bluuebunny/crossref_metadata_2025 huggingface dataset:
SDAR: a practical tool for graphical analysis of two-dimensional data
Authors: Weeratunga Saroja , Hu Nien-Jen , Simon Anne , Hofmann Andreas
Published: August 2012

Background

Two-dimensional data needs to be processed and analysed in almost any experimental laboratory. Some tasks in this context may be performed with generic software such as spreadsheet programs which are available ubiquitously, others may require more specialised software that requires paid licences. Additionally, more complex software packages typically require more time by the individual user to understand and operate. Practical and convenient graphical data analysis software in Java with a user-friendly interface are rare.

Results

We have developed SDAR, a Java application to analyse two-dimensional data with an intuitive graphical user interface. A smart ASCII parser allows import of data into SDAR without particular format requirements. The centre piece of SDAR is the Java class GraphPanel which provides methods for generic tasks of data visualisation. Data can be manipulated and analysed with respect to the most common operations experienced in an experimental biochemical laboratory. Images of the data plots can be generated in SVG-, TIFF- or PNG-format. Data exported by SDAR is annotated with commands compatible with the Grace software.

Conclusion

Since SDAR is implemented in Java, it is truly cross-platform compatible. The software is easy to install, and very convenient to use judging by experience in our own laboratories. It is freely available to academic users athttp://www.structuralchemistry.org/pcsb/. To download SDAR, users will be asked for their name, institution and email address. A manual, as well as the source code of the GraphPanel class can also be downloaded from this site.
Runs of homozygosity and population history in cattle
Authors: Purfield Deirdre C , Berry Donagh P , McParland Sinead , Bradley Daniel G
Published: August 2012

Background

Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes that are present in an individual due to parents transmitting identical haplotypes to their offspring. The extent and frequency of ROHs may inform on the ancestry of an individual and its population. Here we use high density (n = 777,962) bi-allelic SNPs in a range of cattle breed samples to correlate ROH with the pedigree-based inbreeding coefficients and to validate subsequent analyses using 54,001 SNP genotypes. This study provides a first testing of the inference drawn from ROH through comparison with estimates of inbreeding from calculations based on the detailed pedigree data available for several breeds.

Results

All animals genotyped on the HD panel displayed at least one ROH that was between 1–5 Mb in length with certain regions of the genome more likely to be involved in a ROH than others. Strong correlations (r = 0.75, p < 0.0001) existed between the pedigree-based inbreeding coefficient and a statistic based on sum of ROH of length > 0.5 KB and suggests that in the absence of an animal’s pedigree data, the extent of a genome under ROH may be used to infer aspects of recent population history even from relatively few samples.

Conclusions

Our findings suggest that ROH are frequent across all breeds but differing patterns of ROH length and burden illustrate variations in breed origins and recent management.
Computational prediction and validation of C/D, H/ACA and Eh_U3 snoRNAs of Entamoeba histolytica
Authors: Kaur Devinder , Gupta Abhishek Kumar , Kumari Vandana , Sharma Rahul , Bhattacharya Alok , Bhattacharya Sudha
Published: August 2012

Background

Small nucleolar RNAs are a highly conserved group of small RNAs found in eukaryotic cells. Genes encoding these RNAs are diversely located throughout the genome. They are functionally conserved, performing post transcriptional modification (methylation and pseudouridylation) of rRNA and other nuclear RNAs. They belong to two major categories: the C/D box and H/ACA box containing snoRNAs. U3 snoRNA is an exceptional member of C/D box snoRNAs and is involved in early processing of pre-rRNA. An antisense sequence is present in each snoRNA which guides the modification or processing of target RNA. However, some snoRNAs lack this sequence and often they are called orphan snoRNAs.

Results

We have searched snoRNAs ofEntamoeba histolyticafrom the genome sequence using computational programmes (snoscan and snoSeeker) and we obtained 99 snoRNAs (C/D and H/ACA box snoRNAs) along with 5 copies of Eh_U3 snoRNAs. These are located diversely in the genome, mostly in intergenic regions, while some are found in ORFs of protein coding genes, intron and UTRs. The computationally predicted snoRNAs were validated by RT-PCR and northern blotting. The expected sizes were in agreement with the observed sizes for all C/D box snoRNAs tested, while for some of the H/ACA box there was indication of processing to generate shorter products.

