bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Al-doped ZnO thin films prepared in Ar + H2 atmosphere and their vacuum annealing behavior
Authors: Zhu Bailin , Lü Kun , Wang Jun , Li Taotao , Wu Jun , Zeng Dawen , Xie Changsheng
Published: September 2013

The microstructure and electrical–optical properties of Al-doped ZnO (AZO) films have been studied as a function of H2 flux in the magnetron sputtering process at 150 °C and postannealing temperature in vacuum. As H2 flux increases in the sputtering gas, the AZO films deposited have a (002) preferred orientation rather than the mixed (100) and (002) orientations, the grain size shows a tendency to first increase then decrease, and (002) diffraction peak position is inclined to shift to higher angles first then to lower angles. The resistivity of the films first decreases then increases with H2 flux, and the lowest resistivity of 4.02 × 10−4 Ω cm is obtained at a H2 flux of 10 sccm. The average transmittance in the visible region shows little dependence on H2 flux. As a whole, the AZO films with higher values of figure of merit are obtained when the H2 flux is in the range of 6–12 sccm. The AZO films deposited in Ar and Ar + H2 exhibit different annealing behaviors. For the AZO film deposited in Ar, the grain size gradually increases, the stresses are relaxed, the resistivity first decreases then increases, and the average transmittance in the visible region is unchanged initially then somewhat decreased as annealing temperature is increased. The optimum annealing temperature for improving properties of AZO films deposited in Ar is 300 °C. For the AZO films deposited in Ar + H2, annealing does not significantly change the microstructure but increases the resistivity of the films; the average transmittance in the visible region remains unchanged initially but greatly reduced with further increase in annealing temperature. The carrier transport in the as-deposited and annealed films appears to be controlled by a mechanism of grain boundary scattering, and the value of Eg increases with the increase in carrier concentration due to Burstein–Moss effect.
Whole-Genome Sequences of Staphylococcus aureus ST398 Strains of Animal Origin
Authors: Hernandez David , van der Mee-Marquet Nathalie , Kluytmans Jan , Donnio Pierre-Yves , Quentin Roland , Corvaglia Anna-Rita , François Patrice
Published: September 2013

Staphylococcus aureus
sequence type 398 (ST398) was originally associated with animal infections. We announce the complete genome sequences of two ST398 methicillin-susceptible
S. aureus
strains from the livestock environment. These genome sequences assist in the characterization of interesting ST398 features relying on host tropism and epidemiological settings
.
Genome Sequences of Three hpAfrica2 Strains of Helicobacter pylori
Authors: Duncan Stacy S. , Bertoli M. Teresita , Kersulyte Dangeruta , Valk Pieter L. , Tamma Sravya , Segal Issy , McClain Mark S. , Cover Timothy L. , Berg Douglas E.
Published: September 2013

We present the genome sequences of three hpAfrica2 strains of
Helicobacter pylori
, which are postulated to have evolved in isolation for many millennia in people of San ethnicity. Although previously considered to be ancestral to
Helicobacter acinonychis
, the hpAfrica2 strains differ markedly from
H. acinonychis
in their gene arrangement. These data provide new insights into
Helicobacter
evolution.
Whole-Genome Shotgun Sequencing of Rhodococcus erythropolis Strain P27, a Highly Radiation-Resistant Actinomycete from Antarctica
Authors: Gouvêa Taketani Rodrigo , Domingues Zucchi Tiago , Soares de Melo Itamar , Mendes Rodrigo
Published: September 2013

Here, we report the draft genome sequence of radiation-resistant
Rhodococcus erythropolis
strain P27, isolated from leaves of
Deschampsia antarctica
Desv. (
Poaceae
) in the Admiralty Bay area, Antarctica.
Genome Sequence of Lactobacillus fermentum Strain MTCC 8711, a Probiotic Bacterium Isolated from Yogurt
Authors: Jayashree Sathyanarayanan , Pooja Sharma , Pushpanathan Muthuirulan , Vishnu Udayakumar , Sankarasubramanian Jagadesan , Rajendhran Jeyaprakash , Gunasekaran Paramasamy
Published: September 2013

Lactobacillus fermentum
strain MTCC 8711 is a lactic acid bacterium isolated from yogurt. Here, we describe the draft genome sequence and annotation of this strain. The 2,566,297-bp-long genome consisted of a single chromosome and seven plasmids. The genome contains 2,609 protein-coding and 74 RNA genes.
Draft Genome Sequence of Exopolysaccharide-Producing Thermophilic Bacterium Brevibacillus thermoruber Strain 423
Authors: Yasar Yildiz Songul , Kambourova Margarita , Arga Kazim Yalcin , Toksoy Oner Ebru
Published: September 2013

