bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats
Authors: Mattioli L , Funari C , Perfumi M 
Published: May 2008

Abstract Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R. rosea L. extract in rats exposed to acute stress. There is increasing evidence that prolonged exposure to stressful life events and depression are both related to significant behavioural, endocrinological and neurobiological changes in human and animal subjects. The aim of this study was to determine whether chronic treatment with a hydroalcoholic R. rosea extract (RHO) standardized in 3% rosavin and 1% salidroside can prevent alterations induced in female rats following 6 weeks of a chronic mild stress (CMS) procedure. This was analysed through the behavioural and physiological parameters of consumption of 1% sucrose solution, locomotor and exploratory activities, body weight gain and oestrous cycle length. After the first 3 weeks of stress, RHO was administered daily by gavage at doses of 10, 15 and 20 mg/kg for the remaining 3 weeks. In addition, the antidepressant drug fluoxetine (10 mg/kg os), which has been shown to reverse CMS-induced disruptions, was used as the reference treatment. Rats subjected to the CMS procedure demonstrated decreased sucrose intake, reduced moving behaviour, minimized weight gain and dysregulation of their oestrous cycle. Treatment with RHO completely reverted all of these changes. The effects of RHO were comparable to those of fluoxetine. Interestingly, neither RHO nor fluoxetine influence the behavioural and physiological parameters tested in non-stressed animals. These findings strongly showed that chronic administration of RHO results in potent inhibition of the behavioural and physiological changes induced by chronic exposure to mild stressors.
Angiostatic activity of the antitumor cytokine interleukin-21
Authors: Castermans Karolien , Tabruyn Sebastien P. , Zeng Rong , van Beijnum Judy R. , Eppolito Cheryl , Leonard Warren J. , Shrikant Protul A. , Griffioen Arjan W. 
Published: May 2008

AbstractInterleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.
Dexamethasone-induced apoptotic mechanisms in myeloma cells investigated by analysis of mutant glucocorticoid receptors
Authors: Sharma Sanjai , Lichtenstein Alan 
Published: May 2008

AbstractThe mechanism by which the glucocorticoid (GC) dexamethasone induces apoptosis in multiple myeloma (MM) cells is unknown, although previous work suggests that either transactivation through the glucocorticoid response element (GRE), transrepression of NF-κB, phosphorylation of RAFTK (Pyk2), or induction of Bim is important. We studied this question by ectopically expressing mutant glucocorticoid receptors (GRs) in the dexamethasone-resistant MM1R cell line, which has lost its GR. Lentiviral-mediated reexpression of wild-type GR restored GRE transactivation, NF-κB transrepression, RAFTK phosphorylation, Bim induction, and dexamethasone-induced apoptosis. We then reexpressed 4 GR mutants, each possessing various molecular effects, into MM1R cells. A perfect correlation was present between induction of GRE transactivation and induction of apoptosis. In contrast, NF-κB transrepression and RAFTK phosphorylation were not required for apoptosis. Although not required for dexamethasone-mediated apoptosis, NF-κB inhibition achieved by gene transfer suggested that NF-κB transrepression could contribute to apoptosis in dexamethasone-treated cells. Dexamethasone treatment of MM1R cells expressing a mutant incapable of inducing apoptosis successfully resulted in RAFTK (Pyk2) phosphorylation and Bim induction indicating the latter GR-mediated events were not sufficient to induce apoptosis. MM1R cells expressing mutant GRs will be helpful in defining the molecular mechanisms of dexamethasone-induced apoptosis of myeloma cells.
Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family
Authors: Danilova Nadia , Sakamoto Kathleen M. , Lin Shuo 
Published: May 2008

