bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Chaperone gp96 Is a Novel Therapeutic Target of Multiple Myeloma
Authors: Hua Yunpeng , White-Gilbertson Shai , Kellner Joshua , Rachidi Saleh , Usmani Saad Z. , Chiosis Gabriela , DePinho Ronald , Li Zihai , Liu Bei 
Published: September 2013

AbstractPurpose: gp96 (grp94) is a key downstream chaperone in the endoplasmic reticulum (ER) to mediate unfolded protein response (UPR) and the pathogenesis of multiple myeloma is closely linked to dysregulated UPR. In this study, we aimed to determine the roles of gp96 in the initiation and progression of multiple myeloma in vivo and in vitro.Experimental Design: We generated a mouse model with overexpression of XBP1s and conditional deletion of gp96 in B-cell compartment simultaneously to identify the roles of gp96 in the development of multiple myeloma in vivo. Using a short hairpin RNA (shRNA) system, we silenced gp96 in multiple human multiple myeloma cells and examined the effect of gp96 knockdown on multiple myeloma cells by cell proliferation, cell-cycle analysis, apoptosis assay, immunohistochemistry, and human myeloma xenograft model. The anticancer activity of gp96 selective inhibitor, WS13, was evaluated by apoptosis assay and MTT assay.Results: Genetic deletion of gp96 in XBP1s-Tg mice attenuates multiple myeloma. Silencing of gp96 causes severe compromise in human multiple myeloma cell growth through inhibiting Wnt-LRP-survivin pathway. We also confirmed that knockdown of gp96 decreased human multiple myeloma growth in a murine xenograft model. The targeted gp96 inhibitor induced apoptosis and blocked multiple myeloma cell growth, but did not induce apoptosis in pre-B leukemic cells. We have demonstrated that myeloma growth is dependent on gp96 both genetically and pharmacologically.Conclusions: gp96 is essential for multiple myeloma cell proliferation and survival, suggesting that gp96 is a novel therapeutic target for multiple myeloma. Clin Cancer Res; 19(22); 6242–51. ©2013 AACR.
The Status of Mothers in the Early Chinese Mourning System
Authors: Zhou Yiqun 
Published: September 2013

This essay examines the prescriptions on mourning for mothers in the Yili and the Liji, aiming to bring out the complex and evolving nature of the status of mothers in the centuries that saw the initial codification of the Chinese mourning system. The discrepancies between texts and within the same text, together with the ambiguity and lacunae in prescriptions, show that women’s identities in the patrilineal family were continuously contested and reshaped in the preimperial and early imperial periods. Major themes explored include: the fragmentation and fluidity of maternal roles, the tension between patrilineal principles and natural feelings, the ambivalent roles of divorced mothers and remarried mothers, the systematic suppression of mothers of concubine status, and the intricate linkage between the wife’s status and the mother’s status. The changes and ambiguities emphasized in the paper have important implications for our understanding of the later evolution of the mourning system. Cet article s’intéresse aux prescriptions relatives au deuil des mères dans le Yili et le Liji; l’objectif est de mettre en évidence la complexité et le caractère évolutif du statut des mères pendant les siècles qui ont vu les débuts de la codification du système de deuil en Chine. Les divergences entre les textes ou à l’intérieur d’un même texte, en même temps que les ambiguïtés et les lacunes des prescriptions, montrent que les identités féminines au sein de la famille patrilinéaire n’ont cessé d’être contestées et refaçonnées pendant la période pré-impériale et au début de l’empire. Les principaux thèmes abordés incluent la fragmentation et la fluidité des rôles maternels, la tension entre les principes patrilinéaires et les sentiments naturels, le rôle ambivalent des mères divorcées ou remariées, le refoulement systématique des mères ayant le statut de concubines, et les relations complexes entre le statut de l’épouse et celui de la mère. Les évolutions et les ambiguïtés mises en avant dans l’article ont des implications importantes pour notre compréhension de l’évolution ultérieure du système de deuil.
Compression versus inner sole for venous patients with foot static disorders: a prospective trial comparing symptoms and quality of life
Authors: Uhl Jean-François , Chahim Maxime , Allaert François-André 
Published: September 2013