Brevibacillus thermoruber
strain 423 is a Gram-positive, spore-forming, aerobic, and thermophilic bacterium that produces mannogalactoglucan exopolysaccharide (EPS). We report the draft genome sequence of
B. thermoruber
423, which will accelerate research on the cellular organization of thermophilic bacteria, as well as the rational design and optimization of EPS production.
Complete Genome Sequence of Staphylococcus aureus 6850, a Highly Cytotoxic and Clinically Virulent Methicillin-Sensitive Strain with Distant Relatedness to Prototype Strains
Authors: Fraunholz Martin , Bernhardt Jörg , Schuldes Jörg , Daniel Rolf , Hecker Michael , Sinha Bhanu
Published: September 2013

Staphylococcus aureus
is a frequent human commensal bacterium and pathogen. Here we report the complete genome sequence of strain 6850 (
spa
type t185; sequence type 50 [ST50]), a highly cytotoxic and clinically virulent methicillin-sensitive strain from a patient with complicated
S. aureus
bacteremia associated with osteomyelitis and septic arthritis.
Protocol for a randomised controlled trial: efficacy of donepezil against psychosis in Parkinson's disease (EDAP)
Authors: Sawada Hideyuki , Oeda Tomoko
Published: September 2013

Introduction

Psychosis, including hallucinations and delusions, is one of the important non-motor problems in patients with Parkinson's disease (PD) and is possibly associated with cholinergic neuronal degeneration. The EDAP (Efficacy of Donepezil against Psychosis in PD) study will evaluate the efficacy of donepezil, a brain acetylcholine esterase inhibitor, for prevention of psychosis in PD.

Methods and analysis

Psychosis is assessed every 4 weeks using the Parkinson Psychosis Questionnaire (PPQ) and patients with PD whose PPQ-B score (hallucinations) and PPQ-C score (delusions) have been zero for 8 weeks before enrolment are randomised to two arms: patients receiving donepezil hydrochloride or patients receiving placebo. The patients are then followed for 96 weeks. The primary outcome measure is the time to the event, defined as getting 2 points or more on the PPQ-B score or PPQ-C score, which is assessed using a survival time analysis. The hypothesis being tested is that donepezil prevents psychosis in patients with PD. Efficacy will be tested statistically using the intention-to-treat analysis including a log-rank test or Cox proportional hazard models. Secondary outcomes, such as changes of PPQ scores and Unified Parkinson's Disease Rating Scale scores from baseline will be assessed.

Ethics and dissemination

Ethics approval was received from the Central Review Board of the National Hospital Organization, Tokyo, Japan. The trial was declared and registered to the Pharmaceuticals and Medical Devices Agency(PMDA), Japan (No. 22-4018). All participants will receive a written informed consent that was approved by the Central Review. A completed written informed consent is required to enrol in the study. Severe adverse events will be monitored by investigators and in cases where a severe adverse event was previously unreported, it will be reported to the PMDA.

Clinical Trial Registration Number

UMIN000005403.
Physical activity during pregnancy and offspring cardiovascular risk factors: findings from a prospective cohort study
Authors: Millard Louise A C , Lawlor Debbie A , Fraser Abigail , Howe Laura D
Published: September 2013

Objectives

The long-term consequences of maternal physical activity during pregnancy for offspring cardiovascular health are unknown. We examined the association of maternal self-reported physical activity in pregnancy (18 weeks gestation) with offspring cardiovascular risk factors at age 15.

Design

Prospective cohort study.

Setting

The Avon Longitudinal Study of Parents and Children (ALSPAC).

Participants

4665 maternal-offspring pairs (based on a sample with multiple imputation to deal with missing data) from the ALSPAC, a prospective cohort based in the South West of England with mothers recruited in pregnancy in 1991–1992.

Primary and secondary outcome measures

Offspring cardiovascular risk factors at age 15; body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, glucose, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides.

Results

Greater maternal physical activity was associated with lower BMI, waist circumference, glucose and insulin in unadjusted analyses. The magnitude of associations was generally small with wide CIs, and most associations attenuated towards the null after adjusting for confounders. The strongest evidence of association after adjustment for confounders was for glucose, although the 95% CI for this association includes the null; a one SD greater physical activity during pregnancy was associated with a −0.013 mmol/L difference in offspring glucose levels (equivalent to approximately one-third of a SD; 95% CI −0.027 to 0.001 mmol/L).

Conclusions

Our results suggest that maternal physical activity in pregnancy, measured at 18 weeks gestation, is unlikely to be an important determinant of later offspring cardiovascular health. There was some suggestion of association with offspring glucose, but given that all other associations (including insulin) were null after adjustment for confounders, this result should be interpreted with caution.
Initial non-participation and loss to follow-up in a Danish youth cohort: implications for relative risk estimates
Authors: Winding Trine N , Andersen Johan H , Labriola Merete , Nohr Ellen A
Published: September 2013

Background

Initial non-participation and loss to follow-up in the Danish youth cohort Vestliv could introduce selection bias of the measured risk estimates.

Objective

To investigate the impact of initial non-participation and loss to follow-up on the validity of descriptive measures and selected estimates of relative risk.