Conclusion

Our results showed the presence of snoRNAs inE. histolytica, an early branching eukaryote, and the structural features ofE. histolyticasnoRNAs were well conserved when compared with yeast and human snoRNAs. This study will help in understanding the evolution of these conserved RNAs in diverse phylogenetic groups.
The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes
Authors: Li Jin , Mao Nai-Ying , Zhang Chen , Yang Meng-Jie , Wang Miao , Xu Wen-Bo , Ma Xue-Jun
Published: August 2012

Background

Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens.

Methods

A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay.

Results

The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours.

Conclusions

In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.
Local decision makers’ awareness of the social determinants of health in Turkey: a cross-sectional study
Authors: Didem Evci Emine , Filiz Ergin , Orhan Okur , Gulnur Saruhan , Erdal Beser
Published: August 2012

Background

Social determinants have been described as having a greater influence than other determinants of health status. The major social determinants of health and the necessary policy objectives have been defined; it is now necessary to evaluate the effectiveness of these policies. Previous studies have shown that descriptions of the awareness level of citizens and local decision makers, practice-based research and evidence, and intersectoral studies are the best options for investigating the social determinants of health at the community level. The objective of the present study was to define local decision makers’ awareness of the social determinants of health in the Aydin province of Turkey.

Methods

A total of 53 mayors serve the Aydin city center, districts and towns. Aydin city center has 22 neighborhoods and 22 headmen responsible for them. The present study targeted all mayors and headmen in Aydin - a total of 75 possible participants. A questionnaire was used to collect the data. The questionnaire was faxed to the mayors and administered face-to-face with the headmen.

Results

Headmen identified the three most important determinants of public health as environmental issues, addictions (smoking, alcohol) and malnutrition. According to the mayors, the major determinant of public health is stress, followed by malnutrition, environmental issues, an inactive lifestyle, and the social and economic conditions of the country. Both groups expressed that the Turkish Ministry of Health, municipalities and universities are the institutions responsible for developing health policy. Headmen were found to be unaware and mayors were aware of the social determinants of health as classified by the World Health Organisation. Both groups were classified as unaware with regard to their awareness of the Marmot Review policy objectives.

Conclusions

Studies such as the present study provide important additional information on the social determinants of health, and help to increase the awareness levels of both local decision-makers and the community. Such studies must be considered a vital first step in future public health research on health determinants and their impact on national and international policies.
Mujer Mas Segura(Safer Women): a combination prevention intervention to reduce sexual and injection risks among female sex workers who inject drugs
Authors: Vera Alicia , Abramovitz Daniela , Lozada Remedios , Martinez Gustavo , Rangel M Gudelia , Staines Hugo , Patterson Thomas L , Strathdee Steffanie A
Published: August 2012

Background

Female sex workers who inject drugs (FSW-IDUs) are at risk of acquiring HIV, sexually transmitted infections (STI) and blood-borne infections through unprotected sex and sharing injection equipment. We conducted a 2×2 factorial randomized controlled trial to evaluate combination interventions to simultaneously reduce sexual and injection risks among FSW-IDUs in Tijuana and Ciudad Juarez, Mexico.

Methods/design

FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month were randomized to one of four conditions based on an a priori randomization schedule, blinding interviewer/counselors to assignment. Due to the extreme vulnerability of this population, we did not include a control group that would deny some women access to preventive information. All women received similar information regardless of group allocation; the difference was in the way the information was delivered and the extent to which women had an interactive role. Each condition was a single 60-minute session, including either an interactive or didactic version of an injection risk intervention and sexual risk intervention. Women underwent interviewer-administered surveys and testing for HIV, syphilis, gonorrhea, Chlamydia, and Trichomonas at baseline and quarterly for 12 months. Combined HIV/STI incidence will be the primary outcome. Secondary outcomes are proportionate reductions in sharing of injection equipment and unprotected sex with clients.