Objective To prospectively compare the improvement in quality of life and symptoms achieved when using two treatments—medical compression stockings and inner sole—in subjects with symptomatic chronic venous disease in the presence of foot static disorders. Materials and methods This prospective study included 24 patients with a symptomatic chronic venous disease associated with foot static disorders. The basic CEAP was used to classify the patients. The venous symptoms were recorded using a 10-point visual analog scale and scored using a customized questionnaire. Patient-reported quality of life data were acquired using a CIVIC questionnaire. A standardized measurement of the Djian-Annonier angle was used to quantify the foot static disorders. We compared the use of the following two treatments: medical compression stockings (18 mm of Hg) and inner sole. For this comparison, we used a crossover technique over 4 successive weeks. Results One male and 23 female patients were included in this study. We found significant improvement in quality of life scores when only medical compression stockings were used ( p < 0.005), only inner sole were used ( p < 0.01) and also when both treatments were used together ( p < 0.001), compared with no treatment. This was mainly observed for the somatic component of CIVIC. The symptoms of pain, heaviness, swollen feeling, and cramps were significantly improved by the two treatments, whether given separately ( p < 0.001) or together ( p < 0.0001). No additive effect of the treatments was observed. Conclusion This study suggests that a number of leg symptoms occurring in varicose veins patients are not likely to have a venous origin. They are frequently related to a foot static disorder, which is responsible for postural changes. This study also strongly demonstrates the need for correction of the foot static disorder if such a disorder is present in any patient with chronic venous disease. The use of the inner sole will improve the symptoms and also the quality of life with an efficiency that is almost equal to that provided by the medical compression stockings and the combined use of both treatments is recommended.
Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009 vaccine in young autoimmune rheumatic diseases patients
Authors: Aikawa NE , Trudes G , Campos LMA , Pereira RMR , Moraes JCB , Ribeiro AC , Miraglia J , Timenetsky M do Carmo S , Bonfa E , Silva CA 
Published: September 2013

Objectives The aim of this study was to evaluate the immunogenicity and safety of the influenza A H1N1/2009 vaccine in children under 9 years old with autoimmune rheumatic diseases (ARD). Methods Thirty-eight ARD patients and 11 healthy children received two doses of non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and 21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers (GMT) and factor increases (FI) in GMT were calculated. Results Mean ages were comparable between patients and controls. Pre-vaccination SP and GMT were similar in patients and controls ( p > 0.05). Three weeks after immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were similar in patients and controls, with both groups achieving an adequate response, according to the European Medicines Agency and Food and Drug Administration standards. Analysis of the possible factors influencing SC showed no difference in demographic data, leukocyte/lymphocyte counts or immunosuppressant use between seroconverted and non-seroconverted patients ( p > 0.05). The vaccine demonstrated a satisfactory safety profile in this population. Conclusions Two doses of influenza A H1N1/2009 vaccination induced an effective antibody response and caused adverse events in rare instances, suggesting this vaccine is appropriate and can be recommended for this age group.
Medium-Term Results After Treatment of Recalcitrant Lateral Epicondylitis
Authors: Meknas Khaled , Al Hassoni Thabit N. , Odden-Miland Åshild , Castillejo Miguel , Kartus Jüri 
Published: September 2013

