bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminazene Protects Corpus Cavernosum Against Hypercholesterolemia-Induced Injury
Authors: Fraga-Silva Rodrigo A. , Costa-Fraga Fabiana P. , Montecucco Fabrizio , Sturny Mikael , Faye Younoss , Mach François , Pelli Graziano , Shenoy Vinayak , da Silva Rafaela F. , Raizada Mohan K. , Santos Robson A.S. , Stergiopulos Nikolaos 
Published: November 2014

Abstract

Introduction
Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin angiotensin system, which breaks down angiotensin II and forms angiotensin-(1–7). In erectile tissues, it has been documented that angiotensin II contributes to the development of erectile dysfunction (ED), while treatment with angiotensin-(1–7) improves penile erection. However, the expression and function of ACE2 in erectile tissues have never been investigated.

Aim
Here, we examined the expression of ACE2 in erectile tissues and its actions against hypercholesterolemia-induced corpus cavernosum (CC) injury.

Methods
Hypercholesterolemic apolipoprotein E knockout (ApoE−/−) mice, a well-known model of ED, were treated with diminazene aceturate (DIZE), an ACE2 activator compound, or vehicle for 3 weeks. Reactive oxygen species (ROS), collagen content, and protein expression of ACE2, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) subunits were evaluated in the penis of DIZE-treated and untreated ApoE−/− mice. Functional studies were performed in CC strips.

Main Outcome Measures
ACE2 expression and its role in modulating nitric oxide (NO)/ROS production and fibrosis within the CC of hypercholesterolemic mice were the main outcome measures.

Results
ACE2 was expressed in smooth muscle and endothelial cells of mouse CC. Interestingly, ACE2 was downregulated in penis of hypercholesterolemic mice with ED, suggesting a protective role of ACE2 on the CC homeostasis. In accordance with that, pharmacological ACE2 activation by DIZE treatment reduced ROS production and NADPH oxidase expression, and elevated nNOS and eNOS expression and NO bioavailability in the penis of ApoE−/− mice. Additionally, DIZE decreased collagen content within the CC. These beneficial actions of DIZE on the CC were not accompanied by improvements in atherosclerotic plaque size or serum lipid profile.

Conclusion
ACE2 is expressed in erectile tissue and its reduction is associated with hypercholesterolemia-induced ED. Additionally, treatment with DIZE improved hypercholesterolemia-induced CC injury, suggesting ACE2 as a potential target for treating ED.
Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture
Authors: Plessers E. , Watteyn A. , Wyns H. , Pardon B. , De Baere S. , De Backer P. , Croubels S. 
Published: November 2014

The pharmacokinetic properties of ketoprofen were determined in 4‐week‐old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(−) and S(+) enantiomer were quantified separately, using a stereospecificHPLC‐UVassay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(−) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration–time curve (AUC0→∞) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(−) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(−) enantiomer, respectively) and a lower apparent volume of distribution (Vd/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(−) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.
Seed production temperature regulation of primary dormancy occurs through control of seed coat phenylpropanoid metabolism
Authors: MacGregor Dana R. , Kendall Sarah L. , Florance Hannah , Fedi Fabio , Moore Karen , Paszkiewicz Konrad , Smirnoff Nicholas , Penfield Steven 
Published: November 2014

Summary

Environmental changes during seed production are important drivers of lot‐to‐lot variation in seed behaviour and enable wild species to time their life history with seasonal cues. Temperature during seed set is the dominant environmental signal determining the depth of primary dormancy, although the mechanisms though which temperature changes impart changes in dormancy state are still only partly understood.

We used molecular, genetic and biochemical techniques to examine the mechanism through which temperature variation affects Arabidopsis thaliana seed dormancy.

Here we show that, in Arabidopsis, low temperatures during seed maturation result in an increase in phenylpropanoid gene expression in seeds and that this correlates with higher concentrations of seed coat procyanidins. Lower maturation temperatures cause differences in coat permeability to tetrazolium, and mutants with increased seed coat permeability and/or low procyanidin concentrations are less able to enter strongly dormant states after exposure to low temperatures during seed maturation.

