bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment of (pro)renin receptor promoter with activating histone codes in the kidneys of spontaneously hypertensive rats
Authors: Lee Hae-Ahm , Lee Dong-Youb , Lee Hyo-Jung , Han Hyung Soo , Kim InKyeom 
Published: July 2011

Background: The (pro)renin receptor [(P)RR] non-proteolytically, through conformational change, activates prorenin which can convert angiotensinogen to angiotensin I in addition to the classic conversion of angiotensinogen to angiotensin I by circulating renin. Since renal (P)RR is upregulated in hypertension and implicated in the pathogenesis of malignant hypertension, we hypothesized that (pro)renin receptor promoter is enriched with activating histone codes in the kidney of spontaneously hypertensive rats (SHR). Methods: The mRNA and protein expression levels were measured by real-time polymerase chain reaction (PCR) and western blot, respectively. The DNA methylation status of (P)RR promoter region was analyzed by bisulfite sequencing. The histone modifications were determined by chromatin immunoprecipitation followed by real-time PCR. Results: The (P)RR mRNA expression in the kidney was about six times greater in SHR than in Wistar–Kyoto (WKY) rats. The (P)RR promoter was little methylated in the kidneys of both WKY and SHR. Acetylated histone H3 (H3Ac) and di-methylated histone H3 at lysine 4 (H3K4me2), activating histone codes, were about 25 and three times higher in SHR than in WKY, respectively. On the other hand, di-methylated histone H3 at lysine 9 (H3K9me2), a suppressive histone code, was 50 times lower in SHR than in WKY. Conclusion: These results suggest that the (P)RR promoter is enriched with activating histone codes in the kidneys of SHR.
Visual scanning as a reference framework for interactive representation design
Authors: Conversy Stéphane , Chatty Stéphane , Hurter Christophe 
Published: July 2011

When designing a representation, the designer implicitly formulates a sequence of visual tasks required to understand and use the representation effectively. This paper aims at making the sequence of visual tasks explicit in order to help designers elicit their design choices. In particular, we present a set of concepts to systematically analyse what a user must theoretically do to decipher representations. The analysis consists of a decomposition of the activity of scanning into elementary visualization operations. We show how the analysis applies to various existing representations, and how expected benefits can be expressed in terms of elementary operations. The set of elementary operations form the basis of a shared language for representation designers. The decomposition highlights the challenges encountered by a user when deciphering a representation and helps designers to exhibit possible flaws in their design, justify their choices, and compare designs. We also show that interaction with a representation can be considered as facilitation to perform the elementary operations. Categories and subject descriptors H.5.2 User Interfaces – evaluation/methodology, screen design. General terms design, human factors
CCL18 differentiates dendritic cells in tolerogenic cells able to prime regulatory T cells in healthy subjects
Authors: Azzaoui Imane , Yahia Saliha Ait , Chang Ying , Vorng Han , Morales Olivier , Fan Ying , Delhem Nadira , Ple Coline , Tonnel André-Bernard , Wallaert Benoit , Tsicopoulos Anne 
Published: July 2011

AbstractThe aim of this study was to evaluate the nonchemotactic function of CCL18 on human dendritic cells (DCs). In different protocols of DC differentiation, CCL18 was highly produced, suggesting that it may constitute a mandatory mediator of the differentiation process. Differentiation of monocytes from healthy subjects in the presence of granulocyte-macrophage colony-stimulating factor and CCL18 led to the development of DCs with a semimature phenotype, with intermediate levels of costimulatory and MHC class II molecules, increased CCR7 expression, which induced, in coculture with allogenic naive T cells, an increase in IL-10 production. The generated T cells were able to suppress the proliferation of effector CD4+CD25− cells, through a cytokine-dependent mechanism, and exhibited characteristics of type 1 T regulatory cells. The generation of tolerogenic DCs by CCL18 was dependent on the production of indoleamine 2,3-dioxigenase through an interleukin-10-mediated mechanism. Surprisingly, when DCs originated from allergic patients, the tolerogenic effect of CCL18 was lost in relation with a decreased binding of CCL18 to its putative receptor. This study is the first to define a chemokine able to generate tolerogenic DCs. However, this function was absent in allergic donors and may participate to the decreased tolerance observed in allergic diseases.
Biphasic roles for soluble guanylyl cyclase (sGC) in platelet activation
Authors: Zhang Guoying , Xiang Binggang , Dong Anping , Skoda Radek C. , Daugherty Alan , Smyth Susan S. , Du Xiaoping , Li Zhenyu 
Published: July 2011