Methods

Of the 3681 young people defining the source population, 83% answered a questionnaire at baseline in 2004. At follow-up waves in 2007 and 2010, the response rates were 71% and 64%, respectively. Relative ORs (RORs) were used to examine the impact of initial non-participation and loss to follow-up on the association between socioeconomic or personal risk factors at age 14/15 and educational attainment at age 20/21. RORs were calculated as OR (baseline population)/OR (source population) or OR (follow-up population)/OR (baseline population).

Results

The participants had slightly better school abilities and came more often from homes with two adults, higher income or higher educational level. These differences increased at subsequent follow-ups. The effect of initial non-participation on the ORs was modest with most RORs being close to one. Loss to follow-up led to larger variations in the RORs ranging from 0.77 to 1.62 although for most estimates, the bias was minor. None of the measured RORs were statistically different from one indicating no significant bias.

Conclusions

Although certain characteristics were related to those who initially chose to participate and especially to those who participated at follow-ups, it did not have any large influence on the relative risk estimates measured in the study.
Contribution of sexual practices (other than anal sex) to bacterial sexually transmitted infection transmission in men who have sex with men: a cross-sectional analysis using electronic health records
Authors: Nash Jessica L , Hocking Jane S , Read Tim R H , Chen Marcus Y , Bradshaw Catriona S , Forcey Dana S , Fairley Christopher K
Published: September 2013

Objective

We quantified the proportion of cases and risk of primary syphilis (PS), urethral chlamydia (UCT) and urethral gonorrhoea (UGC) attributable to sexual practices other than anal sex.

Methods

In this cross-sectional study, electronic records for men who have sex with men (MSM) who attended the Melbourne Sexual Health Centre between July 2002 (for PS) or January 2006 (for UCT and UGC) and October 2012, inclusive, were examined.

Results

There were 37 533 eligible consultations; 2374 (6%) of these reported no anal sex. There were 204 PS diagnoses, 673 UCT diagnoses, and 618 UGC diagnoses; 12 (6%), 16 (2%) and 44 (7%) cases, respectively, occurred in consultations where no anal sex was reported in the previous 3 months (PS, UGC) or twelve months (UCT). Among MSM reporting no anal sex, PS was diagnosed in 0.5 cases/100 consultations, UCT was diagnosed in 1.5 cases/100 tests for UCT and UGC was diagnosed in 14 cases/100 tests for UGC. UCT was significantly more common in MSM reporting anal sex (OR 2.18, 95% CI 1.32 to 3.59, p=0.002), but PS (OR 1.07 95% CI 0.6 to 1.93, p=0.82) and UGC (OR 1.28 95% CI 0.92 to 1.79. p=0.14) were not. For MSM reporting anal sex, condom use was protective for all three infections (all p≤0.03).

Conclusions

Our findings suggest that UCT uncommonly occurs from sexual practices other than anal sex; however, these practices contribute significantly to PS and UGC. Successful programmes to control PS and UGC will need strategies, such as frequent testing, in addition to promoting condom use.
UNDERLYING LOGICS THAT TRANSFORM SURVIVAL OR SUBSISTENT ENTREPRENEURSHIP CLUSTERS IN DEVELOPING COUNTRIES
Authors: HE XIAOHONG , CHI RENYONG
Published: September 2013

Poor entrepreneurs in developing countries are trapped at subsistence level. This study attempts to understand how survival entrepreneurial clusters can evolve into innovative industrial networks. By conceptualizing survival entrepreneurship cluster evolution, this research focuses on alternative binary paths of either the advance or decline at each juncture of cluster evolutionary trajectory and identifies factors that determine evolution direction. The conceptual model is further developed as it applied to a cluster case in China. This study suggests which mechanisms and factors allow a cluster to adapt, to avoid stagnation, decline, or death, and to rejuvenate at each transformational juncture.
Connectivity estimation between turbiditic channels and overbank deposits from the modelling of an outcrop analogue (Pab Formation, Maastrichtian, Pakistan)
Authors: Eschard R. , Deschamps R. , Doligez B. , Lerat O. , Langlais V. , Euzen T.
Published: September 2013

The facies associations of the overflow deposits associated with turbidite channels were studied in the outcrops of the Maastrichtian Pab Sandstone, in SW Pakistan. In this area, a basin-floor fan was preserved from the platform to the deep basin setting. In the mid-fan setting, a channel complex crops out in three dimensions, and consists of a dozen channels and their overflow deposits, including levees, crevasse lobes and spill-over lobes. The overbank deposits can be directly in contact with the channel-fill, but, in many cases, matrix-supported debris-flow deposits made lenses close to the channel base. Heterolithic drapes of thin-bedded turbidite deposits were also preserved along the channel margins. A three-dimensional (3D) static model describing the heterogeneity distribution within the turbiditic channel complex was compiled using both stochastic and deterministic approaches in a site where two channels were laterally connected by overbank deposits. Petro-acoustic properties derived from a subsurface database were then assigned to the facies to perform seismic simulations. The synthetic seismic simulations showed that the channel base can easily be misinterpreted compared to the geological model. Dynamic modelling, such as well test and streamline simulations, was also performed using the model to assess the transition between the channel and overbank deposits from a dynamic point of view. As a result of the streamline simulations, the overbank deposits connecting the channel homogenized the pressure regime in the reservoir. However, the sweeping efficiency of water injection can be affected by the heterogeneity distribution along the channel margins. A significant volume of oil could also be by-passed because of the occurrence of early water breakthrough through the spill-over lobes, or because the flow slowed down when it reached the heterogeneity along the channel margin.
Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum
Authors: Coon Steven D. , Schwartz John H. , Rajendran Vazhaikkurichi M. , Jepeal Lisa , Singh Satish K.
Published: September 2013

Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H+ gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H+:Gly-Sar cotransport on the apical membranes of mouse jejunum. H+:Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H+:Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum.
A 3-D mathematical model to identify organ-specific risks in rats during thermal stress
Authors: Rakesh Vineet , Stallings Jonathan D. , Helwig Bryan G. , Leon Lisa R. , Jackson David A. , Reifman Jaques
Published: September 2013

Early prediction of the adverse outcomes associated with heat stress is critical for effective management and mitigation of injury, which may sometimes lead to extreme undesirable clinical conditions, such as multiorgan dysfunction syndrome and death. Here, we developed a computational model to predict the spatiotemporal temperature distribution in a rat exposed to heat stress in an attempt to understand the correlation between heat load and differential organ dysfunction. The model includes a three-dimensional representation of the rat anatomy obtained from medical imaging and incorporates the key mechanisms of heat transfer during thermoregulation. We formulated a novel approach to estimate blood temperature by accounting for blood mixing from the different organs and to estimate the effects of the circadian rhythm in body temperature by considering day-night variations in metabolic heat generation and blood perfusion. We validated the model using in vivo core temperature measurements in control and heat-stressed rats and other published experimental data. The model predictions were within 1 SD of the measured data. The liver demonstrated the greatest susceptibility to heat stress, with the maximum temperature reaching 2°C higher than the measured core temperature and 95% of its volume exceeding the targeted experimental core temperature. Other organs also attained temperatures greater than the core temperature, illustrating the need to monitor multiple organs during heat stress. The model facilitates the identification of organ-specific risks during heat stress and has the potential to aid in the development of improved clinical strategies for thermal-injury prevention and management.
Photodynamic Therapy of Murine Mastocytoma Induces Specific Immune Responses against the Cancer/Testis Antigen P1A
Authors: Mroz Pawel , Vatansever Fatma , Muchowicz Angelika , Hamblin Michael R.
Published: September 2013

Photodynamic therapy (PDT) involves the intravenous administration of photosensitizers followed by illumination of the tumor with visible light, leading to local production of reactive oxygen species that cause vascular shutdown and tumor cell death. Antitumor immunity is stimulated after PDT because of the acute inflammatory response that involves activation of the innate immune system, leading to stimulation of adaptive immunity. We carried out PDT using benzoporphyrin derivative and 690-nm light after 15 minutes, in DBA/2 mice bearing either the mastocytoma, P815, which expresses the naturally occurring cancer/testis antigen P1A, or the corresponding tumor P1.204 that lacks P1A expression. Tumor cures, significantly higher survival, and rejection of tumor rechallenge were obtained with P815, which were not seen with P1.204 or seen with P815 growing in nude mice. Both CD4 and CD8 T cells had higher levels of intracellular cytokines when isolated from mice receiving PDT of P815 tumors than P1.204 tumors and CD8 T cells from P815-cured mice recognized the peptide epitope of the P1A antigen (LPYLGWLVF) using pentamer staining. Taken together, these findings show that PDT can induce a potent antigen- and epitope-specific immune response against a naturally occurring mouse tumor antigen. Cancer Res; 73(21); 6462–70. ©2013 AACR.
Targeting Plasminogen Activator Inhibitor-1 Inhibits Angiogenesis and Tumor Growth in a Human Cancer Xenograft Model
Authors: Gomes-Giacoia Evan , Miyake Makito , Goodison Steve , Rosser Charles J.
Published: September 2013

Cancers of the urinary bladder result in aggressive and highly angiogenic tumors for which standard treatments have only limited success. Patients with advanced disease have a 5-year survival rate of less than 20%, and no new anticancer agent has been successfully introduced into the clinic armamentarium for the treatment of bladder cancer in more than 20 years. Investigations have identified plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, as being highly expressed in several malignancies, including bladder cancer, in which high expression is associated with a poor prognosis. In this study, we evaluated PAI-1 as a potential therapeutic target for bladder cancer. PAI-1 expression was manipulated in a panel of cell lines and functional inhibition was achieved using the small molecule tiplaxtinin. Reduction or inhibition of PAI-1 resulted in the reduction of cellular proliferation, cell adhesion, and colony formation, and the induction of apoptosis and anoikis in vitro. Treatment of T24 xenografts with tiplaxtinin resulted in inhibition of angiogenesis and induction of apoptosis, leading to a significant reduction in tumor growth. Similar results were obtained through evaluation of the human cervical cancer HeLa cell line, showing that PAI-1–mediated effects are not restricted to tumor cells of bladder origin. Collectively, these data show that targeting PAI-1 may be beneficial and support the notion that novel drugs such as tiplaxtinin could be investigated as anticancer agents. Mol Cancer Ther; 12(12); 2697–708. ©2013 AACR.
A Novel Combinatorial Nanotechnology-Based Oral Chemopreventive Regimen Demonstrates Significant Suppression of Pancreatic Cancer Neoplastic Lesions
Authors: Grandhi B. Karthik , Thakkar Arvind , Wang Jeffrey , Prabhu Sunil
Published: September 2013