Our data show that maternal temperature signalling regulates seed coat properties, and this is an important pathway through which the environmental signals control primary dormancy depth.
Monitoring depth of anesthesia: from consciousness to nociception. A window on subcortical brain activity
Authors: Constant Isabelle , Sabourdin Nada 
Published: November 2014

SummaryAnesthesia results from several inhibitor processes, which interact to lead to loss of consciousness, amnesia, immobility, and analgesia. The anesthetic agents act on the whole brain, the cortical and subcortical areas according to their receptor targets. The conscious processes are rather integrated at the level of the cortical neuronal network, while the nonconscious processes such as the nociception or implicit memory require subcortical processing. A reliable and meaningful monitoring of depth of anesthesia should provide assessment of these different processes. Besides the EEG monitoring which gives mainly information on cortical anesthetic effects, it would be relevant to have also a subcortical feedback allowing an assessment of nociception. Several devices have been proposed in this last decade, to give us an idea of the analgesia/nociception balance. Up to now, most of them are based on the assessment of the autonomic response to noxious stimulation. Among the emerging clinical devices, we can mention those which assess vascular sympathetic response (skin conductance), cardiac and vascular sympathetic response (surgical pleth index), parasympathetic cardiac response (analgesia nociception index), and finally the pupillometry which is based on the assessment of the pupillary reflex dilatation induced by nociceptive stimulations. Basically, the skin conductance might be the most adapted to assess the stress in the awake or sedated neonate, while the performances of this method appear disappointing under anesthesia. The surgical pleth index is still poorly investigated in children. The analgesia nociception index showed promising results in adults, which have to be confirmed, especially in children and in infants, and lastly pupillometry, which can be considered as reliable and reactive in children as in adults, but which is still sometimes complicated in its use.
Modelling the influence of land‐use changes on biophysical and biochemical interactions at regional and global scales
Authors: DEVARAJU N. , BALA G. , NEMANI R. 
Published: November 2014

AbstractLand‐use changes since the start of the industrial era account for nearly one‐third of the cumulative anthropogenic CO2 emissions. In addition to the greenhouse effect of CO2 emissions, changes in land use also affect climate via changes in surface physical properties such as albedo, evapotranspiration and roughness length. Recent modelling studies suggest that these biophysical components may be comparable with biochemical effects. In regard to climate change, the effects of these two distinct processes may counterbalance one another both regionally and, possibly, globally. In this article, through hypothetical large‐scale deforestation simulations using a global climate model, we contrast the implications of afforestation on ameliorating or enhancing anthropogenic contributions from previously converted (agricultural) land surfaces. Based on our review of past studies on this subject, we conclude that the sum of both biophysical and biochemical effects should be assessed when large‐scale afforestation is used for countering global warming, and the net effect on global mean temperature change depends on the location of deforestation/afforestation. Further, although biochemical effects trigger global climate change, biophysical effects often cause strong local and regional climate change. The implication of the biophysical effects for adaptation and mitigation of climate change in agriculture and agroforestry sectors is discussed.
Molecular Epidemiology of Rotavirus in Cats in the United Kingdom
Authors: German A. C. , Iturriza-Gómara M. , Dove W. , Sandrasegaram M. , Nakagomi T. , Nakagomi O. , Cunliffe N. , Radford A. D. , Morgan K. L. 
Published: November 2014

ABSTRACT

Rotaviruses are leading causes of gastroenteritis in the young of many species. Molecular epidemiological studies in children suggest that interspecies transmission contributes to rotavirus strain diversity in people. However, population-based studies of rotaviruses in animals are few. We investigated the prevalence, risk factors for infection, and genetic diversity of rotavirus A in a cross-sectional survey of cats housed within 25 rescue catteries across the United Kingdom. Morning litter tray fecal samples were collected during the winter and summer in 2012 from all pens containing kittens and a random sample of those housing adult cats. Group A rotavirus RNA was detected by real-time reverse transcription-PCR, and positive samples were G and P genotyped using nested VP4 and VP7 PCR assays. A total of 1,727 fecal samples were collected from 1,105 pens. Overall, the prevalence of rotavirus was 3.0% (95% confidence interval [CI], 1.2 to 4.9%). Thirteen out of 25 (52%; 95% CI, 31.3 to 72.2%) centers housed at least one rotavirus-positive cat. The prevalence of rotavirus was associated with season (odds ratio, 14.8 [95% CI, 1.1 to 200.4];
P
= 0.04) but not age or diarrhea. It was higher during the summer (4.7%; 95% CI, 1.2 to 8.3%) than in winter (0.8%; 95% CI, 0.2 to 1.5%). Asymptomatic epidemics of infection were detected in two centers. G genotypes were characterized for 19 (33.3%) of the 57 rotavirus-positive samples and P genotypes for 36 (59.7%). Two rotavirus genotypes were identified, G3P[9] and G6P[9]. This is the first population-based study of rotavirus in cats and the first report of feline G6P[9], which questions the previous belief that G6P[9] in people is of bovine origin.
Global Displacement of Canine Parvovirus by a Host-Adapted Variant: Structural Comparison between Pandemic Viruses with Distinct Host Ranges
Authors: Organtini Lindsey J. , Allison Andrew B. , Lukk Tiit , Parrish Colin R. , Hafenstein Susan 
Published: November 2014

