bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion
Authors: Zheng Dongling , Kille Peter , Feeney Graham P , Cunningham Phil , Handy Richard D , Hogstrand Christer
Published: June 2012

Background

Zinc deficiency is detrimental to organisms, highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within the zebrafish gill. This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals.

Results

Zebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array. Of the genes represented the expression of a total of 333 transcripts showed differential regulation by zinc depletion (having a fold-change greater than 1.8 and an adjusted P-value less than 0.1, controlling for a 10% False Discovery Rate). Down-regulation was dominant at most time points and distinct sets of genes were regulated at different stages. Annotation enrichment analysis revealed that 'Developmental Process' was the most significantly overrepresented Biological Process GO term (P = 0.0006), involving 26% of all regulated genes. There was also significant bias for annotations relating to development, cell cycle, cell differentiation, gene regulation, butanoate metabolism, lysine degradation, protein tyrosin phosphatases, nucleobase, nucleoside and nucleotide metabolism, and cellular metabolic processes. Within these groupings genes associated with diabetes, bone/cartilage development, and ionocyte proliferation were especially notable. Network analysis of the temporal expression profile indicated that transcription factors foxl1, wt1, nr5a1, nr6a1, and especially, hnf4a may be key coordinators of the homeostatic response to zinc depletion.

Conclusions

The study revealed the complex regulatory pathways that allow the organism to subtly respond to the low-zinc condition. Many of the processes affected reflected a fundamental restructuring of the gill epithelium through reactivation of developmental programs leading to stem cell differentiation. The specific regulation of genes known to be involved in development of diabetes provides new molecular links between zinc deficiency and this disease. The present study demonstrates the importance of including the time-dimension in microarray studies.
Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth
Authors: Bolpetti Aline , Silva João S , Villa Luisa L , Lepique Ana Paula
Published: June 2012

Background

Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth.

Results

TC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes.

Conclusions

Our data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.
Filifactor alocis - involvement in periodontal biofilms
Authors: Schlafer Sebastian , Riep Birgit , Griffen Ann L , Petrich Annett , Hübner Julia , Berning Moritz , Friedmann Anton , Göbel Ulf B , Moter Annette
Published: June 2012

Background

Bacteria in periodontal pockets develop complex sessile communities that attach to the tooth surface. These highly dynamic microfloral environments challenge both clinicians and researchers alike. The exploration of structural organisation and bacterial interactions within these biofilms is critically important for a thorough understanding of periodontal disease. In recent years, Filifactor alocis, a fastidious, Gram-positive, obligately anaerobic rod was repeatedly identified in periodontal lesions using DNA-based methods. It has been suggested to be a marker for periodontal deterioration. The present study investigated the epidemiology of F. alocis in periodontal pockets and analysed the spatial arrangement and architectural role of the organism in in vivo grown subgingival biofilms.

Results

A species-specific oligonucleotide probe, FIAL, was designed and evaluated. A total of 490 subgingival plaque samples were submitted to PCR and subsequent dot blot hybridization to compare the prevalence of F. alocis in patients suffering from generalized aggressive periodontitis (GAP), chronic periodontitis (CP), and control subjects resistant to periodontitis. Moreover, a specially designed carrier system was used to collect in vivo grown subgingival biofilms from GAP patients. Subsequent topographic analysis was performed using fluorescence in situ hybridization.

While the majority of patients suffering from GAP or CP harboured F. alocis, it was rarely detected in the control group. In the examined carrier-borne biofilms the organism predominantly colonized apical parts of the pocket in close proximity to the soft tissues and was involved in numerous structures that constitute characteristic architectural features of subgingival periodontal biofilms.

Conclusions

F. alocis is likely to make a relevant contribution to the pathogenetic structure of biofilms accounting for periodontal inflammation and can be considered an excellent marker organism for periodontal disease.
Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices
Authors: Gágyor Ildikó , Hummers-Pradier Eva , Kochen Michael M , Schmiemann Guido , Wegscheider Karl , Bleidorn Jutta
Published: June 2012

Background

Uncomplicated urinary tract infections (UTI) are usually treated with antibiotics as recommended by primary care guidelines. Antibiotic treatment supports clinical cure in individual patients but also leads to emerging resistance rates in the population. We designed a comparative effectiveness study to investigate whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen, reserving antibiotic treatment to patients who return due to ongoing or recurrent symptoms.