Pancreatic cancer is a deadly disease killing 37,000 Americans each year. Despite two decades of research on treatment options, the chances of survival are still less than 5% upon diagnosis. Recently, chemopreventive strategies have gained considerable attention as an alternative to treatment. We have previously shown significant in vitro chemopreventive effects with low-dose combinations of aspirin, curcumin, and sulforaphane (ACS) on pancreatic cancer cell lines. Here, we report the results of 24-week chemopreventive study with the oral administration of ACS combinations on the N-nitrosobis (2-oxopropyl) amine (BOP)-treated Syrian golden hamster model to suppress the progression of pancreatic intraepithelial neoplasms (PanIN) using unmodified (free drug) combinations of ACS, and nanoencapsulated (solid lipid nanoparticles; SLN) combinations of aspirin, curcumin, and free sulforaphane. The use of three different doses (low, medium, and high) of unmodified ACS combinations exhibited reduction in tumor incidence by 18%, 50%, and 68.7% respectively; whereas the modified nanoencapsulated ACS regimens reduced tumor incidence by 33%, 67%, and 75%, respectively, at 10 times lower dose compared with the free drug combinations. Similarly, although the unmodified free ACS showed a notable reduction in cell proliferation, the SLN encapsulated ACS regimens showed significant reduction in cell proliferation at 6.3%, 58.6%, and 72.8% as evidenced by proliferating cell nuclear antigen expression. Cell apoptotic indices were also upregulated by 1.5, 2.8, and 3.2 times, respectively, compared with BOP control. These studies provide a proof-of-concept for the use of an oral, low-dose, nanotechnology-based combinatorial regimen for the long-term chemoprevention of pancreatic cancer. Cancer Prev Res; 6(10); 1015–25. ©2013 AACR.
ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry
Authors: Karreth Florian A. , Pandolfi Pier Paolo
Published: September 2013

The cancer transcriptome is characterized by aberrant expression of both protein-coding and noncoding transcripts. Similar to mRNAs, a significant portion of the noncoding transcriptome, including long noncoding RNAs and pseudogenes, harbors microRNA (miRNA)-response elements (MRE). The recent discovery of competitive endogenous RNAs (ceRNA), natural decoys that compete for a common pool of miRNAs, provides a framework to systematically functionalize MRE-harboring noncoding RNAs and integrate them with the protein-coding RNA dimension in complex ceRNA networks. Functional interactions in ceRNA networks aid in coordinating a number of biologic processes and, when perturbed, contribute to disease pathogenesis. In this review, we discuss recent discoveries that implicate natural miRNA decoys in the development of cancer.

Significance: Cross-talk between ceRNAs through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of diseases such as cancer. As cross-talk can be predicted on the basis of the overlap of miRNA-binding sites, we are now one step closer to a complete functionalization of the human transcriptome, especially the noncoding space. Cancer Discov; 3(10); 1113–21. ©2013 AACR.
Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL
Authors: Aspord Caroline , Leccia Marie-Therese , Charles Julie , Plumas Joel
Published: September 2013

Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13- and IL-10–producing T cells in patients with melanoma correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities. Cancer Immunol Res; 1(6); 402–15. ©2013 AACR.
Interface between Pharmacotherapy and Genes in Human Obesity
Authors: O'Connor Annalouise , Swick Andrew G.
Published: September 2013

Obesity is a polygenic chronic condition, and dysregulation in multiple underlying energy balance processes drives the obese phenotype. Lifestyle changes can be difficult to sustain long term, and anti-obesity drugs can be an advantageous component of a successful weight loss plan. However, due to lack of efficacy or adverse safety profiles, there is currently a limited selection of anti-obesity drugs on the market. This, coupled with the notable interindividual variability in efficacy of approved treatments, represents a significant unmet medical need. In this review, we will highlight this variability in weight loss response to these existing anti-obesity compounds and discuss how underpinning genetic variation is associated with weight loss outcomes. Existing research in the field of pharmacogenomics and obesity drugs will be highlighted, as will possibilities for future focus. We will conclude by exploring examples of successful pharmacogenomics studies, and also by asking how pharmacogenomics can be built into the drug development pipeline for the benefit of patients and pharmaceutical companies alike.
Risk Factors of γ-Hydroxybutyrate Overdosing
Authors: Korf Dirk J. , Nabben Ton , Benschop Annemieke , Ribbink Kim , van Amsterdam Jan G.C.
Published: September 2013