ABSTRACT
Canine parvovirus type 2 (CPV-2) emerged in 1978 and spread worldwide within 2 years. Subsequently, CPV-2 was completely replaced by the variant CPV-2a, which is characterized by four specific capsid (VP2) mutations. The X-ray crystal structure of the CPV-2a capsid shows that each mutation confers small local changes. The loss of a hydrogen bond and introduction of a glycine residue likely introduce flexibility to sites that control interactions with the host receptor, antibodies, and sialic acids.
Cellular Differentiation Regulator BLIMP1 Induces Epstein-Barr Virus Lytic Reactivation in Epithelial and B Cells by Activating Transcription from both the R and Z Promoters
Authors: Reusch Jessica A. , Nawandar Dhananjay M. , Wright Kenneth L. , Kenney Shannon C. , Mertz Janet E. 
Published: November 2014

ABSTRACT

Epstein-Barr virus (EBV) maintains a lifelong latent infection within a subset of its host's memory B cells, while lytic EBV replication takes place in plasma cells and differentiated epithelial cells. Therefore, cellular transcription factors, such as BLIMP1, that are key mediators of differentiation likely contribute to the EBV latent-to-lytic switch. Previous reports showed that ectopic BLIMP1 expression induces reactivation in some EBV-positive (EBV
+
) B-cell lines and transcription from Zp, with all Z
+
cells in oral hairy leukoplakia being BLIMP1
+
. Here, we examined BLIMP1's role in inducing EBV lytic gene expression in numerous EBV
+
epithelial and B-cell lines and activating transcription from Rp. BLIMP1 addition was sufficient to induce reactivation in latently infected epithelial cells derived from gastric cancers, nasopharyngeal carcinomas, and normal oral keratinocytes (NOK) as well as some, but not all B-cell lines. BLIMP1 strongly induced transcription from Rp as well as Zp, with there being three or more synergistically acting BLIMP1-responsive elements (BRE) within Rp. BLIMP1's DNA-binding domain was required for reactivation, but BLIMP1 did not directly bind the nucleotide (nt) −660 Rp BRE. siRNA knockdown of BLIMP1 inhibited 12-
O
-tetradecanoyl-phorbol-13-acetate (TPA)-induced lytic reactivation in NOK-Akata cells, cells that can be reactivated by R, but not Z. Thus, we conclude that BLIMP1 expression is both necessary and sufficient to induce EBV lytic replication in many (possibly all) EBV
+
epithelial-cell types, but in only a subset of EBV
+
B-cell types; it does so, at least in part, by strongly activating expression of both EBV immediately early genes,
BZLF1
and
BRLF1
.

IMPORTANCE
This study is the first one to show that the cellular transcription factor BLIMP1, a key player in both epithelial and B-cell differentiation, induces reactivation of the oncogenic herpesvirus Epstein-Barr virus (EBV) out of latency into lytic replication in a variety of cancerous epithelial cell types as well as in some, but not all, B-cell types that contain this virus in a dormant state. The mechanism by which BLIMP1 does so involves strongly turning on expression of both of the immediate early genes of the virus, probably by directly acting upon the promoters as part of protein complexes or indirectly by altering the expression or activities of some cellular transcription factors and signaling pathways. The fact that EBV
+
cancers usually contain mostly undifferentiated cells may be due in part to these cells dying from lytic EBV infection when they differentiate and express wild-type BLIMP1.
GBF1- and ACBD3-Independent Recruitment of PI4KIIIβ to Replication Sites by Rhinovirus 3A Proteins
Authors: Dorobantu Cristina M. , Ford-Siltz Lauren A. , Sittig Simone P. , Lanke Kjerstin H. W. , Belov George A. , van Kuppeveld Frank J. M. , van der Schaar Hilde M. 
Published: November 2014

