bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giardia duodenalis Arginine Deiminase Modulates the Phenotype and Cytokine Secretion of Human Dendritic Cells by Depletion of Arginine and Formation of Ammonia
Authors: Banik Stefanie , Renner Viveros Pablo , Seeber Frank , Klotz Christian , Ignatius Ralf , Aebischer Toni 
Published: April 2013

ABSTRACT

Depletion of arginine is a recognized strategy that pathogens use to evade immune effector mechanisms. Depletion depends on microbial enzymes such as arginases, which are considered virulence factors. The effect is mostly interpreted as being a consequence of successful competition with host enzymes for the substrate. However, both arginases and arginine deiminases (ADI) have been associated with pathogen virulence. Both deplete arginine, but their reaction products differ. An ADI has been implicated in the virulence of
Giardia duodenalis
, an intestinal parasite that infects humans and animals, causing significant morbidity. Dendritic cells (DC) play a critical role in host defense and also in a murine
G. duodenalis
infection model. The functional properties of these innate immune cells depend on the milieu in which they are activated. Here, the dependence of the response of these cells on arginine was studied by using
Giardia
ADI and lipopolysaccharide-stimulated human monocyte-derived DC. Arginine depletion by ADI significantly increased tumor necrosis factor alpha and decreased interleukin-10 (IL-10) and IL-12p40 secretion. It also reduced the upregulation of surface CD83 and CD86 molecules, which are involved in cell-cell interactions. Arginine depletion also reduced the phosphorylation of S6 kinase in DC, suggesting the involvement of the mammalian target of rapamycin signaling pathway. The changes were due to arginine depletion and the formation of reaction products, in particular, ammonium ions. Comparison of NH
4
+
and urea revealed distinct immunomodulatory activities of these products of deiminases and arginases, respectively. The data suggest that a better understanding of the role of arginine-depleting pathogen enzymes for immune evasion will have to take enzyme class and reaction products into consideration.
Phase I Dose-Escalation Study of VB-111, an Antiangiogenic Virotherapy, in Patients with Advanced Solid Tumors
Authors: Brenner Andrew J. , Cohen Yael C. , Breitbart Eyal , Bangio Livnat , Sarantopoulos John , Giles Francis J. , Borden Ernest C. , Harats Dror , Triozzi Pierre L. 
Published: April 2013

Abstract
Purpose: VB-111 is an antiangiogenic agent consisting of a nonreplicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a Fas-chimera transgene in angiogenic endothelial cells. In a phase I dose-escalation study, pharmacokinetics, pharmacodynamics, safety, and efficacy of a single dose of VB-111 in patients with advanced solid tumors were evaluated.
Experimental Design: VB-111 was administered as a single i.v. infusion at escalating doses from 1 × 1010 (cohort 1) to 1 × 1013 (cohort 7) viral particles (VP) in successive cohorts. Assessments included pharmacokinetic and pharmacodynamic profiles, tumor response, and overall survival.
Results: Thirty-three patients were enrolled. VB-111 was safe and well-tolerated; self-limited fever and chills were seen at doses above 3 × 1011 VPs. Transgene expression was not detected in blood but was detected in an aspirate from a subcutaneous metastasis after treatment. One patient with papillary thyroid carcinoma had a partial response.
Conclusions: VB-111 was safe and well tolerated in patients with advanced metastatic cancer at a single administration of up to 1 × 1013 VPs. Evidence of transgene expression in tumor tissue and tumor response was observed. Clin Cancer Res; 19(14); 3996–4007. ©2013 AACR.
Inhibition of Melanoma Growth by Small Molecules That Promote the Mitochondrial Localization of ATF2
Authors: Varsano Tal , Lau Eric , Feng Yongmei , Garrido Marine , Milan Loribelle , Heynen-Genel Susanne , Hassig Christian A. , Ronai Ze'ev A. 
Published: April 2013