The aim of this study was to identify in recreational drug users the factors which increase the risk of overdosing (OD) with γ-hydroxybutyrate (GHB). A purposive sample of 45 experienced GHB users was interviewed, equally divided into three groups (never OD, occasional OD, and repeat OD). The repeat OD group scored highest on many risk factors regarding GHB use, the occasional OD group scored intermediate, and the never OD group scored lowest. Participants, whether or not they had overdosed on GHB, most often perceived GHB use (e.g. using more GHB than usual, using GHB doses too closely together) as the main reason for GHB OD, and many participants who had overdosed on GHB reported that they had taken more GHB than usual at their most recent occasion of GHB OD. No significant differences in co-use of GHB with other substances were found between the three groups. Our findings indicate that using GHB in the company of groups of friends probably reduces, but does not eliminate, the risk of OD.
Twenty Years of Physical Mapping of Major Ribosomal RNA Genes across the Teleosts: A Review of Research
Authors: Gornung E.
Published: September 2013

Molecular cytogenetic data on the number and position of 45S ribosomal RNA genes (rDNA; located in nucleolus organizing regions, NORs) detected by FISH in 330 species of 77 families and 22 orders of bony fishes (Teleostei) and, additionally, 11 species of basal ray-finned fishes are compiled and analyzed. The portion of species with single rDNA sites in the sample amounts to 72%. The percentage of species with multiple NORs decreases with increasing numbers of rDNA loci per genome, i.e. scarcely 3% of species carry 4 or more rDNA-bearing chromosome pairs. 43% of all rDNA sites analyzed occur terminally on the short arms of chromosomes or constitute them. In general, terminal rDNA sites account for 87% of all examined cases. Interspecific variation in the location of single rDNA sites among related taxa, polymorphisms of multiple NORs in some groups of teleosts and analytical outcomes on the subject are reviewed.
Assessment of Adjuvant Trastuzumab-Associated Cardiac Toxicity in Korean Patients with Breast Cancer: A Single-Center Analysis
Authors: Cha Chihwan , Ahn Sung Gwe , Lee Hak Min , Lee Hak Woo , Lee Seung Ah , Jeong Joon
Published: September 2013

Background: We performed this analysis to investigate the clinical presentation of trastuzumab-associated cardiac toxicity in Korean women. Method: 124 patients treated in a single institute from January 2006 to November 2011 with adjuvant trastuzumab therapy following primary surgery were identified from a database. We evaluated the cumulative incidence of cardiac toxicity, associated risk factors, and changes in cardiac function during trastuzumab treatment. Results: The median age of patients was 50 years (range 27-73). After 12 months of follow-up, the cumulative incidence of cardiac toxicity was 12.1% (grade I: 8.1%, grade II: 0.8%, grade III: 3.2%). In total, 4% of patients discontinued treatment due to cardiac dysfunction. The left ventricular ejection fraction (LVEF) recovered in all patients who discontinued or delayed treatment due to cardiac dysfunction following treatment discontinuation. The degree of the decrease in LVEF was large at 6 months after the initiation of treatment. A lower LVEF at baseline (<65%) was associated with cardiac toxicity. Conclusions: The low incidence of cardiac toxicity and the reversibility of cardiac dysfunction may validate the safety of trastuzumab treatment in Korean women with an acceptable baseline LVEF.
Assessment of Problematic Internet Use by the Compulsive Internet Use Scale and the Internet Addiction Test: A Sample of Problematic and Pathological Gamblers
Authors: Guertler Diana , Rumpf Hans-Juergen , Bischof Anja , Kastirke Nadin , Petersen Kay Uwe , John Ulrich , Meyer Christian
Published: September 2013

This study aims to analyze psychometric properties and validity of the Compulsive Internet Use Scale (CIUS) and the Internet Addiction Test (IAT) and, second, to determine a threshold for the CIUS which matches the IAT cut-off for detecting problematic Internet use. A total of 292 subjects with problematic or pathological gambling (237 men, 55 women) aged 14-63 years and with private Internet use for at least 1 h per working or weekend day were recruited via different recruitment channels. Results include that both scales were internally consistent (Cronbach's α = 0.9) and had satisfactory convergent validity (r = 0.75; 95% CI 0.70-0.80). The correlation with duration of private Internet use per week was significantly higher for the CIUS (r = 0.54) compared to the IAT (r = 0.40). Among all participants, 25.3% were classified as problematic Internet users based on the IAT with a cut-off ≥40. The highest proportion of congruent classified cases results from a CIUS cut-off ≥18 (sensitivity 79.7%, specificity 79.4%). However, a higher cut-off (≥21) seems to be more appropriate for prevalence estimation of problematic Internet use.
Marked Retroperitoneal Lymphadenopathy in Hairy Cell Leukemia: A Case Report
Authors: Shackelford R.E. , Heldmann M. , Eskandari F. , Joshi N. , Browning J. , Maxwell N. , Coteligam J.
Published: September 2013

