bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells
Authors: Liu XueQiao , Cohen Jeffrey I.
Published: November 2013

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.
Novel Neuroprotective GSK-3β Inhibitor Restricts Tat-Mediated HIV-1 Replication
Authors: Guendel Irene , Iordanskiy Sergey , Van Duyne Rachel , Kehn-Hall Kylene , Saifuddin Mohammed , Das Ravi , Jaworski Elizabeth , Sampey Gavin C. , Senina Svetlana , Shultz Leonard , Narayanan Aarthi , Chen Hao , Lepene Benjamin , Zeng Chen , Kashanchi Fatah
Published: November 2013

The implementation of new antiretroviral therapies targeting transcription of early viral proteins in postintegrated HIV-1 can aid in overcoming current therapy limitations. Using high-throughput screening assays, we have previously described a novel Tat-dependent HIV-1 transcriptional inhibitor named 6-bromoindirubin-3′-oxime (6BIO). The screening of 6BIO derivatives yielded unique compounds that show potent inhibition of HIV-1 transcription. We have identified a second-generation derivative called 18BIOder as an inhibitor of HIV-1 Tat-dependent transcription in TZM-bl cells and a potent inhibitor of GSK-3β kinasein vitro. Structurally, 18BIOder is half the molecular weight and structure of its parental compound, 6BIO. More importantly, we also have found a different GSK-3β complex present only in HIV-1-infected cells. 18BIOder preferentially inhibits this novel kinase complex from infected cells at nanomolar concentrations. Finally, we observed that neuronal cultures treated with Tat protein are protected from Tat-mediated cytotoxicity when treated with 18BIOder. Overall, our data suggest that HIV-1 Tat-dependent transcription is sensitive to small-molecule inhibition of GSK-3β.
Evolution and Diversity in Human Herpes Simplex Virus Genomes
Authors: Szpara Moriah L. , Gatherer Derek , Ochoa Alejandro , Greenbaum Benjamin , Dolan Aidan , Bowden Rory J. , Enquist Lynn W. , Legendre Matthieu , Davison Andrew J.
Published: November 2013

Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide.
TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein
Authors: Heurich Adeline , Hofmann-Winkler Heike , Gierer Stefanie , Liepold Thomas , Jahn Olaf , Pöhlmann Stefan
Published: November 2013

The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-CoV S protein (SARS-S) activation has not been determined. Here, we show that arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for cleavage by TMPRSS2 and HAT and that ACE2 processing is required for augmentation of SARS-S-driven entry by these proteases. In contrast, ACE2 cleavage was dispensable for activation of the viral S protein. Expression of TMPRSS2 increased cellular uptake of soluble SARS-S, suggesting that protease-dependent augmentation of viral entry might be due to increased uptake of virions into target cells. Finally, TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry. Collectively, our results in conjunction with those of previous studies indicate that TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion. These observations have interesting implications for the development of novel therapeutics. In addition, they should spur efforts to determine whether receptor cleavage promotes entry of other coronaviruses, which use peptidases as entry receptors.
Discovery of a Novel Bottlenose Dolphin Coronavirus Reveals a Distinct Species of Marine Mammal Coronavirus in Gammacoronavirus
Authors: Woo Patrick C. Y. , Lau Susanna K. P. , Lam Carol S. F. , Tsang Alan K. L. , Hui Suk-Wai , Fan Rachel Y. Y. , Martelli Paolo , Yuen Kwok-Yung
Published: November 2013

While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (
Tursiops aduncus
), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22-positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 × 10
3
to 1 × 10
5
copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (

K
s

) to the number of nonsynonymous substitutions per nonsynonymous site (

K
a

) in multiple regions of the genome, especially the S gene (

K
a

/

K
s

ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species,
Cetacean coronavirus
, in
Gammacoronavirus
, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species,
Avian coronavirus
, in
Gammacoronavirus
.
Histone Deacetylase Classes I and II Regulate Kaposi's Sarcoma-Associated Herpesvirus Reactivation
Authors: Shin Hye Jin , DeCotiis Jennifer , Giron Mario , Palmeri Diana , Lukac David M.
Published: November 2013