AbstractNitric oxide (NO) stimulates cGMP synthesis by activating its intracellular receptor, soluble guanylyl cyclase (sGC). It is a currently prevailing concept that No and cGMP inhibits platelet function. However, the data supporting the inhibitory role of NO/sGC/cGMP in platelets have been obtained either in vitro or using whole body gene deletion that affects vessel wall function. Here we have generated mice with sGC gene deleted only in megakaryocytes and platelets. Using the megakaryocyte- and platelet-specific sGC-deficient mice, we identify a stimulatory role of sGC in platelet activation and in thrombosis in vivo. Deletion of sGC in platelets abolished cGMP production induced by either NO donors or platelet agonists, caused a marked defect in aggregation and attenuated secretion in response to low doses of collagen or thrombin. Importantly, megakaryocyte- and platelet-specific sGC deficient mice showed prolonged tail-bleeding times and impaired FeCl3-induced carotid artery thrombosis in vivo. Interestingly, the inhibitory effect of the NO donor SNP on platelet activation was sGC-dependent only at micromolar concentrations, but sGC-independent at millimolar concentrations. Together, our data demonstrate important roles of sGC in stimulating platelet activation and in vivo thrombosis and hemostasis, and sGC-dependent and -independent inhibition of platelets by NO donors.
Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet
Authors: Xie Ning , Cui Yi , Yin Ya-Ni , Zhao Xin , Yang Jun-Wen , Wang Zheng-Gen , Fu Nian , Tang Yong , Wang Xue-Hong , Liu Xiao-Wei , Wang Chun-Lian , Lu Fang-Gen 
Published: July 2011

AbstractBackgroundThe hypocholesterolemic effects of lactic acid bacteria (LAB) have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects ofLactobacillus plantarum9-41-A andLactobacillus fermentumM1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet.MethodsForty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented withLactobacillus plantarum9-41-A orLactobacillus fermentumM1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically.ResultsCompared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p < 0.05), with no significant change in high-density lipoprotein cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid deposition were significantly decreased in the LAB-treated groups (p < 0.05). Accordingly, both fecal cholesterol and bile acids levels were significantly increased after LAB administration (p < 0.05). IntestinalLactobacillusandBifidobacteriumcolonies were increased whileEscherichia colicolonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration ofLactobacillus plantarum9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p < 0.05).ConclusionsThis study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown,L. plantarum9-41-A may play a role in fat metabolism.
Heteroarylketones inhibit astroglial interleukin-6 expression via a STAT3/NF-κB signaling pathway
Authors: Schulz Ingo , Engel Claudia , Niestroj André J , Zeitschel Ulrike , Menge Katja , Kehlen Astrid , Meyer Antje , Roßner Steffen , Demuth Hans-Ulrich 
Published: July 2011

