bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
THRIVE Score Predicts Outcomes With a Third-Generation Endovascular Stroke Treatment Device in the TREVO-2 Trial
Authors: Flint Alexander C. , Xiang Bin , Gupta Rishi , Nogueira Raul G. , Lutsep Helmi L. , Jovin Tudor G. , Albers Gregory W. , Liebeskind David S. , Sanossian Nerses , Smith Wade S. 
Published: September 2013

Background and Purpose—
Several outcome prediction scores have been tested in patients receiving acute stroke treatment with previous generations of endovascular stroke treatment devices. The TREVO-2 trial was a randomized controlled trial comparing a novel endovascular stroke treatment device (the Trevo device) to a previous-generation endovascular stroke treatment device (the Merci device).

Methods—
We used data from the TREVO-2 trial to validate the Totaled Health Risks in Vascular Events (THRIVE) score in patients receiving treatment with a third-generation endovascular stroke treatment device and to compare THRIVE to other predictive scores. We used logistic regression to model outcomes and compared score performance with receiver operating characteristic curve analysis.

Results—
In the TREVO-2 trial, the THRIVE score strongly predicts clinical outcome and mortality. The relationship between THRIVE score and outcome is not influenced by either success of recanalization or the type of device used (Trevo versus Merci). The superiority of the Trevo device to the Merci device is evident particularly among patients with a low-to-moderate THRIVE score (0–5; 53.8% good outcome with Trevo versus 27.5% good outcome with Merci). In receiver operating characteristic curve analysis, the THRIVE score was comparable or superior to several other outcome prediction scores (HIAT, HIAT-2, SPAN-100, and iScore).

Conclusions—

The THRIVE score strongly predicts clinical outcome and mortality in the TREVO-2 trial. Taken together with THRIVE validation data from patients receiving intravenous tissue-type plasminogen activator or no acute treatment, the THRIVE score has broad predictive power in patients with acute ischemic stroke, which is likely because THRIVE reflects a set of strong nonmodifiable predictors of stroke outcome. A free Web calculator for the THRIVE score is available at
http://www.thrivescore.org
.
Does Use of the Recognition Of Stroke In the Emergency Room Stroke Assessment Tool Enhance Stroke Recognition by Ambulance Clinicians?
Authors: Fothergill Rachael T. , Williams Julia , Edwards Melanie J. , Russell Ian T. , Gompertz Patrick 
Published: September 2013

Background and Purpose—
UK ambulance services assess patients with suspected stroke using the Face Arm Speech Test (FAST). The Recognition Of Stroke In the Emergency Room (ROSIER) tool has been shown superior to the FAST in identifying strokes in emergency departments but has not previously been tested in the ambulance setting. We investigated whether ROSIER use by ambulance clinicians can improve stroke recognition.

Methods—
Ambulance clinicians used the ROSIER in place of the FAST to assess patients with suspected stroke. As the ROSIER includes all FAST elements, we calculated a FAST score from the ROSIER to enable comparisons between the two tools. Ambulance clinicians’ provisional stroke diagnoses using the ROSIER and calculated FAST were compared with stroke consultants’ diagnosis. We used stepwise logistic regression to compare the contribution of individual ROSIER and FAST items and patient demographics to the prediction of consultants’ diagnoses.

Results—
Sixty-four percent of strokes and 78% of nonstrokes identified by ambulance clinicians using the ROSIER were subsequently confirmed by a stroke consultant. There was no difference in the proportion of strokes correctly detected by the ROSIER or FAST with both displaying excellent levels of sensitivity. The ROSIER detected marginally more nonstroke cases than the FAST, but both demonstrated poor specificity. Facial weakness, arm weakness, seizure activity, age, and sex predicted consultants’ diagnosis of stroke.