Methods/design

This is a randomized-controlled, double-blind, double dummy multicentre trial assessing the comparative effectiveness of immediate vs. conditional antibiotic therapy in uncomplicated UTI. Women > 18 and < 65 years, presenting at general practices with at least one of the typical symptoms dysuria or frequency/urgency of micturition, will be screened and enrolled into the trial. During an 18- months recruitment period, a total of 494 patients will have to be recruited in 45 general practices in Lower Saxony. Participating patients receive either immediate antibiotic therapy with fosfomycin-trometamol 1x3g or initial symptomatic treatment with ibuprofen 3x400mg for 3 days. The ibuprofen group will be provided with antibiotic therapy only if needed, i.e. for persistent or worsening symptoms. For a combined primary endpoint, we choose the number of all antibiotic prescriptions regardless of the medical indication day 0–28 and the “disease burden”, defined as a weighted sum of the daily total symptom scores from day 0 to day 7. The study is considered positive if superiority of conditional antibiotic treatment with respect to the first primary endpoint and non-inferiority of conditional antibiotic treatment with respect to the second primary endpoint is proven.

Discussion

This study aims at investigating whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen. The comparative effectiveness design was chosen to prove the effectiveness of two therapeutic strategies instead of the pure drug efficacy.

Trial registration

Clinicaltrials.Gov: NCT01488955
Huntington's Disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database
Authors: Kalathur Ravi Kiran Reddy , Hernández-Prieto Miguel A , Futschik Matthias E
Published: June 2012

Background

Huntington’s disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner.

Methods

To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies.

Results

Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B).

Conclusions

The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics.
Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and ca125 in predicting epithelial ovarian cancer: A meta-analysis
Authors: Li Fake , Tie Ruxiu , Chang Kai , Wang Feng , Deng Shaoli , Lu Weiping , Yu Lili , Chen Ming
Published: June 2012

Backgrounds

Risk for Ovarian Malignancy Algorithm (ROMA) and Human epididymis protein 4 (HE4) appear to be promising predictors for epithelial ovarian cancer (EOC), however, conflicting results exist in the diagnostic performance comparison among ROMA, HE4 and CA125.

Methods

Remote databases (MEDLINE/PUBMED, EMBASE, Web of Science, Google Scholar, the Cochrane Library and ClinicalTrials.gov) and full texts bibliography were searched for relevant abstracts. All studies included were closely assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). EOC predictive value of ROMA was systematically evaluated, and comparison among the predictive performances of ROMA, HE4 and CA125 were conducted within the same population. Sensitivity, specificity, DOR (diagnostic odds ratio), LR ± (positive and negative likelihood ratio) and AUC (area under receiver operating characteristic-curve) were summarized with a bivariate model. Subgroup analysis and sensitivity analysis were used to explore the heterogeneity.

Results

Data of 7792 tests were retrieved from 11 studies. The overall estimates of ROMA for EOC predicting were: sensitivity (0.89, 95% CI 0.84-0.93), specificity (0.83, 95% CI 0.77-0.88), and AUC (0.93, 95% CI 0.90-0.95). Comparison of EOC predictive value between HE4 and CA125 found, specificity: HE4 (0.93, 95% CI 0.87-0.96) > CA125 (0.84, 95% CI 0.76-0.90); AUC: CA125 (0.88, 95% CI 0.85-0.91) > HE4 (0.82, 95% CI 0.78-0.85). Comparison of OC predictive value between HE4 and CA125 found, AUC: CA125 (0.89, 95% CI 0.85-0.91) > HE4 (0.79, 95% CI 0.76-0.83). Comparison among the three tests for EOC prediction found, sensitivity: ROMA (0.86, 95%CI 0.81-0.91) > HE4 (0.80, 95% CI 0.73-0.85); specificity: HE4 (0.94, 95% CI 0.90-0.96) > ROMA (0.84, 95% CI 0.79-0.88) > CA125 (0.78, 95%CI 0.73-0.83).

