

The SDT model of health behavior provided adequate fit to the data. As hypothesized, perceived autonomy support from health care providers related positively to autonomous self-regulation for medication use, which in turn related positively to perceived competence for diabetes self-management. Perceived competence then related positively to quality of life and medication adherence, and the latter construct related negatively to non-HDL cholesterol, A1C, and glucose levels.

Conclusions

Health care providers' support for patients' autonomy and competence around medication use and diabetes self-management related positively to medication adherence, quality of life, and physiological outcomes among patients with diabetes.
Love as Redemption
Authors: Smith Glenn D.
Published: March 2009

This research documents the American Dream in two popular biopics: Ray (2004) and Walk the Line (2005). In both films, the American Dream, framed by the ideology of individuality, follows a particular trajectory: Struggle, individual effort, responsibility, and talent lead to material wealth, but the protagonists' immoral behaviors overwhelm them, thus creating a host of professional and personal problems. The relevance of racism and class struggle, long identified as significant barriers to upward mobility, is minimized for a more personal issue, psychological trauma, to explain their moral declines. Both films resolve the natural tensions between the material (individualism) and the moral (brotherhood) by introducing the Hollywood love story as an acceptable narrative for the lead character's redemption. The mythology allows for a more feminine narrative (heterosexual romantic love) as moral resolution, one that avoids the more complicated notions of brotherhood (racial and class equality) as part of the ideological equation.
Advance care planning in care homes for older people: an English perspective
Authors: Froggatt K , Vaughan S , Bernard C , Wild D
Published: March 2009

Advance care planning (ACP) as a process of discussing and recording wishes for future care and treatment is increasingly being promoted and discussed in the UK, reflecting recent changes in legislation. This study describes current ACP practice in care homes for older people drawing on data from a questionnaire survey ( n = 213) of, and interviews ( n = 15) with, care home managers. Whilst consultation about general care is taking place in the majority of homes surveyed using both formal and informal processes, the number of residents that have completed any ACP processes varies. Managers face intrinsic and extrinsic challenges related to the ascertaining of, and the implementing of wishes as they address ACP in the care home context. Until these wider contextual factors are addressed it will be difficult for staff in care homes to effectively undertake and implement ACP in care homes.
The Role of Championship in the Mainstreaming of Sustainable Investment (SI)
Authors: Juravle Carmen , Lewis Alan
Published: March 2009

The present study identifies the strategies that individuals committed to the cause of Sustainable Investment (SI) use when attempting to persuade institutional investors (e.g., pension funds) to invest in socially and environmentally responsible ways. This article is based on interviews with 15 pioneers of the SI movement in the United Kingdom. Building on the literature on issue-selling, green championship, and corporate social responsibility, this study identifies four tactics that pioneers have employed to “sell” SI in investment institutions: making the business case for SI; forming internal coalitions with mainstream investment professionals; industry networking; gaining credible expertise. The results also suggest that market short-termism and internal organizational contexts dominated by a lack of moral engagement and disempowerment of SI teams are factors that impede champions' efforts. The article opens new avenues for research and recommends ways in which organizational and institutional impediments to SI may be overcome.
Induction of CCL20 production by Kaposi sarcoma–associated herpesvirus: role of viral FLICE inhibitory protein K13-induced NF-κB activation
Authors: Punj Vasu , Matta Hittu , Schamus Sandra , Yang Tianbing , Chang Yuan , Chaudhary Preet M.
Published: March 2009