Abstract
Purpose: Effective therapy for malignant melanoma, the leading cause of death from skin cancer, remains an area of significant unmet need in oncology. The elevated expression of PKCϵ in advanced metastatic melanoma results in the increased phosphorylation of the transcription factor ATF2 on threonine 52, which causes its nuclear localization and confers its oncogenic activities. The nuclear-to-mitochondrial translocation of ATF2 following genotoxic stress promotes apoptosis, a function that is largely lost in melanoma cells, due to its confined nuclear localization. Therefore, promoting the nuclear export of ATF2, which sensitizes melanoma cells to apoptosis, represents a novel therapeutic modality.
Experimental Design: We conducted a pilot high-throughput screen of 3,800 compounds to identify small molecules that promote melanoma cell death by inducing the cytoplasmic localization of ATF2. The imaging-based ATF2 translocation assay was conducted using UACC903 melanoma cells that stably express doxycycline-inducible GFP-ATF2.
Results: We identified two compounds (SBI-0089410 and SBI-0087702) that promoted the cytoplasmic localization of ATF2, reduced cell viability, inhibited colony formation, cell motility, and anchorage-free growth, and increased mitochondrial membrane permeability. SBI-0089410 inhibited the 12-O-tetradecanoylphorbol-l3-acetate (TPA)–induced membrane translocation of protein kinase C (PKC) isoforms, whereas both compounds decreased ATF2 phosphorylation by PKCϵ and ATF2 transcriptional activity. Overexpression of either constitutively active PKCϵ or phosphomimic mutant ATF2T52E attenuated the cellular effects of the compounds.
Conclusion: The imaging-based high-throughput screen provides a proof-of-concept for the identification of small molecules that block the oncogenic addiction to PKCϵ signaling by promoting ATF2 nuclear export, resulting in mitochondrial membrane leakage and melanoma cell death. Clin Cancer Res; 19(10); 2710–22. ©2013 AACR.
Electrocardiographic Studies of Romidepsin Demonstrate Its Safety and Identify a Potential Role for KATP Channel
Authors: Noonan Anne M. , Eisch Robin A. , Liewehr David J. , Sissung Tristan M. , Venzon David J. , Flagg Thomas P. , Haigney Mark C. , Steinberg Seth M. , Figg William D. , Piekarz Richard L. , Bates Susan E. 
Published: April 2013

Abstract
Purpose: Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted.
Experimental Design: A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy.
Results: Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of KATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes.
Conclusions: We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin. Clin Cancer Res; 19(11); 3095–104. ©2013 AACR.
Primary Prevention of Sudden Cardiac Death in a Nonischemic Dilated Cardiomyopathy Population
Authors: Gatzoulis Konstantinos A. , Vouliotis Apostolos-Ilias , Tsiachris Dimitris , Salourou Maria , Archontakis Stefanos , Dilaveris Polychronis , Gialernios Theodoros , Arsenos Petros , Karystinos Georgios , Sideris Skevos , Kallikazaros Ioannis , Stefanadis Christodoulos 
Published: April 2013

Background—
We considered the role of programmed ventricular stimulation in primary prevention of sudden cardiac death in an idiopathic dilated cardiomyopathy population.

Methods and Results—

One hundred fifty-eight patients with idiopathic dilated cardiomyopathy underwent programmed ventricular stimulation. Ventricular tachycardia/ventricular fibrillation was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II), where ventricular tachycardia/ventricular fibrillation was not induced. Sixty-nine patients with idiopathic dilated cardiomyopathy underwent implantable cardioverter-defibrillator (ICD) implantation: 41/44 in group I and 28/114 in group II. The major end points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the 2 groups. Patients with left ventricular ejection fraction ≤35% (n=119) demonstrated a higher overall mortality rate compared with the patients with left ventricular ejection fraction >35% (n=39; 16.8% versus 10.3%, log-rank
P
=0.025). Advanced New York Heart Association class (III and IV versus I and II) was the single independent and strongest prognostic factor of overall mortality (hazard ratio, 11.909;
P
<0.001; confidence interval, 3.106–45.65), as well as of cardiac mortality (hazard ratio, 14.787;
P
=0.001; confidence interval, 2.958–73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared with group II (30 of 41 patients–73.2% versus 5 of 28 patients–17.9%; log-rank
P
=0.001), either in the form of antitachycardia pacing (68.3% versus 17.9%; log-rank
P
=0.001) or in the shock delivery form (51.2% versus 17.9%; log-rank
P
=0.05). Induction of ventricular tachycardia/ventricular fibrillation during programmed ventricular stimulation in contrast to left ventricular ejection fraction was the single independent prognostic factor for future ICD activation (hazard ratio, 4.195;
P
=0.007; confidence interval, 1.467–11.994).