Background: Recalcitrant lateral epicondylitis (elbow extensor–origin tendinosis) is a common cause of elbow pain with many treatment options. In the present study, the medium-term results after open release and radiofrequency microtenotomy are reported. Hypothesis: Microtenotomy would provide long-term pain relief that was as good as the open release method. Study Design: Prospective, randomized trial. Methods: Twenty-four patients randomized to either open release or microtenotomy were assessed after 5 to 7 years. Clinical examination and dynamic infrared thermography (DIRT) of both elbows were performed preoperatively and at the medium-term follow-up. Magnetic resonance imaging (MRI) of both elbows was performed at the medium-term follow-up. Results: Significant pain reduction was found using a visual analog scale (VAS) at the medium-term follow-up in both groups compared with the preoperative assessment ( P < .005). The Mayo Elbow Performance Score (MEPS) increased significantly in both groups ( P < .01). The improvement in grip strength was not significant in either group. There was no significant difference between the groups in terms of VAS, strength, and the MEPS. On the DIRT examinations, there were significantly fewer hot spots at the medium-term follow-up than preoperatively ( P = .0067, both study groups together). The MRI examinations revealed grade II changes in the operated elbow in 1 patient in each group at the medium-term follow-up, while all the other MRI examinations revealed a normal tendon. Conclusion: In this prospective, randomized trial with a medium-term follow-up, the results were similar after surgical release and microtenotomy in patients with recalcitrant lateral epicondylitis. The hypothesis was thus verified.
Dengue virus type 1 clade replacement in recurring homotypic outbreaks
Authors: Teoh Boon-Teong , Sam Sing-Sin , Tan Kim-Kee , Johari Jefree , Shu Meng-Hooi , Danlami Mohammed Bashar , Abd-Jamil Juraina , MatRahim NorAziyah , Mahadi Nor Muhammad , AbuBakar Sazaly 
Published: September 2013

AbstractBackgroundRecurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control.ResultsWe used a set of viral envelope (E) gene to reconstruct the phylogeny of DENV-1 isolated between the periods of 1987–2011 in Malaysia. Phylogenetic analysis of DENV-1 E gene revealed that genotype I virus clade replacements were associated with the cyclical pattern of major DENV-1 outbreaks in Malaysia. A total of 9 non-conservative amino acid substitutions in the DENV-1 E gene consensus were identified; 4 in domain I, 3 in domain II and 2 in domain III. Selection pressure analyses did not reveal any positively selected codon site within the full length E gene sequences (1485 nt, 495 codons). A total of 183 (mean dN/dS= 0.0413) negatively selected sites were found within the Malaysian isolates; neither positive nor negative selection was noted for the remaining 312 codons. All the viruses were cross-neutralized by the respective patient sera suggesting no strong support for immunological advantage of any of the amino acid substitutions.ConclusionDENV-1 clade replacement is associated with recurrences of major DENV-1 outbreaks in Malaysia. Our findings are consistent with those of other studies that the DENV-1 clade replacement is a stochastic event independent of positive selection.
RIP-seq of BmAgo2-associated small RNAs reveal various types of small non-coding RNAs in the silkworm, Bombyx mori
Authors: Nie Zuoming , Zhou Fang , Li Dan , Lv Zhengbing , Chen Jian , Liu Yue , Shu Jianhong , Sheng Qing , Yu Wei , Zhang Wenping , Jiang Caiying , Yao Yuhua , Yao Juming , Jin Yongfeng , Zhang Yaozhou 
Published: September 2013

Abstract

Background
Small non-coding RNAs (ncRNAs) are important regulators of gene expression in eukaryotes. Previously, only microRNAs (miRNAs) and piRNAs have been identified in the silkworm, Bombyx mori. Furthermore, only ncRNAs (50-500nt) of intermediate size have been systematically identified in the silkworm.