Hairy cell leukemia (HCL) is uncommonly associated with lymphadenopathy, while retroperitoneal lymphadenopathy is extremely uncommon. We report on a patient with a 12-year history of HCL who developed painless jaundice and ascites, accompanied by positional discomfort with persistent nausea. Computed tomography examination revealed 2 large retroperitoneal masses, which at autopsy consisted of HCL with focally intermixed pancreatic and peripancreatic tissue. Lymphadenopathy was not identified above the diaphragm or below the aortic bifurcation. No vasculitis or an unusual HCL histology was identified. As previous reports, our findings suggest that HCL with massive lymphadenopathy has a specific site predilection, but it is not necessarily accompanied by vasculitis or an unusual histology.
Angiogenic Impairment of the Vascular Endothelium
Authors: Palladino Mariangela , Gatto Ilaria , Neri Valentina , Straino Stefania , Smith Roy C. , Silver Marcy , Gaetani Eleonora , Marcantoni Margherita , Giarretta Igor , Stigliano Egidio , Capogrossi Maurizio , Hlatky Lynn , Landolfi Raffaele , Pola Roberto
Published: September 2013

Objective—

Dystrophin, the missing or defective protein in Duchenne muscular dystrophy, is expressed not only in muscle cells but also in vascular endothelial cells (ECs). In this study, we assessed the effects of dystrophin deficiency on the angiogenic capacities of ECs.

Approach and Results—

We isolated vascular ECs from
mdx
mice, the murine equivalent of Duchenne muscular dystrophy in humans, and wild-type controls, and we found that
mdx
-derived ECs have impaired angiogenic properties, in terms of migration, proliferation, and tube formation. They also undergo increased apoptosis in vitro compared with wild-type cells and have increased senescence-associated β-galactosidase activity.
Mdx
-derived ECs also display reduced ability to support myoblast proliferation when cocultured with satellite cell–derived primary myoblasts. These endothelial defects are mirrored by systemic impairment of angiogenesis in vivo, both on induction of ischemia, stimulation with growth factors in the corneal model and matrigel plug assays, and tumor growth. We also found that dystrophin forms a complex with endothelial NO synthase and caveolin-1 in ECs, and that NO production and cGMP formation are compromised in ECs isolated from
mdx
mice. Interestingly, treatment with aspirin enhances production of both cGMP and NO in dystrophic ECs, whereas low-dose aspirin improves the dystrophic phenotype of
mdx
mice in vivo, in terms of resistance to physical exercise, muscle fiber permeability, and capillary density.

Conclusions—

These findings demonstrate that impaired angiogenesis is a novel player and potential therapeutic target in Duchenne muscular dystrophy.
Serum 25-Hydroxyvitamin D Concentration in Subclinical Carotid Atherosclerosis
Authors: Deleskog Anna , Piksasova Olga , Silveira Angela , Gertow Karl , Baldassarre Damiano , Veglia Fabrizio , Sennblad Bengt , Strawbridge Rona J. , Larsson Malin , Leander Karin , Gigante Bruna , Kauhanen Jussi , Rauramaa Rainer , Smit Andries J. , Mannarino Elmo , Giral Philippe , Gustafsson Sven , Östenson Claes-Göran , Humphries Steve E. , Tremoli Elena , de Faire Ulf , Öhrvik John , Hamsten Anders
Published: September 2013

Objective—

Vitamin D deficiency has been implicated in cardiovascular disease and is associated with multiple cardiovascular risk factors. We investigated the serum 25-hydroxyvitamin D (25(OH)D) concentration in relation to latitude, baseline carotid intima-media thickness (IMT), and IMT progression, the carotid IMT measures being surrogate markers of subclinical atherosclerosis and cardiovascular disease risk.

Approach and Results—

Serum 25(OH)D concentration was related to high-resolution carotid IMT measures in 3430 middle-aged and elderly subjects with high cardiovascular risk but no prevalent disease, who were recruited at 7 centers in Finland, Sweden, The Netherlands, France, and Italy. Participants underwent carotid ultrasound examination at baseline and at months 15 and 30 after entry into the study, whereas blood samples, clinical data, and information about lifestyle were collected at baseline. Serum 25(OH)D levels were positively associated with latitude (Jonckheere–Terpstra χ=166.643;
P
<0.001) and, as previously reported, associated with a range of cardiovascular risk factors. There were no independent relationships between 25(OH)D and segment-specific or composite IMT measures in the entire cohort. In analyses stratified by sex, diabetes mellitus, and statin treatment, weak associations with some baseline and progression measures of carotid IMT were observed in males, diabetics, and nonstatin-treated individuals.

Conclusions—

Levels of 25(OH)D differed across Europe, were highest in the North, showed multiple associations with established and emerging cardiovascular risk factors but were not consistently, independently related to measures of carotid IMT. This argues against a protective role of vitamin D against subclinical atherosclerosis in high-risk individuals.
Bone Morphogenetic Proteins Protect Pulmonary Microvascular Endothelial Cells From Apoptosis by Upregulating α-B-Crystallin
Authors: Ciumas Mariana , Eyries Mélanie , Poirier Odette , Maugenre Svetlana , Dierick France , Gambaryan Natalia , Montagne Kevin , Nadaud Sophie , Soubrier Florent
Published: September 2013

Objective—

To investigate the role of bone morphogenetic proteins (BMPs) on α-B-crystallin (
CRYAB
) expression and its physiological consequences on endothelial cells (ECs).