Conclusions—
Inducibility of ventricular tachycardia/ventricular fibrillation was associated with an increased likelihood of subsequent ICD activation and sudden cardiac death surrogate.
Radulphus Brito’s Commentary on Aristotle’s De anima
Authors: de Boer Sander W. 
Published: April 2013

Abstract
In 1974, Winfried Fauser published his edition of Radulphus Brito’s commentary on the third book of Aristotle’s De anima. This contribution continues his project by providing an edition of Brito’s commentary on the first book and the first third of the second book. An analysis of this part of the commentary shows that Brito developed some original views that had an impact on the fourteenth-century commentary tradition.
Calibration and Stability of Oxygen Sensors on Autonomous Floats
Authors: D'Asaro Eric A. , McNeil Craig 
Published: April 2013

Abstract
The calibration accuracy and stability of three Aanderaa 3835 optodes and three Sea-Bird Electronics SBE-43 oxygen sensors were evaluated over four years using in situ and laboratory calibrations. The sensors were mostly in storage, being in the ocean for typically only a few weeks per year and operated for only a few days per year. Both sensors measure partial pressure of oxygen, or equivalently saturation at standard pressure; results are expressed in this variable. It is assumed that sensor drift occurs in the oxygen sensitivity of the sensors, not the temperature compensation; this is well justified for the SBE-43 based on multiple calibrations. Neither sensor had significant long-term drift in output when sampling anoxic water. Sensor output at 100% saturation differed from the factory calibrations by up to ±6% (averaging −2.3% ± 3%) for the SBE-43 and up to −12.6% for the optodes. The optode output at 100% saturation is well described by a single decaying exponential with a decay constant of approximately 2 yr and an amplitude of 28%. The mechanism of this drift is unknown but is not primarily due to sensor operation. It may be different from that experienced by sensors continuously deployed in the ocean. Thus, although the optodes in this study did not have a stable calibration, their drift was stable and, once calibrated, allowed optode and SBE-43 pairs mounted on the same autonomous floats to be calibrated to an accuracy of ±0.4% over a 4-yr period.
Weighted kernel operators in variable exponent amalgam spaces
Authors: Kokilashvili Vakhtang , Meskhi Alexander , Zaighum Muhammad Asad 
Published: April 2013

Abstract
The paper is devoted to weighted inequalities for positive kernel operators in variable exponent amalgam spaces. In particular, a characterization of a weight v governing the boundedness/compactness of the weighted kernel operators

K
v

and

K
v

, defined on

R
+

and ℝ, respectively, under the log-Hölder continuity condition on exponents of spaces is established. These operators involve, for example, weighted variable parameter fractional integrals. The results are new even for constant exponent amalgam spaces.

MSC:46E30, 47B34.
Sufficient conditions for starlike functions associated with the lemniscate of Bernoulli
Authors: Kumar S Sivaprasad , Kumar Virendra , Ravichandran V , Cho Nak Eun 
Published: April 2013

Abstract
Let

−
1
≤
B
<
A
≤
1

. The condition on β is determined so that

1
+
β
z

p
′

(
z
)
/

p
k

(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

(

−
1
<
k
≤
3

) implies

p
(
z
)
≺

1
+
z

. Similarly, the condition on β is determined so that

1
+
β
z

p
′

(
z
)
/

p
n

(
z
)

or

p
(
z
)
+
β
z

p
′

(
z
)
/

p
n

(
z
)
≺

1
+
z

(

n
=
0
,
1
,
2

) implies

p
(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

or

1
+
z

. In addition to that, the condition on β is derived so that

p
(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

when

p
(
z
)
+
β
z

p
′

(
z
)
/
p
(
z
)
≺

1
+
z

. A few more problems of the similar flavor are also considered.