Conclusions

ROMA is helpful for distinguishing epithelial ovarian cancer from benign pelvic mass. HE4 is not better than CA125 either for EOC or OC prediction. ROMA is promising predictors of epithelial ovarian cancer to replace CA125, but its utilization requires further exploration.
A survey on clinical presentation and nutritional status of infants with suspected cow' milk allergy
Authors: Vieira Mário C , Morais Mauro B , Spolidoro José VN , Toporovski Mauro S , Cardoso Ary L , Araujo Gabriela TB , Nudelman Victor , Fonseca Marcelo CM
Published: June 2012

Background

Cow's milk is the most common food allergen in infants and the diagnosis of cow's milk allergy is difficult, even with the use of several diagnostic tests. Therefore, elimination diets and challenge tests are essential for the diagnosis and treatment of this disorder. The aim of this study is to report the clinical presentation and nutritional status of children evaluated by pediatric gastroenterologists for the assessment of symptoms suggestive of cow's milk allergy.

Methods

An observational cross-sectional study was performed among 9,478 patients evaluated by 30 pediatric gastroenterologists for 40 days in 5 different geographical regions in Brazil. Clinical data were collected from patients with symptoms suggestive of cow's milk allergy. The nutritional status of infants (age ≤ 24 months) seen for the first time was evaluated according to z-scores for weight-for-age, weight-for-height, and height-for-age. Epi-Info (CDC-NCHS, 2000) software was used to calculate z-scores.

Results

The prevalence of suspected cow's milk allergy in the study population was 5.4% (513/9,478), and the incidence was 2.2% (211/9,478). Among 159 infants seen at first evaluation, 15.1% presented with a low weight-for-age z score (< -2.0 standard deviation - SD), 8.7% with a low weight-for-height z score (< -2.0 SD), and 23.9% with a low height-for-age z score (< -2.0 SD).

Conclusion

The high prevalence of nutritional deficits among infants with symptoms suggestive of cow's milk allergy indicates that effective elimination diets should be prescribed to control allergy symptoms and to prevent or treat malnutrition.
Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol
Authors: Gómez-Marcos Manuel A , Recio-Rodríguez José I , Rodríguez-Sánchez Emiliano , Castaño-Sánchez Yolanda , de Cabo-Laso Angela , Sánchez-Salgado Benigna , Rodríguez-Martín Carmela , Castaño-Sánchez Carmen , Gómez-Sánchez Leticia , García-Ortiz Luis
Published: June 2012

Background

Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.

The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome.

Methods/Design

Design: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up.

Setting: The study will be carried out in the urban primary care setting.

Study population: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included.

Measurements: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs.

Discussion

The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.

Trial Registration

ClinicalTrials.gov Identifier: NCT01065155
Effect of scheduled monitoring of liver function during anti-Tuberculosis treatment in a retrospective cohort in China
Authors: Wu Shanshan , Xia Yinyin , Lv Xiaozhen , Zhang Yuan , Tang Shaowen , Yang Zhirong , Tu Dehua , Deng Peiyuan , Cheng Shiming , Wang Xiaomeng , Yuan Yanli , Liu Feiying , Hu Daiyu , Zhan Siyan
Published: June 2012

Background

Data on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment.

Methods

A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis.

Results

33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001).

Conclusions

Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.
Unintentional injury mortality in India, 2005: Nationally representative mortality survey of 1.1 million homes
Authors: Jagnoor Jagnoor , Suraweera Wilson , Keay Lisa , Ivers Rebecca Q , Thakur JS , Jha Prabhat ,   Million Death Study Collaborators
Published: June 2012

Background

Unintentional injuries are an important cause of death in India. However, no reliable nationally representative estimates of unintentional injury deaths are available. Thus, we examined unintentional injury deaths in a nationally representative mortality survey.

Methods

Trained field staff interviewed a living relative of those who had died during 2001-03. The verbal autopsy reports were sent to two of the130 trained physicians, who independently assigned an ICD-10 code to each death. Discrepancies were resolved through reconciliation and adjudication. Proportionate cause specific mortality was used to produce national unintentional injury mortality estimates based on United Nations population and death estimates.

Results

In 2005, unintentional injury caused 648 000 deaths (7% of all deaths; 58/100 000 population). Unintentional injury mortality rates were higher among males than females, and in rural versus urban areas. Road traffic injuries (185 000 deaths; 29% of all unintentional injury deaths), falls (160 000 deaths, 25%) and drowning (73 000 deaths, 11%) were the three leading causes of unintentional injury mortality, with fire-related injury causing 5% of these deaths. The highest unintentional mortality rates were in those aged 70years or older (410/100 000).