ABSTRACT
PI4KIIIβ recruitment to Golgi membranes relies on GBF1/Arf and ACBD3. Enteroviruses such as poliovirus and coxsackievirus recruit PI4KIIIβ to their replication sites via their 3A proteins. Here, we show that human rhinovirus (HRV) 3A also recruited PI4KIIIβ to replication sites. Unlike other enterovirus 3A proteins, HRV 3A failed to bind GBF1. Although HRV 3A was previously shown to interact with ACBD3, our data suggest that PI4KIIIβ recruitment occurred independently of both GBF1 and ACBD3.
The Inherent Premise of Immunotherapy for Cancer Dormancy
Authors: Manjili Masoud H. 
Published: November 2014

AbstractClinical cancer dormancy is evident from the detection of circulating tumor cells in the blood and tissue-residing disseminated tumor cells in the bone marrow of cancer survivors who have been clinically disease free. Emerging evidence from clinical and preclinical studies suggests that tumor dormancy is a critical step in the development of both primary cancer and advanced-stage disease. In this review, it is shown that (i) naturally occurring tumor dormancy precedes occurrence of primary cancer, and (ii) conventional cancer therapies result in treatment-induced tumor dormancy, which in turn could lead to distant recurrence of cancer or permanent tumor dormancy, depending on immunogenic status of dormancy. Given that cellular dormancy is an evolutionary conserved survival mechanism in biologic systems, any stress or cytotoxic therapy could trigger cellular dormancy. Therefore, a successful cancer therapy is likely to be achieved by establishing permanent tumor dormancy and preventing distant recurrence of cancer or by eliminating dormant tumor cells. This could be accomplished by cancer immunotherapy because of the establishment of long-term memory responses. Cancer Res; 74(23); 6745–9. ©2014 AACR.
Intellectual-Human Rights Defenders and Claims for Academic Freedom under Human Rights Law
Authors: Quinn Robert , Levine Jesse 
Published: November 2014

Human rights claims arising out of attacks on intellectual-human rights defenders (hrds), if brought, typically do not include claims for violations of academic freedom. As a result the standards are underdeveloped relative to other human rights claims and the scope of academic freedom violations globally. This may be in part due to a negatively reinforcing lack of familiarity with issues of academic freedom and the available standards for protection among human rights advocates, and in part to the fact that attacks on academic freedom often manifest as violations of other rights under which claims are brought (e.g. wrongful detention or torture). This article argues that existing human rights law would sustain claims for violations of academic freedom as independently and interdependently derived from the rights to freedom of opinion and expression and the right to education. The article argues that including academic freedom claims in such cases has the benefit of providing an additional basis for relief while strengthening the claim for relief on a manifested violation by providing evidence of motive and intent. Including academic freedom claims also has the independent value of addressing the wider harms to the claimant-victim and society that result from attacks on intellectual expression and are not reached by relief on the manifested violation alone, including harms to a claimant-victim’s creative, intellectual or expressive work, and widespread chilling effects on creativity, teaching, publication and the free exchange of ideas in society.
A Theoretical Study on the Spontaneous Radiation of Inertia–Gravity Waves Using the Renormalization Group Method. Part I: Derivation of the Renormalization Group Equations
Authors: Yasuda Yuki , Sato Kaoru , Sugimoto Norihiko 
Published: November 2014