MSC:30C80, 30C45.
New bounds for Randic and GA indices
Authors: Lokesha V , Shetty B Shwetha , Ranjini PS , Cangul Ismail Naci , Cevik Ahmet Sinan 
Published: April 2013

Abstract
The main goal of this paper is to present some new lower and upper bounds for the Randic and GA indices in terms of Zagreb and modified Zagreb indices.

MSC: 05C05, 05C20, 05C90.
Cytological maps of lampbrush chromosomes of European water frogs (Pelophylax esculentuscomplex) from the Eastern Ukraine
Authors: Dedukh Dmitry , Mazepa Glib , Shabanov Dmitry , Rosanov Juriy , Litvinchuk Spartak , Borkin Leo , Saifitdinova Alsu , Krasikova Alla 
Published: April 2013

AbstractBackgroundHybridogenesis (hemiclonal inheritance) is a kind of clonal reproduction in which hybrids between parental species are reproduced by crossing with one of the parental species. European water frogs (Pelophylax esculentuscomplex) represent an appropriate model for studying interspecies hybridization, processes of hemiclonal inheritance and polyploidization.P. esculentuscomplex consists of two parental species,P. ridibundus(the lake frog) andP. lessonae(the pool frog), and their hybridogenetic hybrid –P. esculentus(the edible frog).Parental and hybrid frogs can reproduce syntopically and form hemiclonal population systems. For studying mechanisms underlying the maintenance of water frog population systems it is required to characterize the karyotypes transmitted in gametes of parental and different hybrid animals of both sexes.ResultsIn order to obtain an instrument for characterization of oocyte karyotypes in hybrid female frogs, we constructed cytological maps of lampbrush chromosomes from oocytes of both parental species originating in Eastern Ukraine. We further identified certain molecular components of chromosomal marker structures and mapped coilin-rich spheres and granules, chromosome associated nucleoli and special loops accumulating splicing factors. We recorded the dissimilarities betweenP. ridibundusandP. lessonaelampbrush chromosomes in the length of orthologous chromosomes, number and location of marker structures and interstitial (TTAGGG)n-repeat sites as well as activity of nucleolus organizer.Satellite repeat RrS1 was mapped in centromere regions of lampbrush chromosomes of the both species. Additionally, we discovered transcripts of RrS1 repeat in oocytes ofP. ridibundusandP. lessonae. Moreover, G-rich transcripts of telomere repeat were revealed in association with terminal regions ofP. ridibundusandP. lessonaelampbrush chromosomes.ConclusionsThe constructed cytological maps of lampbrush chromosomes ofP. ridibundusandP. lessonaeprovide basis to define the type of genome transmitted within individual oocytes ofP. esculentusfemales with different ploidy and from various population systems.
Long-range transcriptional regulation by the p110 CUX1 homeodomain protein on theENCODE array
Authors: Vadnais Charles , Awan Arif A , Harada Ryoko , Clermont Pier-Luc , Leduy Lam , Bérubé Ginette , Nepveu Alain 
Published: April 2013

Abstract

Background
Overexpression of the Cut homeobox 1 gene, CUX1, inverselycorrelates with patient survival in breast cancers. Cell-based assays andmolecular studies have revealed that transcriptional regulation byCUX1 involves mostly the proteolytically processed p110isoform. As there is no antibody specific to p110 CUX1 only, an alternatestrategy must be employed to identify its targets.

Results
We expressed physiological levels of a tagged-p110 CUX1 protein and performedchromatin affinity purification followed by hybridization on ENCODE andpromoter arrays. Targets were validated by chromatin immunoprecipitation andtranscriptional regulation by CUX1 was analyzed in expression profiling andRT-qPCR assays following CUX1 knockdown or p110 CUX1 overexpression.Approximately 47% and 14% of CUX1 binding sites were respectively mappedless than 4 Kbp, or more than 40 Kbp, away from a transcription start site.More genes exhibited changes in expression following CUX1 knockdown thanp110 CUX1 overexpression. CUX1 directly activated or repressed 7.4% and 8.4%of putative targets identified on the ENCODE and promoter arraysrespectively. This proportion increased to 11.2% for targets with 2 bindingsites or more. Transcriptional repression was observed in a slightly higherproportion of target genes. The CUX1 consensus binding motif, ATCRAT, wasfound at 47.2% of the CUX1 binding sites, yet only 8.3% of the CUX1consensus motifs present on the array were bound in vivo. Thepresence of a consensus binding motif did not have an impact on whether atarget gene was repressed or activated. Interestingly, the distance betweena binding site and a transcription start site did not significantly reducedthe ability of CUX1 to regulate a target gene. Moreover, CUX1 not only wasable to regulate the next adjacent gene, but also regulated the gene locatedbeyond this one as well as the gene located further away in the oppositedirection.