Conclusions

These direct estimates of unintentional injury deaths in India (0.6 million) are lower than WHO indirect estimates (0.8 million), but double the estimates which rely on police reports (0.3 million). Importantly, they revise upward the mortality due to falls, particularly in the elderly, and revise downward mortality due to fires. Ongoing monitoring of injury mortality will enable development of evidence based injury prevention programs.
The efficacy and tolerability of artemisinin-piperaquine (Artequick®) versus artesunate-amodiaquine (Coarsucam™) for the treatment of uncomplicated Plasmodium falciparum malaria in south-central Vietnam
Authors: Thanh Nguyen Xuan , Trung Trieu Nguyen , Phong Nguyen Chinh , Quang Huynh Hong , Dai Bui , Shanks G Dennis , Chavchich Marina , Edstein Michael D
Published: June 2012

Background

In Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria. However, limited efficacy and tolerability data are available on alternative forms of ACT in Vietnam in case there is a reduction in the susceptibility of dihydroartemisinin-piperaquine. A study was conducted to compare the efficacy and tolerability of two fixed-dose formulations of ACT, artemisinin–piperaquine (Artequick®, ARPQ) and artesunate-amodiaquine (Coarsucam™, ASAQ) for the treatment of P. falciparum malaria in south-central Vietnam.

Methods

A randomized, open-label trial was conducted comparing the efficacy of a two-day regimen of ARPQ (~2.8 mg/kg artemisinin plus ~17.1 mg/kg of piperaquine per day) and a three-day regimen of ASAQ (~4.7 mg/kg of artesunate plus ~12.6 mg/kg of amodiaquine per day) for the treatment of children and adults with uncomplicated falciparum malaria. Primary efficacy endpoint was day 42, PCR-corrected, parasitological cure rate. Secondary endpoints were parasite and fever clearance times and tolerability.

Results

Of 128 patients enrolled, 63 were administered ARPQ and 65 ASAQ. Of the patients who completed the 42 days follow-up period or had a recurrence of malaria, 55 were on ARPQ (30 children, 25 adults) and 59 were on ASAQ (31 children, 28 adults). Recrudescent parasitaemia was PCR-confirmed for one patient in each treatment group, with cure rates at day 42 of 98% (95% CI: 88–100) for both forms of ACT. The median parasite clearance time was significantly slower in the ARPQ group compared with the ASAQ group (48 h vs. 36 h, P<0.001) and fever clearance times were shorter in the ASAQ group (12 h vs. 24 h, P = 0.07). The two forms of ACT were well tolerated with no serious adverse events.

Conclusion

Both forms of ACT were highly efficacious in the treatment of uncomplicated P. falciparum malaria. Although the two-day course of ARPQ was equally as effective as the three-day course of ASAQ, parasite and fever clearance times were shorter with ASAQ. Further studies are warranted in different regions of Vietnam to determine the nationwide efficacy of ASAQ.

Trial registration

Australian New Zealand Clinical Trials Registry Number, ACTRN12609000816257
Protein surface representation and analysis by dimension reduction
Authors: Yang Heng , Qureshi Rehman , Sacan Ahmet
Published: June 2012

Background

Protein structures are better conserved than protein sequences, and consequently more functional information is available in structures than in sequences. However, proteins generally interact with other proteins and molecules via their surface regions and a backbone-only analysis of protein structures may miss many of the functional and evolutionary features. Surface information can help better elucidate proteins' functions and their interactions with other proteins. Computational analysis and comparison of protein surfaces is an important challenge to overcome to enable efficient and accurate functional characterization of proteins.

Methods

In this study we present a new method for representation and comparison of protein surface features. Our method is based on mapping the 3-D protein surfaces onto 2-D maps using various dimension reduction methods. We have proposed area and neighbor based metrics in order to evaluate the accuracy of this surface representation. In order to capture functionally relevant information, we encode geometric and biochemical features of the protein, such as hydrophobicity, electrostatic potential, and curvature, into separate color channels in the 2-D map. The resulting images can then be compared using efficient 2-D image registration methods to identify surface regions and features shared by proteins.