Discussion

Of 1,132 women, 548 (48.4%) were excluded (88.9% were ineligible; 11.1% refused to participate or did not return); 584 eligible women enrolled (284 in Tijuana; 300 in Ciudad Juarez). All 584 participants completed the baseline interview, provided biological samples and were randomized to one of the four groups. During follow-up, 17 participants (2.9%) were lost to follow-up, of whom 10 (58.8%) had died, leaving 567 participants for analysis. This study appears to be the first intervention to attempt to simultaneously reduce injection and sexual risk behaviors among FSW-IDUs. The factorial design will permit analysis to determine whether the combination of the two interactive interventions and/or its respective components are effective in reducing injection and/or sexual risks, which will have direct, tangible policy implications for Mexico and potentially other resource-poor countries.

Trial registration

NCT00840658
Periodic cohort health examinations in the TAMRISK study show untoward increases in body mass index and blood pressure during 15 years of follow-up
Authors: Kunnas Tarja , Määttä Kirsi , Palmroos Pirjo , Nikkari Seppo T
Published: August 2012

Background

Obesity is a significant risk factor for hypertension and diabetes. A cohort of 50-year-old voluntary periodic health examination (PHE) participants was analyzed 15 years retrospectively. Our aim was to evaluate changes in body mass index (BMI) and blood pressure in subjects diagnosed with hypertension and/or diabetes in comparison with healthy controls.

Methods

Voluntary periodic health examinations (PHE) of the citizens have been carried out by the city of Tampere, Finland. Health data, including body mass index (BMI) and blood pressure, were recorded every five years, starting at the age of 35 (baseline). A total of 339 subjects from the 50-year-old cohort having hypertension and/or diabetes were chosen to the study group. The control group included 604 subjects from the 50-year-old cohort who had the same follow-up information but were not diagnosed with hypertension and/or diabetes.

Results

In the study group the mean BMI had increased from 26.1 at baseline to 28.5 at the final 15-year follow-up examination. The corresponding increase in the control group was from 23.8 at baseline to 25.5 at the final follow-up. The difference in change with time between the groups was statistically significant (p = 0.04). On the average, the controls gained 4.9 kilograms, whereas subjects in the study group gained 7.0 kilograms over the 15 years of follow-up. Systolic and diastolic blood pressures were also higher in the study group already at baseline and systolic blood pressure increased with time more in the study group than in the control group (p = 0.004).

Conclusions

BMI and blood pressure were higher in the study group in comparison with the controls already at baseline at 35 years, and the differences were not favorably changed during the follow-up. Apparently, the effect of PHE had not been as efficient as planned on subjects in the study group, who were already slightly overweight at baseline.
Comparison of efficacy of different route of administration of chemotherapy on unresectable, advanced gastric cancer
Authors: Zhang Caihua , Li Guoli , Fan Chaogang , Xu Jian , Cao Jianmin , Liu Shen , Li Ning
Published: August 2012

Background

The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer.

Methods

A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared.

Results

In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P < 0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups.

Conclusions

For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.
Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis
Authors: Fissolo Nicolás , Costa Carme , Nurtdinov Ramil N , Bustamante Marta F , Llombart Victor , Mansilla María J , Espejo Carmen , Montalban Xavier , Comabella Manuel
Published: August 2012

Background

DNA vaccines represent promising therapeutic strategies in autoimmune disorders such as multiple sclerosis (MS). However, the precise mechanisms by which DNA vaccines induce immune regulation remain largely unknown. Here, we aimed to expand previous knowledge existing on the mechanisms of action of DNA vaccines in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), by treating EAE mice with a DNA vaccine encoding the myelin oligodendrocyte glycoprotein (MOG), and exploring the therapeutic effects on the disease-induced inflammatory and neurodegenerative changes.

Methods

EAE was induced in C57BL6/J mice by immunization with MOG35-55 peptide. Mice were intramuscularly treated with a MOG-DNA vaccine or vehicle in prophylactic and therapeutic approaches. Histological studies were performed in central nervous system (CNS) tissue. Cytokine production and regulatory T cell (Treg) quantification were achieved by flow cytometry. Gene expression patterns were determined using microarrays, and the main findings were validated by real-time PCR.