Abstract
By using the renormalization group (RG) method, the interaction between balanced flows and Doppler-shifted inertia–gravity waves (GWs) is formulated for the hydrostatic Boussinesq equations on the f plane. The derived time-evolution equations [RG equations (RGEs)] describe the spontaneous GW radiation from the components slaved to the vortical flow through the quasi resonance, together with the GW radiation reaction on the large-scale flow. The quasi resonance occurs when the space–time scales of GWs are partially comparable to those of slaved components. This theory treats a coexistence system with slow time scales composed of GWs significantly Doppler-shifted by the vortical flow and the balanced flow that interact with each other. The theory includes five dependent variables having slow time scales: one slow variable (linear potential vorticity), two Doppler-shifted fast ones (GW components), and two diagnostic fast ones. Each fast component consists of horizontal divergence and ageostrophic vorticity. The spontaneously radiated GWs are regarded as superpositions of the GW components obtained as low-frequency eigenmodes of the fast variables in a given vortical flow. Slowly varying nonlinear terms of the fast variables are included as the diagnostic components, which are the sum of the slaved components and the GW radiation reactions. A comparison of the balanced adjustment equation (BAE) by Plougonven and Zhang with the linearized RGE shows that the RGE is formally reduced to the BAE by ignoring the GW radiation reaction, although the interpretation on the GW radiation mechanism is significantly different; GWs are radiated through the quasi resonance with a balanced flow because of the time-scale matching.
A Theoretical Study on the Spontaneous Radiation of Inertia–Gravity Waves Using the Renormalization Group Method. Part II: Verification of the Theoretical Equations by Numerical Simulation
Authors: Yasuda Yuki , Sato Kaoru , Sugimoto Norihiko 
Published: November 2014

Abstract
The renormalization group equations (RGEs) describing spontaneous inertia–gravity wave (GW) radiation from part of a balanced flow through a quasi resonance that were derived in a companion paper by Yasuda et al. are validated through numerical simulations of the vortex dipole using the Japan Meteorological Agency nonhydrostatic model (JMA-NHM). The RGEs are integrated for two vortical flow fields: the first is the initial condition that does not contain GWs used for the JMA-NHM simulations, and the second is the simulated thirtieth-day field by the JMA-NHM. The theoretically obtained GW distributions in both RGE integrations are consistent with the numerical simulations using the JMA-NHM. This result supports the validity of the RGE theory. GW radiation in the dipole is physically interpreted either as the mountain-wave-like mechanism proposed by McIntyre or as the velocity-variation mechanism proposed by Viúdez. The shear of the large-scale flow likely determines which mechanism is dominant. In addition, the distribution of GW momentum fluxes is examined based on the JMA-NHM simulation data. The GWs propagating upward from the jet have negative momentum fluxes, while those propagating downward have positive ones. The magnitude of momentum fluxes is approximately proportional to the sixth power of the Rossby number between 0.15 and 0.4.
Oxidative Stress Regulates IL‐4 Gene Expression in Mast Cells through the Reduction of Histone Deacetylase
Authors: Nakamaru Yuji , Takagi Dai , Homma Akihiro , Hatakeyama Shigetsugu , Fukuda Satoshi 
Published: November 2014

ObjectiveMany proinflammatory cytokines are regulated by the acetylation and deacetylation of the core histone. Since dysregulation of T helper 2 cytokine production is a key in the pathogenesis of allergic diseases, we examined the role of histone deacetylase (HDAC) on interleukin (IL)–4 gene expression in mast cells. We also examined whether oxidative stress has any impact on HDAC activity.Study DesignIn vitro study.SettingAcademic research laboratory.MethodsAn IgE‐sensitized mast cell line (RBL‐2H3 cells) was treated with varying concentrations of the HDAC inhibitors trichostatin A (TSA) and H2O2 and stimulated with antigens. The amount of IL‐4 gene expression was quantified by real‐time polymerase chain reaction. Quantitative measurement of IL‐4 in the cell supernatant was performed using enzyme‐linked immunosorbent assay. Moreover, HDAC activity was measured with the use of a nonisotopic assay that utilized an HDAC Fluorescent Activity Assay Kit.ResultsIL‐4 mRNA expression was induced by antigens in IgE‐sensitized RBL‐2H3 cells. Pretreatment with TSA and H2O2 enhanced IL‐4 mRNA expression up to 5‐fold in a dose‐dependent manner. Furthermore, HDAC activity in RBL‐2H3 cells was reduced after treatment with H2O2.ConclusionOur results suggest that oxidative stress may up‐regulate IL‐4 gene expression in mast cells via a decrease in HDAC activity.