Results

We demonstrate the utility of our method and characterize its performance using both synthetic and real data. Among the dimension reduction methods investigated, SNE, LandmarkIsomap, Isomap, and Sammon's mapping provide the best performance in preserving the area and neighborhood properties of the original 3-D surface. The enriched 2-D representation is shown to be useful in characterizing the functional site of chymotrypsin and able to detect structural similarities in heat shock proteins. A texture mapping using the 2-D representation is also proposed as an interesting application to structure visualization.
High performance transcription factor-DNA docking with GPU computing
Authors: Wu Jiadong , Hong Bo , Takeda Takako , Guo Jun-tao
Published: June 2012

Background

Protein-DNA docking is a very challenging problem in structural bioinformatics and has important implications in a number of applications, such as structure-based prediction of transcription factor binding sites and rational drug design. Protein-DNA docking is very computational demanding due to the high cost of energy calculation and the statistical nature of conformational sampling algorithms. More importantly, experiments show that the docking quality depends on the coverage of the conformational sampling space. It is therefore desirable to accelerate the computation of the docking algorithm, not only to reduce computing time, but also to improve docking quality.

Methods

In an attempt to accelerate the sampling process and to improve the docking performance, we developed a graphics processing unit (GPU)-based protein-DNA docking algorithm. The algorithm employs a potential-based energy function to describe the binding affinity of a protein-DNA pair, and integrates Monte-Carlo simulation and a simulated annealing method to search through the conformational space. Algorithmic techniques were developed to improve the computation efficiency and scalability on GPU-based high performance computing systems.

Results

The effectiveness of our approach is tested on a non-redundant set of 75 TF-DNA complexes and a newly developed TF-DNA docking benchmark. We demonstrated that the GPU-based docking algorithm can significantly accelerate the simulation process and thereby improving the chance of finding near-native TF-DNA complex structures. This study also suggests that further improvement in protein-DNA docking research would require efforts from two integral aspects: improvement in computation efficiency and energy function design.

Conclusions

We present a high performance computing approach for improving the prediction accuracy of protein-DNA docking. The GPU-based docking algorithm accelerates the search of the conformational space and thus increases the chance of finding more near-native structures. To the best of our knowledge, this is the first ad hoc effort of applying GPU or GPU clusters to the protein-DNA docking problem.
Prediction of heme binding residues from protein sequences with integrative sequence profiles
Authors: Xiong Yi , Liu Juan , Zhang Wen , Zeng Tao
Published: June 2012

Background

The heme-protein interactions are essential for various biological processes such as electron transfer, catalysis, signal transduction and the control of gene expression. The knowledge of heme binding residues can provide crucial clues to understand these activities and aid in functional annotation, however, insufficient work has been done on the research of heme binding residues from protein sequence information.

Methods

We propose a sequence-based approach for accurate prediction of heme binding residues by a novel integrative sequence profile coupling position specific scoring matrices with heme specific physicochemical properties. In order to select the informative physicochemical properties, we design an intuitive feature selection scheme by combining a greedy strategy with correlation analysis.

Results

Our integrative sequence profile approach for prediction of heme binding residues outperforms the conventional methods using amino acid and evolutionary information on the 5-fold cross validation and the independent tests.

Conclusions

The novel feature of an integrative sequence profile achieves good performance using a reduced set of feature vector elements.
Continued twitching of the latissimus dorsi miniflap after breast conservation therapy: a case report
Authors: Huang Du-Ping , Ye Xiao-He , Xiang You-qun , Zhang Xiao-Hua
Published: June 2012

We report a case of continued twitching of the latissimus dorsi muscle following breast conservation therapy, along with immediate reconstruction with a latissimus dorsi miniflap, which continued despite several attempts at control including BTX-A percutaneous local injection, and was finally cured by delayed division of the thoracodorsal nerve via a small well-tolerated axillary incision.
Synovial sarcoma of the buttocks presenting with a non-healing wound and rapid progression after local resection: a case report
Authors: Zhang Hai-Yan , Feng Ye , Zhang Zhuo , Gao Ge , Zhao Ji-Sheng
Published: June 2012