Results

MOG-DNA treatment reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Suppression of clinical EAE was associated with dampening of antigen (Ag)-specific proinflammatory Th1 and Th17 immune responses and, interestingly, expansion of Treg in the periphery and upregulation in the CNS of genes encoding neurotrophic factors and proteins involved in remyelination.

Conclusions

These results suggest for the first time that the beneficial effects of DNA vaccines in EAE are not limited to anti-inflammatory mechanisms, and DNA vaccines may also exert positive effects through hitherto unknown neuroprotective mechanisms.
Small duct autoimmune sclerosing cholangitis and Crohn colitis in a 10-year-old child. A case report and review of the literature
Authors: Larsen Erling Peter , Bayat Allan , Vyberg Mogens
Published: August 2012

Autoimmune sclerosing cholangitis is an overlap syndrome characterized by features of both autoimmune hepatitis and primary sclerosing cholangitis, the latter usually involving the large bile ducts. Autoimmune sclerosing cholangitis occurs more often in children than in adults and is frequently associated with inflammatory bowel disease, predominantly ulcerative colitis. We report a unique case of a 10-year-old Danish boy with severe small duct autoimmune sclerosing cholangitis and synchronic Crohn colitis. He was referred with a history of weight loss, abdominal pain, vomiting and diarrhea. Biochemical anomalies included elevated alanine aminotransferase, γ-glutamyl transferase and immunoglobulin G levels and the presence of smooth muscle antibodies and perinuclear antineutrophil cytoplasmic antibodies but normal alkaline phosphatase. Liver biopsy specimen revealed features of both autoimmune hepatitis and sclerosing cholangitis, the latter characterized by acute, hyperplastic and destructive inflammation – granulocytic epithelial lesion – of the small ducts. Magnetic resonance cholangiography was normal. Colonoscopic biopsies showed chronic inflammatory changes of the caecum and the ascending and transverse colon compatible with Crohn disease. Ursodeoxycholic acid and immunosuppressive treatment was initiated and within four weeks of treatment the general condition improved. Normalization of aminotransferase was seen at 21 weeks and γ-glutamyl transferase at 72 weeks after first admittance, while immunoglobulin G remained slightly increased.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1418596609736470
Synthesis and preliminary in vivo evaluations of polyurethane microstructures for transdermal drug delivery
Authors: Borcan Florin , Soica Codruta M , Ganta Srinivas , Amiji Mansoor M , Dehelean Cristina A , Munteanu Melania F
Published: August 2012

Background

Polymers have been considered as important materials in fabrication of microstructures for various medical purposes including drug delivery. This study evaluates polyurethane as material for hollow microstructures preparation.

Results

Polyurethane microstructures were obtained by interfacial polyaddition combined with spontaneous emulsification and present slightly acid pH values. Scanning electron microscopy revealed the existence of irregular shapes and agglomerated microstructures. The material is heat resistant up to 280°C. Good results were recorded on murine skin tests in case of polyurethane microstructures based on isophorone diisocyanate. Mesenchymal stem cells viability presents good results for the same sample after 48 hours based on the Alamar Blue test.

Conclusions

The research revealed the reduced noxiousness of this type of microstructures and consequently the possibility of their use for therapeutic purposes.
A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis
Authors: Zheng Shuqiu , Ghitani Nima , Blackburn Jessica S , Liu Jeh-Ping , Zeitlin Scott O
Published: August 2012

Background

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ) stretch within Huntingtin (htt), the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR) in modulating HD mouse model pathogenesis is currently unknown.

Results

We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh) encoding N-terminal hemaglutinin (HA) or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt) and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt). Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q) htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis.

Conclusion

In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.
The international effort: building the bridge for Translational Medicine: Report of the 1st International Conference of Translational Medicine (ICTM)
Authors: Chen Xiaoming , Andersson Roland , Cho William CS , Christiani David , Coico Richard , Drazen Jeffery , Ege Markus , Fehniger Thomas , Gao Hongwei , Jin Kunlin , Liebman Michael N , Lopez Elena , Marraro Giuseppe , Marko‐Varga Gyorgy , Marincola Francesco M , Popescu Laurentiu M , Spada Claudio , Shahzad Aamir , Wang Ena , Wang Wei , Wang Xiangdong , Wang Yong‐Xiao , Xia Jinglin , Qu Jia
Published: August 2012

Background

Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad.