In primary effusion lymphoma (PEL) cells infected with latent Kaposi's sarcoma-associated herpesvirus (KSHV), the promoter of the viral lytic switch gene, Rta, is organized into bivalent chromatin, similar to cellular developmental switch genes. Histone deacetylase (HDAC) inhibitors (HDACis) reactivate latent KSHV and dramatically remodel the viral genome topology and chromatin architecture. However, reactivation is not uniform across a population of infected cells. We sought to identify an HDACi cocktail that would uniformly reactivate KSHV and reveal the regulatory HDACs. Using HDACis with various specificities, we found that class I HDACis were sufficient to reactivate the virus but differed in potency. Valproic acid (VPA) was the most effective HDACi, inducing lytic cycle gene expression in 75% of cells, while trichostatin A (TSA) induced less widespread lytic gene expression and inhibited VPA-stimulated reactivation. VPA was only slightly superior to TSA in inducing histone acetylation of Rta's promoter, but only VPA induced significant production of infectious virus, suggesting that HDAC regulation after Rta expression has a dramatic effect on reactivation progression. Ectopic HDACs 1, 3, and 6 inhibited TPA-stimulated KSHV reactivation. Surprisingly, ectopic HDACs 1 and 6 stimulated reactivation independently, suggesting that the stoichiometries of HDAC complexes are critical for the switch. Tubacin, a specific inhibitor of the ubiquitin-binding, proautophagic HDAC6, also inhibited VPA-stimulated reactivation. Immunofluorescence indicated that HDAC6 is expressed diffusely throughout latently infected cells, but its expression level and nuclear localization is increased during reactivation. Overall, our data suggest that inhibition of HDAC classes I and IIa and maintenance of HDAC6 (IIb) activity are required for optimal KSHV reactivation.
A Novel Strategy To Develop a Robust Infectious Hepatitis C Virus Cell Culture System Directly from a Clinical Isolate
Authors: Lu Jie , Xiang Yu , Tao Wanyin , Li Qingchao , Wang Na , Gao Yongfeng , Xiang Xiaogang , Xie Qing , Zhong Jin
Published: November 2013

Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases. Progress in the HCV field was greatly enhanced by constructing infectious cDNA clone of JFH-1. Since then, JFH-1-based intra- and intergenotypic recombinants have been developed, and this permitted the study of vaccines and antiviral inhibitors for all genotypes. Recently, highly efficient HCV culture systems have been established by using consensus sequence-based clones. We developed a novel strategy to construct infectious HCV cDNA clone by combining functional screening of sequences directly from a genotype 2a clinical isolate (PR63) and cell culture adaptation. Using JFH-1 cDNA as the starting backbone, we sequentially replaced the JFH-1 fragments with a sequence from the pools of PR63 sequences. Through engineering adaptive mutations that improve HCV infectivity, we finally established a full-length cell culture-derived infectious clone of PR63, named PR63cc, that could efficiently produce virus particles in Huh7-derived cells, with peak titers of 1.6 × 10
5
focus-forming units/ml. The PR63cc could be neutralized by an anti-E2 antibody and inhibited by antiviral agents but appeared more resistant to an NS5A inhibitor than JFH-1. In summary, we developed a new approach to construct an infectious HCV cDNA clone that can produce viruses efficiently in cell culture. This approach could be applied to other viral isolates, with potential implications for individualized treatments of HCV patients.
Refractory pruritus in primary biliary cirrhosis
Authors: Pinheiro Nuno Cercas , Marinho Rui Tato , Ramalho Fernando , Velosa José
Published: November 2013

Pruritus is a major symptom of primary biliary cirrhosis, cholestatic autoimmune disease which affects mostly middle-age women. Often, it can be severe and refractory to multiple treatments, and mostly affecting the patient’s health-related quality of life. Intense pruritus can be itself an indication to liver transplantation, in extreme cases leading to suicide. Its physiopathology has not yet been fully elucidated, but recent studies added the elevation of autotaxin and lysophosphatidic acid to the group of classic mechanisms already linked to cholestatic pruritus. In this case report we illustrate how ultraviolet B phototherapy appears to successfully control severe pruritus and contribute to the healing of pruritic skin lesions caused by intense scratching. There is limited medical literature concerning this therapeutic approach on cholestatic pruritus, but we hope that further randomised controlled trials will successfully establish it as an effective treatment in the near future.
Successful treatment of acquired pure red cell aplasia with oral corticosteroids in a patient with B-cell CLL
Authors: Dharmshaktu Pramila , Gupta Naresh , Dhanwal Dinesh Kumar
Published: November 2013