Synovial sarcoma is a malignant mesenchymal neoplasm that is frequently misdiagnosed as a benign condition because of its small size, slow growth, and well-delineated appearance. Rapid spread and early death occur rarely. Here we report a case of synovial sarcoma of the buttocks presenting with a non-healing wound and rapid progression after local resection in a 23-year-old woman. She initially found a slightly painful subcutaneous mass in the left buttock and underwent local excision. Postoperatively, she developed a non-healing wound that did not respond to conventional antibiotic therapy and local wound care, and pitting edema of the lower extremities. A magnetic resonance imaging scan revealed a large heterogeneous, irregular mass in the buttocks with regional lymph node involvement. Histological and immunohistochemical analyses suggested the diagnosis of a poorly differentiated synovial sarcoma. Her condition deteriorated dramatically shortly thereafter; she developed systemic edema and died of respiratory failure. This case suggests that synovial sarcoma may be fatal within months of recognition if improperly managed and stresses the importance of adequate pre-surgical evaluation and postoperative pathological analysis in the management of a subcutaneous mass.
A mass conserved splitting method for the nonlinear Schrödinger equation
Authors: Hua Dong-Ying , Li Xiang-Gui , Zhu Jiang
Published: June 2012

A mass conserved time-splitting difference method is presented for the one-dimensional dipolar Bose-Einstein condensates (BECs) described by a nonlocal nonlinear Schrödinger equation with a convolution term. As a result of the singularity in the convolution term, it brings difficulties both in mathematical analysis and in numerical simulations. By properly using the difference scheme to deal with the convolution term, an imaginary time method is given to compute the ground states and then a time-splitting method is obtained for dynamics of dipolar BECs. This time-splitting numerical method is mass conserved everywhere, and it has second-order accuracy and is also unconditionally stable. Numerical results are given to verify the stability and energy conservation when there is no blow up.

Mathematics Subject Classification (2010) 65M06; 35Q41.
Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier
Authors: van Doorn Ruben , Lopes Pinheiro Melissa A , Kooij Gijs , Lakeman Kim , van het Hof Bert , van der Pol Susanne MA , Geerts Dirk , van Horssen Jack , van der Valk Paul , van der Kam Elizabeth , Ronken Eric , Reijerkerk Arie , de Vries Helga E
Published: June 2012

Background

The sphingosine 1-phosphate (S1P) receptor modulator FTY720P (Gilenya®) potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB) functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P5 largely contributes to the maintenance of brain endothelial barrier function.

Methods

We analyzed the expression of S1P5 in human post-mortem tissues using immunohistochemistry. The function of S1P5 at the BBB was assessed in cultured human brain endothelial cells (ECs) using agonists and lentivirus-mediated knockdown of S1P5. Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration.

Results

We show that activation of S1P5 on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P5 in brain ECs. Interestingly, functional studies with these cells revealed that S1P5 strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P5 maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB.

Conclusion

Our findings demonstrate that S1P5 in brain ECs contributes to optimal barrier formation and maintenance of immune quiescence of the barrier endothelium.
Molecular characteristics and chromatin texture features in acute promyelocytic leukemia
Authors: De Mello Mariana R. B. , Albuquerque Dulcineia M , Pereira-Cunha Fernanda Gonçalves , Albanez Krizzia B , Pagnano Katia B. B. , Costa Fernando F , Metze Konradin , Lorand-Metze Irene
Published: June 2012

Background

Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients.

Methods

In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient’s outcome.

Results

Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x109/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R245, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient’s survival.

Conclusion

in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.
Assessment of characteristics of patients with cholelithiasis from economically deprived rural Karachi, Pakistan
Authors: Naeem Muhammad , Rahimnajjad Nasir Ali , Rahimnajjad Muhammad Kazim , Khurshid Madiha , Ahmed Qazi Jalaluddin , Shahid Syed Mariam , Khawar Faiza , Najjar Molham Mustafa
Published: June 2012

Background

Gallstones have been regarded as one of the most expensive diseases in Gastroenterology, posing a great economic burden on developing nations. The majority of Pakistani people live in rural areas where healthcare facilities are not available or are very primitive. We aim to assess the characteristics among cholelithiasis patients from rural Karachi so that a prevention campaign can be launched in rural underprivileged settings to reduce the economic burden of this preventable disease.

Method

A total of 410 patients were included in the study after giving verbal consent as well as written consent. Variables such as age, weight, height, body mass index (BMI), blood pressure, waist circumference, number of children, monthly family income, number of siblings, and number of family members, were considered in this questionnaire. All data was analysed by SPSS ver. 16.0. Mean and standard deviation (SD) were calculated for continuous variables. Frequency and percentages were calculated for categorical variables.