Findings

The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two‐way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation.

Conclusions

It was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two‐fold: to accelerate the two‐way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state‐of‐art translational research and salient aspects of the ensuing discussions.
Precision medicine: an approach to R&D for delivering superior medicines to patients
Authors: Dolsten Mikael , Søgaard Morten
Published: August 2012

Pharmaceutical R&D productivity has declined over the last decade despite increasing investments. Recent trends, however, indicate a potential reversal of this trend fueled by a wave of new biologics, vaccines and highly selective NCEs directed against targets validated by human genetics, focus on new disease areas including orphan and genetic diseases and more precise tailoring of medicines to their target populations.
Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
Authors: Abdulahad Deena A , Westra Johanna , Bijzet Johannes , Dolff Sebastian , van Dijk Marcory C , Limburg Pieter C , Kallenberg Cees GM , Bijl Marc
Published: August 2012

Introduction

Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity.

Methods

The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies.

Results

Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4.

Conclusion

Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation.
Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease
Authors: De Palma G , Kamanova J , Cinova J , Olivares M , Drasarova H , Tuckova L , Sanz Y
Published: August 2012

Bifidobacteria and enterobacteria influence phenotypic and functional maturation of DCs differently, which together with gliadin, could define the role of DCs in celiac disease progression.

DC maturation and functions are influenced by microbial and environmental stimuli, which could contribute to immune dysfunction. Here, we have investigated the role of enterobacteria (Escherichia coli CBL2 and Shigella CBD8) isolated from CD patients, bifidobacteria (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), and gliadins on phenotypic and functional features of MDDCs and in coculture with Caco-2 cells. The ultimate goal of our study is to understand the roles played by specific components of the gut microbiota in CD. Enterobacteria induced marked alterations in MDDC morphology, inducing podosome dissolution and dendrites, and activated MDDC adhesion and spreading. Enterobacteria also induced inflammatory cytokine production (IFN-γ, TNF-α, and IL-12), partially resembling the gliadin-induced Th1-type cytokine profile. B. longum CECT 7347 and B. bifidum CECT 7365 induced minor MDDC morphological changes and activated adhesion and spreading and inflammatory cytokine production to a lesser extent compared with enterobacteria. B. longum CECT 7347 also induced lower CD86 and CD40 expression on MDDCs than the two enterobacteria. The aforementioned bifidobacterial strain also reduced gliadin-induced IFN-γ production and increased IL-10 secretion when both stimuli were combined. Similar trends were detected for MDDCs cocultured with Caco-2 cells. B. longum CECT 7347 reversed the gliadin-reduced ZO-1 expression in Caco-2 cells. Thus, our results suggest that specific components of the gut microbiota may influence phenotypic and functional maturation of DCs differently and their interactions with epithelial cells. This could ultimately define the role of DCs in CD progression.
Figural Interpretation as Modernist Hermeneutics: The Rhetoric of Erich Auerbach'sMimesis
Authors: Hovind Jacob
Published: August 2012

If Erich Auerbach's Mimesis is generally considered a landmark in twentieth-century literary criticism and an originary text for the modern practice of comparative literature, then this is despite the fact that its profound interpretive structures and hermeneutic consequences still remain to be truly read. This essay proposes that there is a complex theory of reading to be found in Mimesis and that it is one of the most exemplary models of literary hermeneutics in modern criticism. To discern this theory of reading, however, one must go against the dominant tendency in recent critical readings of Mimesis. This tendency, originating in the work of Edward Said and practiced in some form or another by nearly all of Auerbach's critics of the last three decades, is to contextualize the writing of Mimesis and to explain its seemingly ungainly form in terms of the specific particularities of the time and place of the work's composition. What Auerbach famously called the “incomparable historical vantage point” of his exile in Istanbul, these critics argue, has inextricably shaped the contours of his work as a critic.