Results
Here, we performed a systematic identification and analysis of small RNAs (18-50nt) associated with the Bombyx mori argonaute2 (BmAgo2) protein. Using RIP-seq, we identified various types of small ncRNAs associated with BmAGO2. These ncRNAs showed a multimodal length distribution, with three peaks at ~20nt, ~27nt and ~33nt, which included tRNA-, transposable element (TE)-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. The tRNA-derived fragments (tRFs) were found at an extremely high abundance and accounted for 69.90% of the BmAgo2-associated small RNAs. Northern blotting confirmed that many tRFs were expressed or up-regulated only in the BmNPV-infected cells, implying that the tRFs play a prominent role by binding to BmAgo2 during BmNPV infection. Additional evidence suggested that there are potential cleavage sites on the D, anti-codon and TψC loops of the tRNAs. TE-derived small RNAs and piRNAs also accounted for a significant proportion of the BmAgo2-associated small RNAs, suggesting that BmAgo2 could be involved in the maintenance of genome stability by suppressing the activities of transposons guided by these small RNAs. Finally, Northern blotting was also used to confirm the Bombyx 5.8 s rRNA-derived small RNAs, demonstrating that various novel small RNAs exist in the silkworm.

Conclusions
Using an RIP-seq method in combination with Northern blotting, we identified various types of small RNAs associated with the BmAgo2 protein, including tRNA-, TE-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. Our findings provide new clues for future functional studies of the role of small RNAs in insect development and evolution.
Expression of activator protein-1 (AP-1) family members in breast cancer
Authors: Kharman-Biz Amirhossein , Gao Hui , Ghiasvand Reza , Zhao Chunyan , Zendehdel Kazem , Dahlman-Wright Karin 
Published: September 2013

Abstract

Background
The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer.

Methods
We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses.

Results
We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01).

Conclusions
Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer.
Undifferentiated embryonal sarcoma of the liver in a middle-aged adult with systemic lupus erythematosus
Authors: Jia Changjun , Zhao Wei , Dai Chaoliu , Wang Xinlu , Bu Xianmin , Peng Songlin , Xu Feng , Xu Yongqing , Zhao Yang 
Published: September 2013

Abstract
Adult primary undifferentiated embryonal sarcoma of the liver (UESL) is a rare disease. While the etiology of UESL remains largely unknown, association with systemic inflammatory disorders has been observed. Here, we report a case of UESL in a 46-year-old woman with systemic lupus erythematosus (SLE) and without chronic hepatitis or liver cirrhosis. Systematic review of the publicly available English language medical literature identified only 27 cases of UESL in patients aged >45 years and none with SLE. Our patient presented with abdominal pain and had a 2-year history of SLE. Abdominal ultrasonography and enhanced computed tomography revealed a solid mass in the right lobe of the liver. Presumptive diagnosis of atypical hepatocellular carcinoma was made and the patient was treated with segmentectomy of S5 and S4a and cholecystectomy. The final diagnosis of UESL was made according to the pathology results. Since SLE patients may be at increased risk of malignancy, it is possible that the SLE pathogenesis may have contributed to the development of UESL in our patient. According to this case, UESL should be considered when SLE patients present with hepatic space-occupying lesions.
Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C
Authors: Ulsenheimer Axel , Paranhos-Baccalà Gláucia , Komurian-Pradel Florence , Raziorrouh Bijan , Kurktschiev Peter , Diepolder Helmut M , Zachoval Reinhart , Spannagl Michael , Jung Maria-Christina , Gruener Norbert H 
Published: September 2013

Abstract

Background
CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection.

Results
We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection. Pentamers specific for the variants were used to monitor the corresponding CD8+ T cell response. We observed outgrowth of mutations, which induced only a weak and thus potentially insufficient CD8+ T cell response. In one patient we observed outgrowth of variant epitopes with similarities to a different genotype rather than de novo mutations most probably due to a lack of responsiveness to these likely pre-existing variants. We could show that in acute hepatitis C CTL escape mutations occur much earlier than demonstrated in previous studies.