Kaposi sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent of Kaposi sarcoma (KS), an angioproliferative lesion characterized by dramatic angiogenesis and inflammatory infiltration. In this study, we report that expression of chemokine CCL20, a potent chemoattractant of dendritic cells and lymphocytes, is strongly induced in cultured cells either by KSHV infection or on ectopic expression of viral FLICE inhibitory protein K13. This induction is caused by transcriptional activation of CCL20 gene, which is mediated by binding of the p65, p50, and c-Rel subunits of the transcription factor nuclear factor–κB (NF-κB) to an atypical NF-κB–binding site present in the CCL20 gene promoter. The CCL20 gene induction is defective in K13 mutants that lack NF-κB activity, and can be blocked by specific genetic and pharmacologic inhibitors of the NF-κB pathway. CCR6, the specific receptor for CCL20, is also induced in cultured cells either by KSHV infection or on K13 expression. Finally, expression of CCL20 and CCR6 is increased in clinical samples of KS. These results suggest that KSHV and K13-mediated induction of CCL20 and CCR6 may contribute to the recruitment of dendritic cells and lymphocytes into the KS lesions, and to tumor growth and metastases.
Staphylococcus aureus immunodominant surface antigen B is a cell-surface associated nucleic acid binding protein
Authors: Mackey-Lawrence Nicole M , Potter Denise E , Cerca Nuno , Jefferson Kimberly K
Published: March 2009

Background

Staphylococcus aureus immunodominant surface antigen B (IsaB) elicits an immune response during septicemia and is generally classified as a virulence factor, but its biological function remains completely undefined. In an attempt to identify staphylococcal RNA-binding proteins, we designed an RNA Affinity Chromatography assay and subsequently isolated IsaB.

Results

Western analysis indicated that IsaB was both secreted and cell-surface associated. Gel Shift analysis confirmed the RNA binding activity but revealed that IsaB bound to any nucleic acid without sequence specificity. IsaB exhibited the highest affinity for double-stranded DNA followed by single-stranded DNA and RNA. Because extracellular DNA has been shown to play a role in biofilm formation, we investigated the biofilm-forming capacity of an isogenic isaB deletion mutant but we found that IsaB did not contribute to biofilm formation under any conditions tested.

Conclusion

IsaB is an extracellular nucleic acid binding protein, with little to no sequence specificity, but its role in virulence remains unclear.
Tat-Binding Protein-1 (TBP-1), an ATPase of 19S Regulatory Particles of the 26S Proteasome, Enhances Androgen Receptor Function in Cooperation with TBP-1-Interacting Protein/Hop2
Authors: Satoh Tetsurou , Ishizuka Takahiro , Tomaru Takuya , Yoshino Satoshi , Nakajima Yasuyo , Hashimoto Koshi , Shibusawa Nobuyuki , Monden Tsuyoshi , Yamada Masanobu , Mori Masatomo
Published: March 2009

The 26S proteasome, which degrades ubiquitinated proteins, appears to contribute to the cyclical loading of androgen receptor (AR) to androgen response elements of target gene promoters; however, the mechanism whereby the 26S proteasome modulates AR recruitment remains unknown. Using yeast two-hybrid screening, we previously identified Tat-binding protein-1 (TBP-1), an adenosine triphosphatase of 19S regulatory particles of the 26S proteasome, as a transcriptional coactivator of thyroid hormone receptor. Independently, TBP-1-interacting protein (TBPIP) was also identified as a coactivator of several nuclear receptors, including AR. Here, we investigated whether TBP-1 could interact with and modulate transcriptional activation by AR cooperatively with TBPIP. TBP-1 mRNA was ubiquitously expressed in human tissues, including the testis and prostate, as well as in LNCaP cells. TBP-1 directly bound TBPIP through the amino-terminal domain possessing the leucine zipper structure. AR is physically associated with TBP-1 and TBPIP in vitro and in LNCaP cells. TBP-1 similarly and additively augmented AR-mediated transcription upon coexpression with TBPIP, and the ATPase domain, as well as leucine zipper structure in TBP-1, was essential for transcriptional enhancement. Overexpression of TBP-1 did not alter AR protein and mRNA levels. In the chromatin immunoprecipitation assay, TBP-1 was transiently recruited to the proximal androgen response element of the prostate-specific antigen gene promoter in a ligand-dependent manner in LNCaP cells. These findings suggest that a component of 19S regulatory particles directly binds AR and might participate in AR-mediated transcriptional activation in cooperation with TBPIP.