AbstractMutations in several ribosomal proteins (RPs) lead to Diamond-Blackfan anemia (DBA), a syndrome characterized by defective erythropoiesis, congenital anomalies, and increased frequency of cancer. RPS19 is the most frequently mutated RP in DBA. RPS19 deficiency impairs ribosomal biogenesis, but how this leads to DBA or cancer remains unknown. We have found that rps19 deficiency in ze-brafish results in hematopoietic and developmental abnormalities resembling DBA. Our data suggest that the rps19-deficient phenotype is mediated by dysregulation of deltaNp63 and p53. During gastrulation, deltaNp63 is required for specification of nonneural ectoderm and its up-regulation suppresses neural differentiation, thus contributing to brain/craniofacial defects. In rps19-deficient embryos, deltaNp63 is induced in erythroid progenitors and may contribute to blood defects. We have shown that suppression of p53 and deltaNp63 alleviates the rps19-deficient phenotypes. Mutations in other ribosomal proteins, such as S8, S11, and S18, also lead to up-regulation of p53 pathway, suggesting it is a common response to ribosomal protein deficiency. Our finding provides new insights into pathogenesis of DBA. Ribosomal stress syndromes represent a broader spectrum of human congenital diseases caused by genotoxic stress; therefore, imbalance of p53 family members may become a new target for therapeutics.
JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders
Authors: Plo Isabelle , Nakatake Mayuka , Malivert Laurent , de Villartay Jean-Pierre , Giraudier Stéphane , Villeval Jean-Luc , Wiesmuller Lisa , Vainchenker William 
Published: May 2008

AbstractThe JAK2V617F mutation is frequently observed in classical myeloproliferative disorders, and disease progression is associated with a biallelic acquisition of the mutation occurring by mitotic recombination. In this study, we examined whether JAK2 activation could lead to increased homologous recombination (HR) and genetic instability. In a Ba/F3 cell line expressing the erythropoietin (EPO) receptor, mutant JAK2V617F and, to a lesser extent, wild-type (wt) JAK2 induced an increase in HR activity in the presence of EPO without modifying nonhomologous end-joining efficiency. Moreover, a marked augmentation in HR activity was found in CD34+-derived cells isolated from patients with polycythemia vera or primitive myelofibrosis compared with control samples. This increase was associated with a spontaneous RAD51 foci formation. As a result, sister chromatid exchange was 50% augmented in JAK2V617F Ba/F3 cells compared with JAK2wt cells. Moreover, JAK2 activation increased centrosome and ploidy abnormalities. Finally, in JAK2V617F Ba/F3 cells, we found a 100-fold and 10-fold increase in mutagenesis at the HPRT and Na/K ATPase loci, respectively. Together, this work highlights a new molecular mechanism for HR regulation mediated by JAK2 and more efficiently by JAK2V617F. Our study might provide some keys to understand how a single mutation can give rise to different pathologies.
Protein contact order prediction from primary sequences
Authors: Shi Yi , Zhou Jianjun , Arndt David , Wishart David S , Lin Guohui 
Published: May 2008

Abstract

Background
Contact order is a topological descriptor that has been shown to be correlated with several interesting protein properties such as protein folding rates and protein transition state placements. Contact order has also been used to select for viable protein folds from ab initio protein structure prediction programs. For proteins of known three-dimensional structure, their contact order can be calculated directly. However, for proteins with unknown three-dimensional structure, there is no effective prediction method currently available.

Results
In this paper, we propose several simple yet very effective methods to predict contact order from the amino acid sequence only. One set of methods is based on a weighted linear combination of predicted secondary structure content and amino acid composition. Depending on the number of components used in these equations it is possible to achieve a correlation coefficient of 0.857–0.870 between the observed and predicted contact order. A second method, based on sequence similarity to known three-dimensional structures, is able to achieve a correlation coefficient of 0.977. We have also developed a much more robust implementation for calculating contact order directly from PDB coordinates that works for > 99% PDB files. All of these contact order predictors and calculators have been implemented as a web server (see Availability and requirements section for URL).