AbstractBackgroundElevated brain levels of the pleiotropic cytokine interleukin-6, which is mainly secreted from activated local astrocytes, contribute to pathological events including neuroinflammation and neurodegeneration. Thus, inhibition of pathological IL-6 expression provides a rationale strategy for targeting the onset or further progression of neurological disorders including Alzheimer's disease, multiple sclerosis, Parkinson's disease and traumatic brain injury. The purpose of this study was to identify and to characterize new potent inhibitors of astrocytic IL-6 expression for further therapeutic development of novel anti-inflammatory and neuroprotective drugs.MethodsOncostatin M (OSM)-treated human glioma U343 cells were used as model for induction of astrocytic IL-6 expression. This model was characterized by immunoblotting, siRNA technique, ELISA and qRT-PCR and used to screen low molecular weight compound libraries for IL-6-lowering effects. To validate bioactive compounds identified from library screens, bacterial lipopolysaccharide was used to induce IL-6 expression in cultivated primary astrocytes and in micein vivo. To dissect underlying molecular mechanisms, protein extracts from OSM-treated U343 cells were analyzed by phospho-specific immunoblotting and immunocytochemistry as well as by co-immunoprecipitation.ResultsOSM-treatment (100 ng/ml; 24 h) led to 30-fold increase of IL-6 secretion from U343 cells. The temporal profile of IL-6 mRNA induction displayed a biphasic induction pattern with peak synthesis at 1 h (6.5-fold) and 16 h (5.5-fold) post stimulation. IL-6 protein release did not show that biphasic pattern and was detected as early as 3 h post stimulation reaching a maximum at 24 h. The screen of compound libraries identified a set of heteroarylketones (HAKs) as potent inhibitors of IL-6 secretion. HAK compounds affected the second peak in IL-6 mRNA synthesis, whereas the first peak was insensitive to HAK treatment. HAK compounds also suppressed lipopolysaccharide-induced IL-6 expression in primary murine astrocytes as well as in brain and plasma samples from lipopolysaccharide-treated mice. Finally, HAK compounds were demonstrated to specifically suppress the OSM-induced phosphorylation of STAT3 at serine 727 and the physical interaction of pSTAT3S727with p65.ConclusionHeteroarylketone compounds are potent inhibitors of IL-6 expressionin vitroandin vivoand may represent a new class of potent anti-inflammatory and neuroprotective drugs.
The accuracy of echocardiography versus surgical and pathological classification of patients with ruptured mitral chordae tendineae: a large study in a Chinese cardiovascular center
Authors: Wu Weichun , Luo Xiaoliang , Wang Linlin , Sun Xin , Jiang Yong , Huo Shunwei , Tu Dalou , Bai Zhigang , Wang Hao 
Published: July 2011

Abstract

Background
The accuracy of echocardiography versus surgical and pathological classification of patients with ruptured mitral chordae tendineae (RMCT) has not yet been investigated with a large study.

Methods
Clinical, hemodynamic, surgical, and pathological findings were reviewed for 242 patients with a preoperative diagnosis of RMCT that required mitral valvular surgery. Subjects were consecutive in-patients at Fuwai Hospital in 2002-2008. Patients were evaluated by thoracic echocardiography (TTE) and transesophageal echocardiography (TEE). RMCT cases were classified by location as anterior or posterior, and classified by degree as partial or complete RMCT, according to surgical findings. RMCT cases were also classified by pathology into four groups: myxomatous degeneration, chronic rheumatic valvulitis (CRV), infective endocarditis and others.

Results
Echocardiography showed that most patients had a flail mitral valve, moderate to severe mitral regurgitation, a dilated heart chamber, mild to moderate pulmonary artery hypertension and good heart function. The diagnostic accuracy for RMCT was 96.7% for TTE and 100% for TEE compared with surgical findings. Preliminary experiments demonstrated that the sensitivity and specificity of diagnosing anterior, posterior and partial RMCT were high, but the sensitivity of diagnosing complete RMCT was low. Surgical procedures for RMCT depended on the location of ruptured chordae tendineae, with no relationship between surgical procedure and complete or partial RMCT. The echocardiographic characteristics of RMCT included valvular thickening, extended subvalvular chordae, echo enhancement, abnormal echo or vegetation, combined with aortic valve damage in the four groups classified by pathology. The incidence of extended subvalvular chordae in the myxomatous group was higher than that in the other groups, and valve thickening in combination with AV damage in the CRV group was higher than that in the other groups. Infective endocarditis patients were younger than those in the other groups. Furthermore, compared other groups, the CRV group had a larger left atrium, higher aortic velocity, and a higher pulmonary arterial systolic pressure.