We present the case of a 57-year-old male patient diagnosed with chronic lymphoid leukaemia (CLL) B-cell type along with moderate anaemia. On follow-up investigations the aetiology of anaemia turned out to be pure red cell aplasia (PRCA) on trephine bone biopsy with an elevated serum erythropoietin level. The patient received blood transfusion support. He showed remarkable improvement on oral corticosteroids (prednisolone 60 mg/daily dose) with no further requirement of blood transfusion over next 3 months. However, when the dose of steroid was tapered down to 10 mg/day, the anaemia reappeared. An increase in the dose of steroid brought the haemoglobin level back to normal. Anaemia in CLL can be due to many reasons, of which PRCA is an uncommon association occurring in only around 1% of patients with CLL and usually refractory to the conventional treatment with steroids. This PRCA secondary to CLL is considered to be immune in origin and a response to combination of immunosuppressive therapy such as steroids, cyclosporine, rituximab is anticipated. Our case responded completely to oral steroids alone.
Fibroepithelial polyp of the ureter
Authors: Sinha Rajan Kumar , Jindal Tarun , Kamal Mir Reza , Karmakar Dilip
Published: November 2013

A 36-year-old woman presented with haematuria and a bladder mass on ultrasonogram. Cystoscopy revealed a tumour, cauliflower in shape with smooth stalk coming out from the ureteric orifice. Stalk of the polyp was identified in proximal ureter by ureteroscopy. The mass was excised endoscopically.
DISPLACE: a dynamic, individual-based model for spatial fishing planning and effort displacement — integrating underlying fish population models
Authors: Bastardie Francois , Nielsen J. Rasmus , Miethe Tanja
Published: November 2013

We previously developed an individual-based model evaluating the bio-economic efficiency of fishing vessel movements from recent high resolution spatial fishery data. The assumption was constant underlying resource availability. Now, an advanced version considers the underlying size-based dynamics of the targeted stocks for Danish and German vessels harvesting the North Sea and Baltic Sea fish stocks. The stochastic fishing process is specific to the vessel catching power and to the encountered population abundances, based on disaggregated research survey data. The impact of the effort displacement on the fish stocks and the vessels’ economic consequences were evaluated by simulating individual choices of vessel speed, fishing grounds, and ports. Some scenarios led to increased energy efficiency and profit while others such as fishing closures or fishermen optimization sometimes lowered the revenue by altering the spatiotemporal effort allocation. On an individual scale, the simulations led to gains and losses due to either the interactions between vessels or to the alteration of individual patterns. We demonstrate that integrating the spatial activity of vessels and fish abundance dynamics allow for more realistic predictions of fishermen behaviour, profits, and stock abundance.
Assessment of local spatial and analytical variability in regional geochemical surveys with a simple sampling scheme
Authors: Garrett Robert G.
Published: November 2013

A procedure is presented for estimating the relative contributions of geochemical survey, local sampling, and analytical variability to total survey variability. Additionally, F-tests for the statistical significance of the variance components are undertaken to assist in determining if the survey data are fit for purpose in mapping exercises. Based on triplicate analyses, where one of the field duplicates is split to provide an analytical duplicate, the procedure is effective, both statistically and in terms of cost. Open Source, R, Analysis of Variance (ANOVA) software is available to undertake the statistical data investigation. Guidance rules are developed to help determine if the data should be transformed in order to satisfy the assumptions, normality and homoscedasticity, of the ANOVA method, and to accommodate the compositional, constant sum, nature of analytical geochemical data.
Tectonomagmatic evolution of the Early Ordovician suprasubduction-zone ophiolites of the Trondheim Region, Mid-Norwegian Caledonides
Authors: Slagstad Trond , Pin Christian , Roberts David , Kirkland Christopher L. , Grenne Tor , Dunning Greg , Sauer Simone , Andersen Tom
Published: November 2013

The Trondheim Region ophiolites in the Mid-Norwegian Caledonides represent variably tectonized ophiolite fragments. We present high-precision thermal-ionization mass spectrometry and secondary-ion mass spectrometry (SIMS) U–Pb zircon dates, whole-rock geochemical and Sm–Nd data and Lu–Hf zircon analyses that permit the timing and nature of various stages in the evolution of the ophiolite to be elucidated. Plagiogranite intrusions dated at 487 and 480 Ma have relatively juvenile Nd and Hf isotopic compositions (ε

Nd(
t
)

=6.3, ε

Hf(
t
)