Approach and Results—

We report that the gene encoding for the small heat shock protein,
CRYAB
, is a transcriptional target of the BMP signaling pathway. We demonstrate that
CRYAB
expression is upregulated strongly by BMPs in an EC line and in human lung microvascular ECs and human umbilical vein ECs. We show that BMP signals through the BMPR2-ALK1 pathway to upregulate
CRYAB
expression through a transcriptional indirect mechanism involving Id1. We observed that the known antiapoptotic effect of the BMPs is, in part, because of the upregulation of
CRYAB
expression in EC. We also show that
cryab
is downregulated in vivo, in a mouse model of pulmonary arterial hypertension induced by chronic hypoxia where the BMP pathway is downregulated.

Conclusions—

We demonstrate a cross-talk between BMPs and CRYAB and a major effect of this regulatory interaction on resistance to apoptosis.
High-Dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men
Authors: Dash Satya , Xiao Changting , Morgantini Cecilia , Szeto Linda , Lewis Gary F.
Published: September 2013

Objective—

Overproduction of hepatic apolipoprotein B (apoB)-100 containing very low-density lipoprotein particles and intestinal apoB-48 containing chylomicrons contributes to hypertriglyceridemia seen in conditions such as obesity and insulin resistance. Some, but not all, preclinical and clinical studies have demonstrated that the polyphenol resveratrol ameliorates insulin resistance and hypertriglyceridemia. Here, we assessed intestinal and hepatic lipoprotein turnover, in humans, after 2 weeks of treatment with resveratrol (1000 mg daily for week 1 followed by 2000 mg daily for week 2) or placebo.

Approach and Results—

Eight overweight or obese individuals with mild hypertriglyceridemia were studied on 2 occasions, 4 to 6 weeks apart, after treatment with resveratrol or placebo in a randomized, double-blinded, crossover study. Steady-state lipoprotein kinetics was assessed in a constant fed state with a primed, constant infusion of deuterated leucine. Resveratrol treatment did not significantly affect insulin sensitivity (homeostasis model of assessment of insulin resistance), fasting or fed plasma triglyceride concentration. Resveratrol reduced apoB-48 production rate by 22% (
P
=0.007) with no significant effect on fractional catabolic rate. Resveratrol reduced apoB-100 production rate by 27% (
P
=0.02) and fractional catabolic rate by 26% (
P
=0.04).

Conclusions—

These results indicate that 2 weeks of high-dose resveratrol reduces intestinal and hepatic lipoprotein particle production. Long-term studies are needed to evaluate the potential clinical benefits of resveratrol in patients with hypertriglyceridemia, who have increased concentrations of triglyceride-rich lipoprotein apoB-100 and apoB-48.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01451918.
Imaging Characteristics of Ischemic Strokes Related to Patent Foramen Ovale
Authors: Kim Bum Joon , Sohn Hoyon , Sun Byung Joo , Song Jae-Kwan , Kang Dong-Wha , Kim Jong S. , Kwon Sun U.
Published: September 2013

Background and Purpose—

Subclinical atrial fibrillation (AF) and patent foramen ovale (PFO) are the major causes of cryptogenic stroke, and neuroimaging may help distinguish the cause. We compared the imaging characteristics of ischemic stroke caused by PFO (PFO-stroke) and AF (AF-stroke).

Methods—

We recruited 117 patients with PFO-stroke and 358 patients with AF-stroke after excluding other causes. The lesion patterns were classified according to number, location, size, and pertinent vascular territory and were compared between the 2 groups. Occlusion of the corresponding artery and its recanalization rate were also investigated.

Results—

The lesion pattern of a PFO-stroke was more frequently observed as a single cortical infarction (34.2% versus 3.1%;
P
<0.001) or multiple small (<15 mm) scattered lesions (23.1% versus 5.9%;
P
<0.001) and in the vertebrobasilar artery territory (44.4% versus 22.9%;
P
<0.001). By contrast, AF-stroke was more frequently observed as a large cortico-subcortical infarction or confluent lesion (>15 mm) with additional lesions in multicirculatory territories. For a PFO-stroke, occlusion of the corresponding vessel on angiography was less frequent (34.2% versus 71.5%;
P
<0.001), and the neurological deficit evaluated by the National Institutes of Health Stroke Scale was mild (3.48±4.16 versus 9.15±7.35;
P
<0.001). The recanalization rate was also lower (57.1% versus 78.3%;
P
=0.007).

Conclusions—

A PFO-stroke usually appears as a single cortical or multiple small ischemic lesions in the vertebrobasilar circulation without any visible vessel occlusion on angiography. The recanalization rate is significantly lower than in AF-stroke. These imaging characteristics of PFO-stroke may help to diagnose the mechanism and determine the treatment strategy.