This essay suggests that focusing on exile as Auerbach's most important legacy avoids the real work of reading Mimesis and the interpretive strategies it contains, and that such a reading requires bracketing the historical conditions of his work's composition, a story with an easy appeal to pathos. To truly discern the significance of Auerbach's contribution to our field, one must first and foremost read him reading. This essay attempts to demonstrate three essentially interrelated points that might begin to salvage Auerbach's criticism from its obscured place in the literary critical canon. The first of these points is that throughout his entire corpus Auerbach does in fact construct a specific method for literary understanding. Second, this hermeneutics stems from his decades-long preoccupation with figural interpretation, the essentially Christian mode of reading that he traces from late Roman antiquity through the Middle Ages. Third, there emerges out of his “figural hermeneutics” a thoroughly modernist critical point of view, one whose understanding of mimesis depends upon the structure of figural understanding rather than any naïve doctrine of literary realism. Mimesis, as it gradually emerges out of Auerbach's hermeneutics, is a figure of language.
Between Theory and Reality: Cosmopolitanism of Nodal Cities in Paweł Huelle'sCastorp
Authors: Spyra Ania
Published: August 2012

The study of the literature of large metropolitan centers that are divided along linguistic, ethnic, and cultural fault lines by colonizations, redrawn borders, or waves of migration provides one alternative to the national model in the study of comparative literature. Often opposed to nationalism in all its guises, the literature of nodal cities is strongly aligned with the idealistic goals of cosmopolitanism and Goethean Weltliteratur in emphasizing the fluidity of borders in those spaces and the complexity of identities they engender. The Polish novelist Paweł Huelle's 2004 novel Castorp centers on one such nodal city, Danzig/Gdańsk, in order to respond to Thomas Mann's meditation on cosmopolitanism in The Magic Mountain. Castorp is also a postcolonial response to the canonical German text; it calls for rememorizing and reimagining the presence of German history in the Polish landscape. Drawing on Jacques Derrida's On Cosmopolitanism and Forgiveness, this article argues that the postcolonial perspective of Castorp offers not an accusation but a call for a cosmopolitan reconciliation and inclusiveness. Huelle does not provide a nationalist re-reading of the past, but a complex review of overlapping identities that cannot be reduced to a simplistic German-Polish dialectic. Rather than writing back in the sense of striking back, Huelle invites us to understand his city in a “deep time” — to use Wai Chi Dimock's phrase — that includes, rather than erases, its German past.
EpiCentro: The Emergence of a New Central American-American Literature
Authors: Arias Arturo
Published: August 2012

This article explores the emergence of Central American-American discursive and performance poetic art that, written bilingually and occasionally incorporating Portuguese or an indigenous language, has been present in the United States since the mid-1980s, but bloomed in the first decade of the twenty-first century. It analyzes three of the poems in the EpiCentro anthology — by Gustavo Guerra Vásquez, Karina Alvarado, and Marlon Morales — that have in common multiple and ongoing negotiations and renegotiations of identity, compounding a fusionary process that problematizes traditional identities associated with Latinoness and questions the stability of this very concept, changing in the process fundamental assumptions about the field. It also explores the work and impact of Maya Chinchilla, one of the founders of the group and editor of the anthology. The article attempts to place the anthology within what Aníbal Quijano has called the “coloniality of power,” a term deployed to move thinking beyond Western and Eurocentric conceptualizations. This approach provides a new way of framing the issues of cultural production and agency in order to transcend identities originally associated with any given Latin American nation-state. It is a reminder that we need to seek alternative epistemologies that encompass newer approaches to our understanding of the flux of Latin American diasporas to and within the U.S. We can no longer conceive of Latinidad as a trope under which hyphenated nationalities seek refuge, in a side-by-side nature, from the racist storm of white Christian fundamentalism, without losing their singular self-defining traits.
The Injured World: Intersex and the Phenomenology of Feeling
Authors: Morland Iain
Published: August 2012