=8.2–12.4). Geochemical data indicate a subduction-zone influence, suggesting formation in an oceanic back-arc setting. At 481 Ma, a granitoid body with a relatively strong unradiogenic Nd and Hf isotopic composition (ε

Nd(
t
)

=−2.6 to −4.0, ε

Hf(
t
)

=3.8–6.4) and subduction-zone geochemical signature intruded the ophiolite. We interpret this stage to reflect the formation or migration of an oceanic arc above a subduction zone influenced by continentally derived sediments. At
c.
475–465 Ma, a greenstone-dominated conglomerate and volcaniclastic sequence was deposited on the eroded ophiolite, indicating obduction between about 480 and 475 Ma. At
c.
468–467 Ma, the deformed ophiolite and its sedimentary cover was intruded by trondhjemite dykes and shoshonitic volcanic rocks with intermediate Nd and Hf isotopic compositions (ε

Nd(
t
)

=3.0–3.9, ε

Hf(
t
)

=4.4–10.2). We interpret this magmatism to reflect subduction-polarity reversal and establishment of a magmatic arc at the continental margin shortly after obduction.

Supplementary material:

Whole-rock geochemistry, Sm–Nd isotopic data, SHRIMP U–Pb zircon, TIMS U–Pb zircon and Lu–Hf isotopic data are available at
http://www.geolsoc.org.uk/SUP18689
.
Cellular calcium dynamics in lactation and breast cancer: from physiology to pathology
Authors: Cross Brandie M. , Breitwieser Gerda E. , Reinhardt Timothy A. , Rao Rajini
Published: November 2013

Breast cancer is the second leading cause of cancer mortality in women, estimated at nearly 40,000 deaths and more than 230,000 new cases diagnosed in the U.S. this year alone. One of the defining characteristics of breast cancer is the radiographic presence of microcalcifications. These palpable mineral precipitates are commonly found in the breast after formation of a tumor. Since free Ca2+ plays a crucial role as a second messenger inside cells, we hypothesize that these chelated precipitates may be a result of dysregulated Ca2+ secretion associated with tumorigenesis. Transient and sustained elevations of intracellular Ca2+ regulate cell proliferation, apoptosis and cell migration, and offer numerous therapeutic possibilities in controlling tumor growth and metastasis. During lactation, a developmentally determined program of gene expression controls the massive transcellular mobilization of Ca2+ from the blood into milk by the coordinated action of calcium transporters, including pumps, channels, sensors and buffers, in a functional module that we term CALTRANS. Here we assess the evidence implicating genes that regulate free and buffered Ca2+ in normal breast epithelium and cancer cells and discuss mechanisms that are likely to contribute to the pathological characteristics of breast cancer.
Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats
Authors: Lang Charles H. , Korzick Donna H.
Published: November 2013

The purpose of this study was to assess whether the deleterious effect of chronic alcohol consumption differs in adult and aged female rats. To address this aim, adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% total calories) or an isocaloric isonitrogenous control diet for 20 wk. Cardiac structure and function, assessed by echocardiography, as well as myocardial protein synthesis and proteolysis did not differ in either alcohol- versus control-fed adult rats or in adult versus aged control-fed rats. In contrast, cardiac function was impaired in alcohol-fed aged rats compared with age-matched control rats. Additionally, alcohol feeding decreased cardiac protein synthesis that was associated with decreased phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle RING-finger protein-1 (MuRF1). These changes were associated with increased regulated in development and DNA damage response 1 (REDD1) and phosphorylation of AMP-activated protein kinase (AMPK) but no increase in AKT or forkhead transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy (e.g., LC3B, Atg7, Atg12) and TNF-α were increased to a greater extent in alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an enhanced sensitivity to alcohol compared with adult animals. Our data are consistent with a model whereby alcohol increases proteolysis via FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore impairs formation of a functional preinitiation complex and protein synthesis.
Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis
Authors: Wang Xiao-Mei , Yao Min , Liu Shu-Xia , Hao Jun , Liu Qing-Juan , Gao Feng
Published: November 2013

Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short-hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt, and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling and annexin V/propidium iodide staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis.
Brown Fat Expresses Adiponectin in Humans
Authors: Iacobellis Gianluca , Di Gioia Cira , Petramala Luigi , Chiappetta Caterina , Serra Valentina , Zinnamosca Laura , Marinelli Cristiano , Ciardi Antonio , De Toma Giorgio , Letizia Claudio
Published: November 2013