Conclusions—
The ROSIER was not better than the FAST for prehospital recognition of stroke. A revised version of the FAST incorporating assessment of seizure activity may improve stroke identification and decision making by ambulance clinicians.
Dynamical Causes of the 2010/11 Texas–Northern Mexico Drought*
Authors: Seager Richard , Goddard Lisa , Nakamura Jennifer , Henderson Naomi , Lee Dong Eun 
Published: September 2013

AbstractThe causes of the Texas–northern Mexico drought during 2010–11 are shown, using observations, reanalyses, and model simulations, to arise from a combination of ocean forcing and internal atmospheric variability. The drought began in fall 2010 and winter 2010/11 as a La Niña event developed in the tropical Pacific Ocean. Climate models forced by observed sea surface temperatures (SSTs) produced dry conditions in fall 2010 through spring 2011 associated with transient eddy moisture flux divergence related to a northward shift of the Pacific–North American storm track, typical of La Niña events. In contrast the observed drought was not associated with such a clear shift of the transient eddy fields and instead was significantly influenced by internal atmospheric variability including the negative North Atlantic Oscillation of winter 2010/11, which created mean flow moisture divergence and drying over the southern Plains and southeast United States. The models suggest that drought continuation into summer 2011 was not strongly SST forced. Mean flow circulation and moisture divergence anomalies were responsible for the summer 2011 drought, arising from either internal atmospheric variability or a response to dry summer soils not captured by the models. The summer of 2011 was one of the two driest and hottest summers over recent decades but it does not represent a clear outlier to the strong inverse relation between summer precipitation and temperature in the region. Seasonal forecasts at 3.5-month lead time did predict onset of the drought in fall and winter 2010/11 but not intensification into summer 2011, demonstrating the current, and likely inherent, inability to predict important aspects of North American droughts.
Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile
Authors: Paiva Bruno , Paino Teresa , Sayagues Jose-Maria , Garayoa Mercedes , San-Segundo Laura , Martín Montserrat , Mota Ines , Sanchez María-Luz , Bárcena Paloma , Aires-Mejia Irene , Corchete Luis , Jimenez Cristina , Garcia-Sanz Ramon , Gutierrez Norma C. , Ocio Enrique M. , Mateos Maria-Victoria , Vidriales Maria-Belen , Orfao Alberto , San Miguel Jesús F. 
Published: September 2013

Key Points
Detailed characterization of myeloma circulating tumor cells shows that these represent a unique subpopulation of BM clonal PCs. Myeloma CTCs are clonogenic, quiescent, and may represent an ancestral clone potentially driven by circadian rhythms.
Ranavirus infections associated with skin lesions in lizards
Authors: Stöhr Anke C , Blahak Silvia , Heckers Kim O , Wiechert Jutta , Behncke Helge , Mathes Karina , Günther Pascale , Zwart Peer , Ball Inna , Rüschoff Birgit , Marschang Rachel E 
Published: September 2013

Abstract
Ranaviral disease in amphibians has been studied intensely during the last decade, as associated mass-mortality events are considered to be a global threat to wild animal populations. Several studies have also included other susceptible ectothermic vertebrates (fish and reptiles), but only very few cases of ranavirus infections in lizards have been previously detected. In this study, we focused on clinically suspicious lizards and tested these animals for the presence of ranaviruses. Virological screening of samples from lizards with increased mortality and skin lesions over a course of four years led to the detection of ranaviral infections in seven different groups. Affected species were: brown anoles (Anolis sagrei), Asian glass lizards (Dopasia gracilis), green anoles (Anolis carolinensis), green iguanas (Iguana iguana), and a central bearded dragon (Pogona vitticeps). Purulent to ulcerative-necrotizing dermatitis and hyperkeratosis were diagnosed in pathological examinations. All animals tested positive for the presence of ranavirus by PCR and a part of the major capsid protein (MCP) gene of each virus was sequenced. Three different ranaviruses were isolated in cell culture. The analyzed portions of the MCP gene from each of the five different viruses detected were distinct from one another and were 98.4-100% identical to the corresponding portion of the frog virus 3 (FV3) genome. This is the first description of ranavirus infections in these five lizard species. The similarity in the pathological lesions observed in these different cases indicates that ranaviral infection may be an important differential diagnosis for skin lesions in lizards.
Cyprinid herpesvirus 3: an interesting virus for applied and fundamental research
Authors: Rakus Krzysztof , Ouyang Ping , Boutier Maxime , Ronsmans Maygane , Reschner Anca , Vancsok Catherine , Jazowiecka-Rakus Joanna , Vanderplasschen Alain 
Published: September 2013