Conclusion
Protein contact order can be effectively predicted from the primary sequence, at the absence of three-dimensional structure. Three factors, percentage of residues in alpha helices, percentage of residues in beta strands, and sequence length, appear to be strongly correlated with the absolute contact order.
Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium
Authors: Sridhar Sriram , Schembri Frank , Zeskind Julie , Shah Vishal , Gustafson Adam M , Steiling Katrina , Liu Gang , Dumas Yves-Martine , Zhang Xiaohui , Brody Jerome S , Lenburg Marc E , Spira Avrum 
Published: May 2008

Abstract

Background
Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers.

Results
Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure.

Conclusion
Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.
Diagnostic utility of LunXmRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer
Authors: Cheng Min , Chen Yongyan , Yu Xiaoqing , Tian Zhigang , Wei Haiming 
Published: May 2008

Abstract

Background
Progress in lung cancer is hampered by the lack of clinically useful diagnostic markers. The goal of this study was to provide a detailed evaluation of lung cancer tumor markers indicative of molecular abnormalities and to assess their diagnostic utility in non-small cell lung cancer (NSCLC) patients.

Methods
Quantitative real-time RT-PCR was used to determine LunX, CK19, CEA, VEGF-C and hnRNP A2/B1 mRNA levels in peripheral blood and pleural fluid from NSCLC patients, compared with those from patients with other epithelial cancer (esophagus cancer and breast cancer), benign lung disease (pneumonia and tuberculo pleurisy) and from healthy volunteers.

Results
In peripheral blood LunX mRNA was detectable in 75.0% (33/44) of patients with NSCLC, but not in patients with other epithelial cancer (0/28), benign lung disease (0/10) or in healthy volunteers (0/15). In contrast, all other genetic markers were detected in patients with either NSCLC, other epithelia cancer or benign lung disease, and in healthy volunteers. The expression level and positive rate of LunX mRNA in peripheral blood correlated with the pathologic stage of NSCLC (P < 0.001 and P = 0.010 respectively). Furthermore, LunX mRNA was detected in 92.9% (13/14) of malignant pleural fluid samples and was the only marker whose expression level was significantly different between malignant and benign pleural fluid (P < 0.001). Additionally, expression of LunX mRNA in the peripheral blood of NSCLC patients decreased shortly after clinical treatment (P = 0.005).

Conclusion
Of several commonly used genetic markers, LunX mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid of NSCLC patients.
CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations
Authors: Sandhya Sankaran , Pankaj Barah , Govind Madabosse Kande , Offmann Bernard , Srinivasan Narayanaswamy , Sowdhamini Ramanathan 
Published: May 2008

Abstract

Background
Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains.

Results
CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends.

Conclusion
The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.
In vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity
Authors: Verma Saguna , Molina Yanira , Lo Yeung Y , Cropp Bruce , Nakano Cheynie , Yanagihara Richard , Nerurkar Vivek R 
Published: May 2008

Abstract

Background
Selenium (Se) deficiency plays an important role in viral pathogenesis. To understand the effects of Se deficiency on West Nile virus (WNV) infection, we analyzed cytopathogenicity, apoptosis and viral replication kinetics, using a newly developed Se-deficient cell culture system.

Results
Both Vero and SK-N-SH cells grown in Se-deficient media exhibited a gradual loss of glutathione peroxidase (GPx1) activity without any significant effect on cell growth and viability. In SK-N-SH cells, Se deficiency had no effect on the expression of key antioxidant enzymes, including manganese- and copper-zinc superoxide dismutase (MnSOD and CuZnSOD), catalase and inducible nitric oxide synthase, whereas Vero cells demonstrated a significant increase in the expression of MnSOD and an overall increase in oxidative stress (OS) at day 7 post-induction of Se deficiency. At 2 days after infection with WNV, CPE and cell death were significantly higher in WNV-infected Se-deficient Vero cells, compared to WNV-infected control cells. Furthermore, WNV-induced apoptosis was significantly heightened in Se-deficient cells and was contributed by loss of mitochondrial membrane potential and increased caspase activity. However, no significant difference was found in WNV copy numbers between control, Se-adequate and Se-deficient cell cultures.