Conclusions
The adaption of the virus to a new host is characterized by a high and rapid variability in epitopes under CD8+ T cell immune pressure. This adaption takes place during the very early phase of acute infection and strikingly some sequences were reduced below the limit of detection at some time points but were detected at high frequency again at later time points. Independent of the observed variability, HCV-specific CD8+ T cell responses decline and no adaption to different or new antigens during the course of infection could be detected.
Manipulating the sleeping beauty mutase operon for the production of 1-propanol in engineered Escherichia coli
Authors: Srirangan Kajan , Akawi Lamees , Liu Xuejia , Westbrook Adam , Blondeel Eric JM , Aucoin Marc G , Moo-Young Murray , Chou C Perry 
Published: September 2013

Abstract

Background
While most resources in biofuels were directed towards implementing bioethanol programs, 1-propanol has recently received attention as a promising alternative biofuel. Nevertheless, no microorganism has been identified as a natural 1-propanol producer. In this study, we manipulated a novel metabolic pathway for the synthesis of 1-propanol in the genetically tractable bacterium Escherichia coli.

Results

E. coli strains capable of producing heterologous 1-propanol were engineered by extending the dissimilation of succinate via propionyl-CoA. This was accomplished by expressing a selection of key genes, i.e. (1) three native genes in the sleeping beauty mutase (Sbm) operon, i.e. sbm-ygfD-ygfG from E. coli, (2) the genes encoding bifunctional aldehyde/alcohol dehydrogenases (ADHs) from several microbial sources, and (3) the sucCD gene encoding succinyl-CoA synthetase from E. coli. Using the developed whole-cell biocatalyst under anaerobic conditions, production titers up to 150 mg/L of 1-propanol were obtained. In addition, several genetic and chemical effects on the production of 1-propanol were investigated, indicating that certain host-gene deletions could abolish 1-propanol production as well as that the expression of a putative protein kinase (encoded by ygfD/argK) was crucial for 1-propanol biosynthesis.

Conclusions
The study has provided a novel route for 1-propanol production in E. coli, which is subjected to further improvement by identifying limiting conversion steps, shifting major carbon flux to the productive pathway, and optimizing gene expression and culture conditions.
Analysis of the microRNA transcriptome and expression of different isomiRs in human peripheral blood mononuclear cells
Authors: Vaz Candida , Ahmad Hafiz M , Bharti Richa , Pandey Priyatama , Kumar Lalit , Kulshreshtha Ritu , Bhattacharya Alok 
Published: September 2013

Abstract

Background
MicroRNAs (miRNAs) have been recognized as one of the key regulatory non-coding RNAs that are involved in a number of basic cellular processes. miRNA expression profiling helps to identify miRNAs that could serve as biomarkers. Next generation sequencing (NGS) platforms provide the most effective way of miRNA profiling, particularly as expression of different isoforms of miRNA (IsomiRs) can be estimated by NGS. Therefore, it is now possible to discern the overall complexity of miRNA populations that participate in gene regulatory networks. It is thus important to consider different isoforms of miRNA as part of total profiling in order to understand all aspects of the biology of miRNAs.

Results
Here next generation sequencing data of small RNAs derived from normal peripheral blood mononuclear cells (PBMC) and Chronic myeloid leukemia (CML) patients has been used to generate miRNA profiles using a computation pipeline which can identify isomiRs that are natural variants of mature miRNAs. IsomiR profiles have been generated for all the 5p and 3p miRNAs (previously known as major mature miRNA and minor or miRNA*) and the data has been presented as a composite total miRNA transcriptome. The results indicated that the most abundant isomiR sequence of about 68% miRNAs, did not match the reference miRNA sequence as entered in the miRBase and that there is a definite pattern in relative concentration of different isomiRs derived from same precursors. Finally, a total of 17 potential novel miRNA sequences were identified suggesting that there are still some new miRNAs yet to be discovered.

Conclusions
Inclusion of different isoforms provides a detailed miRnome of a cell type or tissues. Availability of miRnome will be useful for finding biomarkers of different cell types and disease states. Our results also indicate that the relative expression levels of different isoforms of a miRNA are likely to be dynamic and may change with respect to changes in the cell or differentiation status.