Conclusion
Our results demonstrate that p110 CUX1 can activate or repress transcriptionwhen bound at a distance and can regulate more than one gene on certaingenomic loci.
Cardiovascular fitness associated with cognitive performance in heart failure patients enrolled in cardiac rehabilitation
Authors: Garcia Sarah , Alosco Michael L , Spitznagel Mary Beth , Cohen Ronald , Raz Naftali , Sweet Lawrence , Josephson Richard , Hughes Joel , Rosneck Jim , Oberle Morgan L , Gunstad John 
Published: April 2013

AbstractBackgroundReduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population.MethodsForty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step test (2MST), and a series of medical history and self-report questionnaires.ResultsMaximum METs from stress testing demonstrated incremental predictive validity for attention (β = .41,p = .03), executive function (β = .37,p = .04), and memory domains (β = .46,p = .04). Partial correlations accounting for key medical and demographic characteristics revealed greater METs was associated with the 2MST (r(32) = .41,p = .02) but not with the Duke Activity Status Index (DASI) (r(32) = .24,p = .17).ConclusionThe current findings indicate that better fitness levels measured by METs is independently associated with better cognitive function in older adults with HF. Results also showed that METs was closely associated with one office-based measure of fitness (2MST), but not another (DASI). Prospective studies are needed to clarify the mechanisms linking fitness and cognitive function in HF.
Physical activity and its correlates in children: a cross-sectional study (the GINIplus & LISAplus studies)
Authors: Ortlieb Sandra , Schneider Gabriel , Koletzko Sibylle , Berdel Dietrich , von Berg Andrea , Bauer Carl-Peter , Schaaf Beate , Herbarth Olf , Lehmann Irina , Hoffmann Barbara , Heinrich Joachim , Schulz Holger ,   GINIplus and LISAplus Study Groups
Published: April 2013

Abstract

Background
Physical inactivity among children is an increasing problem that adversely affects children’s health. A better understanding of factors which affect physical activity (PA) will help create effective interventions aimed at raising the activity levels of children. This cross-sectional study examined the associations of PA with individual (biological, social, behavioral, psychological) and environmental (East vs. West Germany, rural vs. urban regions) characteristics in children.

Methods
Information on PA and potential correlates was collected from 1843 girls and 1997 boys using questionnaires during the 10-year follow-up of two prospective birth cohort studies (GINIplus and LISAplus). Study regions represent urban and rural sites as well as East and West of Germany. Logistic regression modeling was applied to examine cross-sectional associations between individual as well as environmental factors and PA levels.

Results
Five of fourteen variables were significantly associated with PA. Among children aged 10, girls tended to be less active than boys, especially with respect to vigorous PA (OR = 0.72 for summer). Children who were not a member of a sports club showed a substantially reduced amount of PA in winter (OR = 0.15). Rural environments promote moderate PA, particularly in winter (OR = 1.88), whereas an increased time outdoors primarily promotes moderate PA in summer (OR = 12.41). Children with abnormal emotional symptoms exhibited reduced physical activity, particularly in winter (OR = 0.60). BMI, puberty, parental BMI, parental education, household income, siblings, TV/PC consumption, and method of arriving school, were not associated with PA.

Conclusions
When considering correlates of PA from several domains simultaneously, only few factors (sex, sports club membership, physical environment, time outdoors, and emotional symptoms) appear to be relevant. Although the causality needs to be ascertained in longitudinal studies, variables which cannot be modified should be used to identify risk groups while modifiable variables, such as sports club activities, may be addressed in intervention programs.