Conclusion
Overall results demonstrate that the in vitro Se-deficient model can be used to study responses of WNV to this essential nutrient. Although Se deficiency has no in vitro effect on WNV replication kinetics, adequate Se is presumably critical to protect WNV-infected cells against virus-induced cell death.
Prevalence of four different subgenotypes of genotype 4 hepatitis E virus among swine in the Shanghai area of China
Authors: Yan Yijia , Zhang Wen , Shen Quan , Cui Li , Hua Xiuguo 
Published: May 2008

Abstract

Background
Hepatitis E virus (HEV) is a zoonotic pathogen of which swine was reported as major reservoirs. HEV has been divided into 4 different genotypes according to phylogenetic analysis. Recent reports showed that genotype 4 HEV is freely transmitted between humans and swine in eastern China, including Shanghai area. This paper investigated the recent infection status of HEV among swine population of Shanghai area in China.

Methods
480 swine faecal specimens were collected from 23 farms which distribute all over Shanghai from September to November, 2007 and tested for the presence of HEV RNA by the polymerase chain reaction (PCR).

Results
Our results showed that 26.1% (6/23) of the swine farms were positive for HEV RNA and the positive rate of the six farms were ranged from 9.1% to 33.3%. The HEV RNA positive rate for total samples were 5% (24/480). The resulted positive band specific for HEV was sequenced and sequence analysis indicated that all of these isolates belonged to genotype 4 HEV. Phylogenetic analysis showed that the 24 isolates clustered into 4 distinct subgroups, sharing 83.3–89.7% inter-subgroup and 97–99% intra-subgroup identities. More over, isolates in three of the four subgroups closely clustered with previous identified strains, sharing up high to 97% identity with them.

Conclusion
These results suggested that there were 4 different subgenotypes of HEV prevalent in Shanghai, and some of them may not be indigenous to Shanghai but introduced from other geographic regions.
Surgical treatment and outcome of pulmonary hamartoma: a retrospective study of 20-year experience
Authors: Guo Wei , Zhao Yun-Ping , Jiang Yao-Guang , Wang Ru-Wen , Ma Zheng 
Published: May 2008

Abstract

Background
Controversy still exists in the indication and timing of surgical treatment of pulmonary hamartoma (PH). The objective of this study is to summarize the experience and the outcome of the surgical treatment for pulmonary hamartomas, and to assess the effectiveness and necessity of surgical therapy administered in patients with pulmonary hamatoma as well as clinical and pathological features and long-term follow-up results.

Methods
This retrospective report has reviewed a 20-years clinical history of surgical treatment for 39 patients with PH from 1985 to 2006. These thirty-nine patients underwent 40 operations as follows: wedge resection (23), enucleation (10), segmentectomy (3), lobectomy (3), and pneumonectomy (1).

Results
The PH occurred most frequently (78.1%) in the patients aged 40 to 60 years and the sex ratio (male/female) was 2.25/1 in our series. No postoperative death was encountered. One patient with pleural effusion was cured after thoracentesis. All of these 39 patients were proved with pathologic diagnosis of PH and the popcorn calcification was found in 6 cases before operation. In 38 cases having the mean follow-up of 7.3 years, a patient was operated thrice for regional recurrence.

Conclusion
Fast frozen section in operation is critical for acquire accurate pathological diagnosis. Due to potential trend of recurrence or malignance, patients with hamartoma should be submitted to a complete evaluation and a regular follow-up.
Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils
Authors: Alba Gonzalo , El Bekay Rajaa , Chacón Pedro , Reyes M Edith , Ramos Eladio , Oliván Josefina , Jiménez Juan , López José M , Martín-Nieto José , Pintado Elízabeth , Sobrino Francisco 
Published: May 2008

AbstractAngiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Δ12,14-PGJ2 (15dPGJ2). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ2-dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ2 on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ2-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.