In debates about the medical management of intersex, also known as “disorders of sex development,” it is often assumed that morally good treatment can make patients, families, and doctors feel comfortable and, conversely, that morally bad treatment generates feelings of discomfort. Commentators and stakeholders diverge over definitions of good and bad treatment, but everyone wants to feel comfortable—whether with sexually ambiguous anatomies, infant genital surgery, the identity “intersex,” or the nomenclature of “disorders of sex development.” This multidisciplinary article critically analyzes the role of feelings in such debates. It argues against accounts of “lived experience” that cast feelings as purely personal, to focus instead on interpersonal feelings between individuals with and without intersex anatomies and with and without histories of genital surgery. The article draws on neuroscience and philosophy to reinterpret such interpersonal feelings as occasions when individuals who have not had surgery literally feel on behalf of those who have, in particular where surgery has caused desensitizing nerve damage. This phenomenon can be understood neuroscientifically as sensations referred between bodies by mirror neurons and philosophically as an injury to the flesh of the world of which we are all composed.
Blindness and Animality, or Learning How to Live Finally in Clarice Lispector’s The Passion according to G. H.
Authors: Goh Irving
Published: August 2012

Clarice Lispector’s The Passion according to G. H. (1964) takes up the themes of animality and blindness as modes of thinking and living beyond the limits of subjectivity. While the notion of animality was subsequently explored by Gilles Deleuze and Félix Guattari in Mille plateaux and Jacques Derrida in L’animal que donc je suis, Derrida in Mémoires d’aveugle, Hélène Cixous in Écrire aveugle, and Jean-Luc Nancy in Tombe de sommeil were experimenting with the theme of blindness and the rejection of sight. This article argues that Lispector—before poststructuralist thinkers began to write about such themes—brings animality and blindness together to open a way toward learning how to live finally, that is, living without the constraints of external determination and beyond the delimitations of preconceived subjectivity.
Medical politician and man of Olympian vision and energy: Dr William Penny Brookes (1809–95) of Much Wenlock
Authors: Connor Henry
Published: August 2012

William Penny Brookes lived all his life in Much Wenlock in Shropshire where he worked as a general practitioner for 60 years. He is now best remembered as the founder of the Wenlock Olympian Society, as a founding member of the first national Olympian association and for his influence on Baron Pierre de Coubertin, the founder of the modern Olympic movement. He was a tireless campaigner for the introduction of physical education and a lessening of the academic workload in elementary schools. He was also an important figure in the medical reform movement of the mid-19th century. In Much Wenlock he was a much respected philanthropist and was involved in many civic activities. He was also a notable botanist and antiquarian.
Willem J Kolff (1911–2009): physician, inventor and pioneer: father of artificial organs
Authors: Morrissey Megan
Published: August 2012

Medical pioneer Willem Johan Kolff was an inspirational father, son, physician and inventor. He founded the development of the first kidney dialysis machine, pioneered advances in the heart and lung machine, laid down the foundations for the first mainland blood bank in Europe and successfully implanted the first artificial heart into humans.
Baron Coubertin (1863–1937) and the Olympic cult of health
Authors: Biddiss Michael
Published: August 2012

This paper reviews the career of Baron Coubertin and highlights how his campaign for a modernizing revival of the spirit of ancient Olympic contests brought him into often adversarial contact with the medical establishment of his era.
Lionel Charles Renwick (Rennick) Emmett (1913–96): physician and Olympian
Authors: Biswas Tamoghna , Datta Adrija , Chandra Shivika
Published: August 2012

Lionel Charles Renwick Emmett, a physician who trained in pre-independent India as a medical student, participated in the 1936 Berlin Summer Olympics as a part of the Indian field hockey team that won the Gold Medal.
The Escherichia coli RlmN methyltransferase is a dual-specificity enzyme that modifies both rRNA and tRNA and controls translational accuracy
Authors: Benítez-Páez Alfonso , Villarroya Magda , Armengod M.-Eugenia
Published: August 2012