The presence of brown adipose tissue (BAT) in humans is unclear. Pheochromocytomas (PHEO) are rare tumors of neuroectodermal origin which occur in 0.1-0.2% of patients with hypertension. We sought to evaluate the presence and activity of BAT surrounding adrenal PHEO in a well-studied sample of 11 patients who were diagnosed with PHEO and then underwent adrenalectomy. Areas of white fat (WAT) and BAT surrounding PHEO were obtained by Laser Capture Microdissection for analysis of uncoupling protein (UCP)-1 and adiponectin mRNA expression. Adiponectin and UCP-1 mRNA levels were significantly higher in BAT than in WAT (0.62 versus 0.15 and 362.4 versus 22.1, resp., for both). Adiponectin mRNA levels significantly correlated with urinary metanephrines (, ), vanilly mandelic acid (VMA) (, ), and serum adiponectin levels (, ). Serum adiponectin levels significantly decreased ( μg/mL versus  μg/mL, ) after adrenalectomy in PHEO subjects. This study provides the following findings: (1) BAT surrounding PHEO expresses adiponectin and UCP-1 mRNA, (2) expression of adiponectin mRNA is significantly higher in BAT than in WAT surrounding PHEO, and (3) catecholamines and serum adiponectin levels significantly correlate with BAT UCP-1 and adiponectin mRNA.
Levels of Inflammatory Cytokines in Type 2 Diabetes Patients with Different Urinary Albumin Excretion Rates and Their Correlation with Clinical Variables
Authors: Chen Fen-qin , Wang Jiao , Liu Xiao-bo , Ma Xiao-yu , Zhang Xiu-bin , Huang Ting , Ma Dong-wei , Wang Qiu-yue
Published: November 2013

Although the pathogenetic mechanism of DN has not been elucidated, an inflammatory mechanism has been suggested as a potential contributor. This study was designed to explore the relationship between low-grade inflammation and renal microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three groups according to UAE: a normal albuminuria group, a microalbuminuria group, and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP, TNF-α, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were measured in all subjects. Compared with the normal controls, levels of hs-CRP, TNF-α, uMCP-1, and SAA in T2DM patients were significantly higher. They were also elevated in the normal albuminuria group,P<0.05. Compared with the normal albuminuria group, levels of these inflammatory cytokines were significantly higher in the microalbuminuria and macroalbuminuria group,P<0.01. The macroalbuminuria group also showed higher levels than the microalbuminuria group,P<0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC. We noted no significance correlated with course, TG, or HDL-C. Only TNF-α; was positively correlated with HbA1c. This study revealed the importance of these inflammatory cytokines in DN pathogenesis. Further studies are needed to fully establish the potential of these cytokines as additional biomarkers for the development of DN.
Effect ofNelumbo nuciferaPetal Extracts on Lipase, Adipogenesis, Adipolysis, and Central Receptors of Obesity
Authors: Velusami Chandrasekaran Chinampudur , Agarwal Amit , Mookambeswaran Vijayalakshmi
Published: November 2013

N. nuciferais one among the important medicinal plants assessed for its antiobesity action in various preclinical models. The present study was aimed at investigating the antiobesity effect of methanol and successive water extracts of petals ofN. nuciferaby studying its effect on adipogenesis, adipolysis, lipase, serotonin (5-HT2C), cannabinoid (CNR2), melanocyte concentrating hormone (MCHR1), and melanocortin (MC4R) receptors. Both methanol and successive water extracts ofN. nuciferapetals had an effect on inhibition of lipid storage in adipocytes and on increasing lipolysis.N. nuciferapetal methanol extract exhibited the concentration-dependent inhibitory effect on lipase activity with an IC50value of 47 µg/mL.N. nuciferapetal extracts showed evident agonist and antagonist activity towards 5-HT2Cand CNR2receptors, respectively, while it showed no effect towards MCHR1and MC4R receptors. Overall, methanol extract ofN. nuciferapetals showed better activity than successive water extract.
Circulating C19MC MicroRNAs in Preeclampsia, Gestational Hypertension, and Fetal Growth Restriction
Authors: Hromadnikova Ilona , Kotlabova Katerina , Ondrackova Marketa , Kestlerova Andrea , Novotna Veronika , Hympanova Lucie , Doucha Jindrich , Krofta Ladislav
Published: November 2013