Conclusions
Echocardiography is a reliable method for diagnosing RMCT and is useful for classification. Echocardiography can be used to guide surgical procedures and for preliminary determination of RMCT pathological types.
Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats
Authors: Kitamura Yoshihisa , Watanabe Shotaro , Taguchi Masanobu , Takagi Kentaro , Kawata Takuya , Takahashi-Niki Kazuko , Yasui Hiroyuki , Maita Hiroshi , Iguchi-Ariga Sanae MM , Ariga Hiroyoshi 
Published: July 2011

Abstract

Background
Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD.

Results
In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B.

Conclusions
The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.
Solid variant of aneurysmal bone cyst of the thoracic spine: a case report
Authors: Al-Shamy George , Relyea Katherine , Adesina Adekunle , Whitehead William E , Curry Daniel J , Luerssen Thomas G , Jea Andrew 
Published: July 2011

Abstract

Introduction
The solid variant of aneurysmal bone cyst is rare, and only 13 cases involving the spine have been reported to date, including seven in the thoracic vertebrae. The diagnosis is difficult to secure radiographically before biopsy or surgery.

Case report
An 18-year-old Hispanic man presented to our facility with a one-year history of left chest pain without any significant neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi-cystic mass centered at the T6 vertebral body with involvement of the left proximal sixth rib and extension into the pleural cavity; the spinal cord was severely compressed with evidence of abnormal T2 signal changes. Our patient was taken to the operating room for a total spondylectomy of T6 with resection of the left sixth rib from a single-stage posterior-only approach. The vertebral column was reconstructed in a 360° manner with an expandable titanium cage and pedicle screw fixation. Histologically, the resected specimen showed predominant solid fibroblastic proliferation, with minor foci of reactive osteoid formation, an area of osteoclastic-like giant cells, and cyst-like areas filled with erythrocytes and focal hemorrhage, consistent with a predominantly solid variant of aneurysmal bone cyst. At 16 months after surgery, our patient remains neurologically intact with resolution of his chest and back pain.

Conclusions
Because of its rarity, location, and radical treatment approach, we considered this case worthy of reporting. The solid variant of aneurysmal bone cyst is difficult to diagnose radiologically before biopsy or surgery, and we hope to remind other physicians that it should be included in the differential diagnosis of any lytic expansile destructive lesion of the spine.
Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report
Authors: Hidaka Masaaki , Takatsuki Mitsuhisa , Soyama Akihiko , Miyaaki Hisamitsu , Ichikawa Tatsuki , Nakao Kazuhiko , Kanematsu Takashi , Eguchi Susumu 
Published: July 2011

Abstract

Introduction
Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.

Case presentation
A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection.

Conclusions
A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.
Colonization of Phlebotomus papatasi changes the effect of pre-immunization with saliva from lack of protection towards protection against experimental challenge with Leishmania major and saliva
Authors: Ben Hadj Ahmed Sami , Kaabi Belhassen , Chelbi Ifhem , Cherni Saifeddine , Derbali Mohamed , Laouini Dhafer , Zhioua Elyes 
Published: July 2011

AbstractBackgroundSand fly saliva has been postulated as a potential vaccine or as a vaccine component within multi component vaccine against leishmaniasis. It is important to note that these studies were performed using long-term colonizedPhlebotomus papatasi. The effect of sand flies colonization on the outcome ofLeishmaniainfection is reported.ResultsWhile pre-immunization of mice with salivary gland homogenate (SGH) of long-term colonized (F5 and beyond) femalePhlebotomus papatasiinduced protection againstLeishmania majorco-inoculated with the same type of SGH, pre-immunization of mice with SGH of recently colonized (F2 and F3) femaleP. papatasidid not confer protection againstL. majorco-inoculated with the same type of SGH. Our data showed for the first time that a shift from lack of protection to protection occurs at the fourth generation (F4) during the colonization process ofP. papatasi.ConclusionFor the development of a sand fly saliva-based vaccine, inferences based on long-term colonized populations of sand flies should be treated with caution as colonization ofP. papatasiappears to modulate the outcome ofL. majorinfection from lack of protection to protection.