Modifying RNA enzymes are highly specific for substrate—rRNA or tRNA—and the target position. In Escherichia coli, there are very few multisite acting enzymes, and only one rRNA/tRNA dual-specificity enzyme, pseudouridine synthase RluA, has been identified to date. Among the tRNA-modifying enzymes, the methyltransferase responsible for the m2A synthesis at purine 37 in a tRNA set still remains unknown. m2A is also present at position 2503 in the peptidyl transferase center of 23S RNA, where it is introduced by RlmN, a radical S-adenosyl-L-methionine (SAM) enzyme. Here, we show that E. coli RlmN is a dual-specificity enzyme that catalyzes methylation of both rRNA and tRNA. The ΔrlmN mutant lacks m2A in both RNA types, whereas the expression of recombinant RlmN from a plasmid introduced into this mutant restores tRNA modification. Moreover, RlmN performs m2A37 synthesis in vitro using a tRNA chimera as a substrate. This chimera has also proved useful to characterize some tRNA identity determinants for RlmN and other tRNA modification enzymes. Our data suggest that RlmN works in a late step during tRNA maturation by recognizing a precise 3D structure of tRNA. RlmN inactivation increases the misreading of a UAG stop codon. Since loss of m2A37 from tRNA is expected to produce a hyperaccurate phenotype, we believe that the error-prone phenotype exhibited by the ΔrlmN mutant is due to loss of m2A from 23S rRNA and, accordingly, that the m2A2503 modification plays a crucial role in the proofreading step occurring at the peptidyl transferase center.
Upregulation of hepatic LRP1 by rosiglitazone: a possible novel mechanism of the beneficial effect of thiazolidinediones on atherogenic dyslipidemia
Authors: Moon Jae Hoon , Kim Hyung Jun , Kim Hyun Min , Yang Ae Hee , Lee Byung-Wan , Kang Eun Seok , Lee Hyun Chul , Cha Bong Soo
Published: August 2012

Hepatic LDL receptor-related protein 1 (LRP1) plays a role in the clearance of circulating remnant lipoproteins. In this study, we investigated the effect of rosiglitazone treatment on the expression and function of hepatic LRP1. HepG2 cells were incubated with various concentrations of rosiglitazone. Male Long-Evans Tokushima Otsuka (LETO) rats and Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats were treated with rosiglitazone for 5 weeks. The expression and function of LRP1 in HepG2 cells and liver samples of rats were analyzed. LRP1 mRNA and protein expressions were increased by 0.5 and 5 μM rosiglitazone in HepG2 cells. However, at concentrations above 50 μM rosiglitazone, LRP1 mRNA and protein expressions did not change compared with those in nontreated cells. Reporter assay showed that 0.5 and 5 μM rosiglitazone increased the transcriptional activity of theLRP1promoter in HepG2 cells. The uptake of apolipoprotein E through LRP1 in HepG2 cells was also increased by rosiglitazone. Hepatic LRP1 was reduced in OLETF rats compared with that of LETO rats and rosiglitazone treatment increased hepatic LRP1 in OLETF rats. A high glucose condition (25 mM glucose in culture media) reduced the expression of LRP1 in HepG2 cells, and this reduced LRP1 expression was recovered with rosiglitazone. In conclusion, our data suggest that decreased hepatic LRP1 in a diabetic condition is associated with the development of atherogenic dyslipidemia and that increased hepatic LRP1 by thiazolidinediones could contribute to an improvement in atherogenic lipid profiles in diabetic patients.
Acute Poststreptococcal Glomerulonephritis: A Manifestation of Immune Reconstitution Inflammatory Syndrome
Authors: Martin Julie , Kaul Aditya , Schacht Robert
Published: August 2012

Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication of initiation of highly active antiretroviral therapy in HIV-infected patients. As the immune system recovers, an inappropriate inflammatory response often occurs that causes significant disease. It is most commonly seen in patients naïve to therapy with CD4+ T-lymphocyte counts <100 cells/cmm and usually presents as a flare of mycobacterial, cytomegalovirus, or herpes zoster infections. Less commonly, this syndrome occurs in response to noninfectious triggers and results in autoimmune or malignant disease. Here we present the first case of acute poststreptococcal glomerulonephritis associated with varicella zoster virus and IRIS in an adolescent with perinatally acquired HIV and hepatitis C virus infections. Our patient was not naïve to therapy but was starting a new regimen of therapy because of virologic failure and had a relatively high CD4+ T-lymphocyte count. This case report indicates that IRIS remains a concern after initiation of a new highly active antiretroviral therapy regimen in HIV-infected patients with high viral loads, even in the presence of CD4+ T-lymphocyte counts >100 cells/cmm. It may present as infectious, malignant, or autoimmune conditions including poststreptococcal glomerulonephritis.