The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) in patients with established preeclampsia (n=63), fetal growth restriction (n=27), and gestational hypertension (n=23). We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p,P=0.037,P=0.009; miR-517*,P=0.033,P=0.043; miR-520a*,P=0.001,P=0.009; miR-525,P=0.026,P=0.01; miR-526a,P=0.03,P=0.035) were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.
Synthesis, Spectroscopic Characterisation, and Biopotential and DNA Cleavage Applications of Mixed Ligand 4‐N,N‐Dimethylaminopyridine Metal Complexes
Authors: Dilip C. Surendra , Manikandan K. , Subahashini D. Rajalaxmi (a) , Thiruneelakandan R.
Published: November 2013

The mixed ligand transition metal complexes of 4‐N,N‐dimethylaminopyridine (DP) and chloride as primary and secondary ligands with the general formula [M(DP)3Cl3]; M = Cr(III) and Fe(III); [M′(DP)4Cl2]M′ = Co(II), Ni(II), Cu(II), and Cd(II) were synthesized in a microwave oven. The complexes were characterized by FT‐IR and UV, 1HNMR, 13CNMR spectra, TG/DTG, and various physicoanalytical techniques. From the magnetic moment measurements and the electronic spectral data, a distorted octahedral geometry was proposed for the complexes. The complexes express similar trend of thermal behaviour such that they lose water of hydration initially with the subsequent emission of organic and inorganic fragments and leave left the metal oxides as residue. The activation thermodynamic parameters, such as E*, ΔH*, ΔS*, and ΔG* of the metal complexes, illustrate the spontaneous formation of the complexes. The antimicrobial studies against various pathogenic bacterial and fungal serums insist on that the enhanced potential of the complexes over their ligand and their biopotential properties increases with concentration. The DNA interaction of the synthesized complexes on CT‐DNA was investigated by UV‐Vis spectroscopy, viscosity, thermal denaturation, and electroanalytical experiments and their binding constants (Kb) were also calculated.
Link-Based Signalized Arterial Progression Optimization with Practical Travel Speed
Authors: Xianyu Wu , Peifeng Hu , Zhenzhou Yuan
Published: November 2013

Bandwidth is defined as the maximum amount of green time for a designated movement as it passes through an arterial. In most previous studies, bandwidth has been referred to arterial bandwidth. In practice, a balance between link bandwidth and arterial bandwidth has proven to be important in optimizing coordinated signal timing plans, because not all drivers need to pass through all the intersections on an arterial. This study proposes an algorithm on how to obtain an optimal coordinated signal timing plan with both optimal link bandwidth and optimal arterial bandwidth considering practical vehicles’ speed. The weighted link bandwidth attainability is introduced as an additional measure of effectiveness for assessing the optimization results. The link bandwidth optimization is built based on the improvement of Messer’s algorithm about bandwidth optimization. The arterial bandwidth optimization algorithm takes into consideration the weighted link bandwidth attainability while selecting phase sequences. The proposed algorithm is demonstrated in a case study, and many improvements are archived when a balanced consideration is given to both link bandwidth and arterial bandwidth. Fine-tuning of initial signal timing plan is done using practical travel speed. The evaluation results show a rather significant improvement which is achieved.
Is the Oxidative DNA Damage Level of Human Lymphocyte Correlated with the Antioxidant Capacity of Serum or the Base Excision Repair Activity of Lymphocyte?
Authors: Tsai Yi-Chih , Li Pei-Yi , Chen Chung-Chu , Liu Yin-Chang
Published: November 2013

A random screening of human blood samples from 24 individuals of nonsmoker was conducted to examine the correlation between the oxidative DNA damage level of lymphocytes and the antioxidant capacity of serum or the base excision repair (BER) activity of lymphocytes. The oxidative DNA damage level was measured with comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated with a modified comet assay including nuclear extract of lymphocytes for enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent antioxidant capacity assay. We found that though the endogenous DNA oxidation levels varied among the individuals, each individual level appeared to be steady for at least 1 month. Our results indicate that the oxidative DNA damage level is insignificantly or weakly correlated with antioxidant capacity or BER activity, respectively. However, lymphocytes from carriers ofHelicobacter pylori(HP) orHepatitis B virus(HBV) tend to give higher levels of oxidative DNA damage (P<0.05). Though sera of this group of individuals show no particular tendency with reduced antioxidant capacity, the respective BER activities of lymphocytes are lower in average (P<0.05). Thus, reduction of repair activity may be associated with the genotoxic effect of HP or HBV infection.
Feasibility Study of Stress Measurement in Prestressing Tendons Using Villari Effect and Induced Magnetic Field
Authors: Joh Changbin , Lee Jung Woo , Kwahk Imjong
Published: November 2013