Abstract
Cyprinid herpesvirus 3 (CyHV-3), a member of the family Alloherpesviridae is the causative agent of a lethal, highly contagious and notifiable disease in common and koi carp. The economic importance of common and koi carp industries together with the rapid spread of CyHV-3 worldwide, explain why this virus became soon after its isolation in the 1990s a subject of applied research. In addition to its economic importance, an increasing number of fundamental studies demonstrated that CyHV-3 is an original and interesting subject for fundamental research. In this review, we summarized recent advances in CyHV-3 research with a special interest for studies related to host-virus interactions.
The Aeromonas salmonicida subsp. salmonicida exoproteome: determination of the complete repertoire of Type-Three Secretion System effectors and identification of other virulence factors
Authors: Vanden Bergh Philippe , Heller Manfred , Braga-Lagache Sophie , Frey Joachim 
Published: September 2013

Abstract

Background

Aeromonas salmonicida subsp. salmonicida, the etiologic agent of furunculosis, is a major pathogen of fisheries worldwide. Several virulence factors have been described, but the type-three secretion system (T3SS) is recognized as having a major effect on virulence by injecting effectors directly into fish cells. In this study we used high-throughput proteomics to display the differences between in vitro secretome of A. salmonicida wild-type (wt, hypervirulent, JF2267) and T3SS-deficient (isogenic ΔascV, extremely low-virulent, JF2747) strains in exponential and stationary phases of growth.

Results
Results confirmed the secretion of effectors AopH, AexT, AopP and AopO via T3SS, and for the first time demonstrated the impact of T3SS in secretion of Ati2, AopN and ExsE that are known as effectors in other pathogens. Translocators, needle subunits, Ati1, and AscX were also secreted in supernatants (SNs) dependent on T3SS. AopH, Ati2, AexT, AopB and AopD were in the top seven most abundant excreted proteins. EF-G, EF-Tu, DnaK, HtpG, PNPase, PepN and MdeA were moderately secreted in wt SNs and predicted to be putative T3 effectors by bioinformatics. Pta and ASA_P5G088 were increased in wt SNs and T3-associated in other bacteria. Ten conserved cytoplasmic proteins were more abundant in wt SNs than in the ΔascV mutant, but without any clear association to a secretion system. T1-secreted proteins were predominantly found in wt SNs: OmpAI, OmpK40, DegQ, insulinase ASA_0716, hypothetical ASA_0852 and ASA_3619. Presence of T3SS components in pellets was clearly decreased by ascV deletion, while no impact was observed on T1- and T2SS. Our results demonstrated that the ΔascV mutant strain excreted well-described (VapA, AerA, AerB, GCAT, Pla1, PlaC, TagA, Ahe2, GbpA and enolase) and yet uncharacterized potential toxins, adhesins and enzymes as much as or even more than the wt strain. Other putative important virulence factors were not detected.

Conclusions
We demonstrated the whole in vitro secretome and T3SS repertoire of hypervirulent A. salmonicida. Several toxins, adhesins and enzymes that are not part of the T3SS secretome were secreted to a higher extent in the extremely low-virulent ΔascV mutant. All together, our results show the high importance of an intact T3SS to initiate the furunculosis and offer new information about the pathogenesis.
Structured myeloid cells and anti-angiogenic therapy in alveolar soft part sarcoma
Authors: Castelli Chiara , Tazzari Marcella , Negri Tiziana , Vergani Barbara , Rivoltini Licia , Stacchiotti Silvia , Pilotti Silvana 
Published: September 2013

Abstract
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma and the clinical management of patients with unresectable, metastatic disease is still challenging. ASPS expresses an array of potentially therapeutically targetable, angiogenesis-related molecules and, importantly, it has a distinctive angiogenic phenotype marked by a peculiar tumor-associated vasculature. Several studies, conducted in transgenic mouse models and in a large variety of human tumors of different histotype, clearly proved the substantial contribution of tumor-infiltrating myeloid cells, such as myeloid derived suppressor cells, monocytes and macrophages, in the formation and maintenance of abnormal blood vessels in tumors. By immunohistochemistry we thus explored the presence and the distribution of cells expressing myeloid markers in the inflammatory infiltrate of surgical treated metastatic ASPS. Indeed, we found that myeloid cells expressing CD14 and CD163 markers constitute the prominent cells in the inflammatory infiltrate of ASPS. These macrophage-like cells form a network surrounding the endothelial cells, or, interspersed in the tumor nest, they keep deep contact with tumor cells. In this commentary, we discussed our findings in relation to the recently published paper by Kummar and colleagues reporting the clinical and molecular results of a phase II clinical trial in patients with unresectable, metastatic ASPS treated with the anti-angiogenic drug cediranib, targeting the VEGFR-1,-2,-3 tyrosine kinases.