This paper investigates experimentally the feasibility of estimating the stress in the prestressing tendons of prestressed concrete bridges using the magnetic field induced by an electromagnet and the Villari effect in which the magnetic susceptibility or permeability of a ferromagnetic material changes when subjected to a mechanical stress. The test results show the good linearity between the stress in the prestressing tendon and the induced magnetic flux density within the practical stress range of the tendons. In addition, the induced magnetic flux density in the tendon appears to depend on the intensity of the electromagnet and the distance between the electromagnet and the tendon regardless of the concrete cover. Accordingly, although further studies are needed for practical applications, the stress in the prestressing tendon of a prestressed concrete bridge can be estimated by measuring the induced magnetic flux density generated in the tendon and by using the linear relationship between this induced magnetic flux density and the stress in the prestressing tendon.
On Analytical Methods in Neuroblastoma Detection
Authors: Martínez-Díaz R. , Balaguer J. , Sánchez Ruiz L. M. , Bello P. , Castel V. , Perís-Fajarnés G.
Published: November 2013

Nonlinear dynamics of cancer recurrence are known to be governed by several factors as initial tumour size, number of metastatic sites, or quantity of drug resistant cells. The precise extent and location of tumours are very important factors so quantitative and consistent methods of evaluation are needed to assess reponse to patient therapy. Whole-bodyI123-metaiodobenzylguanidine (mIBG) scintigraphy is used as primary medical image modality to detect neuroblastoma tumours due to its high specificity and sensitivity. However, current oncological guidelines are based on qualitative observer-dependent analysis. This fact makes it difficult to compare results of scintigraphies taken at different moments during therapy or at different institutions. In this paper, we review analytical methods used in neuroblastoma detection and propose an observer-independent method to quantitatively analyse aI123-mIBG scintigraphy.
Some New Generalized Difference Spaces of Nonabsolute Type Derived from the Spaces ℓp and ℓ∞
Authors: Başar Feyzi , Karaisa Ali
Published: November 2013

We introduce the sequence space of none absolute type which is a p‐normed space and BK space in the cases 0 < p < 1 and 1 ⩽ p ⩽ ∞, respectively, and prove that and ℓp are linearly isomorphic for 0 < p ⩽ ∞. Furthermore, we give some inclusion relations concerning the space and we construct the basis for the space , where 1 ⩽ p < ∞. Furthermore, we determine the alpha‐, beta‐ and gamma‐duals of the space for 1 ⩽ p ⩽ ∞. Finally, we investigate some geometric properties concerning Banach‐Saks type p and give Gurarii′s modulus of convexity for the normed space .
Management of Extramammary Paget's Disease: A Case Report and Review of the Literature
Authors: Guerra Rosa , Misra Subhasis
Published: November 2013

Extramammary Paget's Disease (EMPD) is a rare condition of the skin that often involves the vulva, perianal region, scrotum, penis, and axilla. Although prognosis is generally favorable, it can be associated with neoplasms of the bladder, urethra, prostate, and rectum. This report presents a case of scrotal EMPD that failed treatment with imiquimod 5% cream and discusses benefits and complications of available treatment options. The variation of treatment success emphasizes the importance of further research.
Systems Biology Profiling of AMD on the Basis of Gene Expression
Authors: Abu-Asab Mones S. , Salazar Jose , Tuo Jingsheng , Chan Chi-Chao
Published: November 2013

Genetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and the correlations of AMD’s genotypes, phenotypes, and disease spectrum are still awaiting resolution. We are tackling both problems with systems biology phylogenetic parsimony analysis. Gene expression data (GSE29801: NCBI, Geo) of macular and extramacular specimens of the retinas and retinal pigment epithelium (RPE) choroid complexes representing dry AMD without geographic atrophy (GA), choroidal neovascularization (CNV), GA, as well as pre-AMD and subclinical pre-AMD were polarized against their respective normal specimens and then processed through the parsimony program MIX to produce phylogenetic cladograms. Gene lists from cladograms’ nodes were processed in Genomatix GePS to reveal the affected signaling pathway networks. Cladograms exposed a highly heterogeneous transcriptomic profiles within all the conventional phenotypes. Moreover, clades and nodal synapomorphies did not support the classical AMD phenotypes as valid transcriptomal genotypes. Gene lists defined by cladogram nodes showed that the AMD-related deregulations occurring in the neural retina were different from those in RPE-choroidal tissue. Our analysis suggests a more complex transcriptional profile of the phenotypes than expected. Evaluation of the disease in much earlier stages is needed to elucidate the initial events of AMD.
Conjugated Heat and Mass Transfer in Convective Drying in Compact Wood Kilns: A System Approach
Authors: Vaz M. , Zdanski P. S. B. , Cerqueira R. F. , Possamai D. G.
Published: November 2013

Drying is a required operation in timber manufacturing industries. Most drying processes utilise convective kilns, which involve coupling between transient heat and mass (moisture content) transfer in solids and convection in a flowing medium. In the present work, the flow field in the kiln is determined using a system approach based on a general head loss equation, whereas the coupling between transient heat and mass transfer in the timber is accomplished by a solution of a local differential model across the timber stack. The scheme is applied to study the effects of distinct geometric kiln configurations and air flow temperatures upon drying rates and moisture content.
Laboratory Diagnosis of Human Rabies: Recent Advances
Authors: Mani Reeta Subramaniam , Madhusudana Shampur Narayan
Published: November 2013

Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre‐ or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future.
A pH-Sensitive, Biobased Calcium Carbonate Aragonite Nanocrystal as a Novel Anticancer Delivery System
Authors: Shafiu Kamba Abdullahi , Ismail Maznah , Tengku Ibrahim Tengku Azmi , Zakaria Zuki Abu Bakar
Published: November 2013

The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells.In vitrochemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO3nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
Slip-Flow and Heat Transfer in a Porous Microchannel Saturated with Power-Law Fluid
Authors: Taamneh Yazan , Omari Reyad
Published: November 2013

This study aims to numerically examine the fluid flow and heat transfer in a porous microchannel saturated with power-law fluid. The governing momentum and energy equations are solved by using the finite difference technique. The present study focuses on the slip flow regime, and the flow in porous media is modeled using the modified Darcy-Brinkman-Forchheimer model for power-law fluids. Parametric studies are conducted to examine the effects of Knudsen number, Darcy number, power law index, and inertia parameter. Results are given in terms of skin friction and Nusselt number. It is found that when the Knudsen number and the power law index decrease, the skin friction on the walls decreases. This effect is reduced slowly while the Darcy number decreases until it reaches the Darcy regime. Consequently, with a very low permeability the effect of power law index vanishes. The numerical results indicated also that when the power law index decreases the fully-developed Nusselt number increases considerably especially, in the limit of high permeability, that is, nonDarcy regime. As far as Darcy regime is concerned the effects of the Knudsen number and the power law index of the fully-developed Nusselt number is very little.
Robust Adaptive Control for Nonlinear Discrete-Time Systems by Using Multiple Models
Authors: Li Xiao-Li , Liu De-Xin , Li Jiang-Yun , Ding Da-Wei
Published: November 2013

Back propagation (BP) neural network is used to approximate the dynamic character of nonlinear discrete-time system. Considering the unmodeling dynamics of the system, the weights of neural network are updated by using a dead-zone algorithm and a robust adaptive controller based on the BP neural network is proposed. For the situation that jumping change parameters exist, multiple neural networks with multiple weights are built to cover the uncertainty of parameters, and multiple controllers based on these models are set up. At every sample time, a performance index function based on the identification error will be used to choose the optimal model and the corresponding controller. Different kinds of combinations of fixed model and adaptive model will be used for robust multiple models adaptive control (MMAC). The proof of stability and convergence of MMAC are given, and the significant efficacy of the proposed methods is tested by simulation.
On Parametric Gevrey Asymptotics for Singularly Perturbed Partial Differential Equations with Delays
Authors: Lastra Alberto , Malek Stéphane
Published: November 2013

We study a family of singularly perturbed -difference-differential equations in the complex domain. We provide sectorial holomorphic solutions in the perturbation parameter . Moreover, we achieve the existence of a common formal power series in which represents each actual solution and establish -Gevrey estimates involved in this representation. The proof of the main result rests on a new version of the so-called Malgrange-Sibuya theorem regarding -Gevrey asymptotics. A particular Dirichlet like series is studied on the way.