Results

Nearly 85.4% of the participants were female. The mean ± S.D. for age was 43.8 ± 9.59. Nearly 61% of the patients were illiterate. All of our patients were from low socioeconomic status and their mean salary ± S.D. was 6915 ± 1992 PKR (1 US $ = 90.37PKR). 75% of them were smokers with mean consumption ± S.D. of 7.5 ± 10 cigarettes per day. Fibre in diet was not used by 83.65% of patients. 40.2% were living in combined families. 61% were living in purchased homes. A positive history of diabetes mellitus was given by 45.1%, family history of cholelithiasis by 61% and history of hypertension by 31.7% of subjects. Soft drink consumption was given by 45.1% of patients; while only 8.5% used snacked daily. Tea was consumed by 95.1% of the subjects. Daily physical activity for 30 minutes was reported by only 13.4% of participants.

Conclusion

In conclusion, rural dwellers from low socioeconomic strata are neglected patients and illiteracy further adds fuel to the fire by decreasing the contact with the health professionals. Assessment of the characteristics are very important because considering the great socio-economic burden, an intervention strategy in the form of mass media campaign as well as small group discussions in such rural areas can be formulated and applied to high risk populations to reduce the burden and complications of gallstone disease.
Trends in the use of rehabilitation services in the community by people with mental disabilities in Israel; the factors involved
Authors: Hornik-Lurie Tzipi , Zilber Nelly , Lerner Yaacov
Published: June 2012

Background

In 2001, the Rehabilitation of the Mentally Disabled Law was implemented, defining a basket of rehabilitation services to which people with mental disabilities are entitled.

Objectives

To describe change over time in the characteristics of applicants to rehabilitation committees, types of referral agencies, and the proportion of those referred who were admitted. To identify factors affecting implementation of decisions to admit people with mental disabilities into different rehabilitation services and predictors of the length of time they remain in the services.

Methods

The study population consisted of all applicants to rehabilitation committees during 2001-2008. Rehabilitation services included hostels, supported housing, and vocational services. Data were extracted from Ministry of Health rehabilitation and psychiatric hospitalization case registers. Findings were analyzed using descriptive statistics, Kaplan-Meier survival analyses, and Cox regressions.

Results

There was a trend over time for more patients with shorter or no psychiatric hospitalization histories to be referred to rehabilitation services. Moreover, there was an increase in the proportion of referrals from the community, although the majority of referrals still came from psychiatric hospitals. Less than half of those recommended for a rehabilitation program were admitted and remained in a rehabilitation facility for one year or more. One factor predicting participants' longer stays in rehabilitation services after hospitalization was the proximity of the committees' decisions to the hospitalization. Another factor was the patient receiving vocational services while in residential care.

Conclusion

Although over time the new law has resulted in a broader spectrum of people with mental disabilities receiving rehabilitation services, additional efforts are needed to enable them to remain in the system for a sufficient amount of time. Programs addressing specific needs should be developed accordingly.
Belief is only half the truth - or why screening for heterophilic antibody interference in certain assays makes double sense
Authors: Bjerner Johan , Bolstad Nils , Piehler Armin
Published: June 2012

Background

Interference in immunoassays may cause both false-negative and false-positive results. It may be detected using a number of affirmative tests such as reanalysis of certain samples using different assay platforms with known bias, after the addition of blocker antibodies, or assessment of linearity and parallelism following serial doubling dilutions. One should look for interference where it is likely and has high medical impact. Probabilistic Bayesian reasoning is a statistical tool to identify samples where interference is most likely. But when looking for interference where it is likely, do we find it where it has the largest population health consequences?

Methods

We used information theory to quantify the effect of assay interference by calculating the Shannon information content (using logarithms with base 2). We then obtained lower bounds of the population health consequences of a particular test and combined these expressions to get lower bounds of the population health consequences of interference.

Results and conclusion

We suggest that assays having a low frequency of true positives should be the primary target of retesting because: (i) assays with a low frequency of true positives exhibit a high likelihood of interference and (ii) the population health consequences of false-positive results are generally higher for assays with a low frequency of true positives. Finally, we give a worked example having a realistic frequency of interference and test costs. In some immunoassays (e.g., tumour markers), adding a blocker to all tests can be a more cost-efficient mean than retesting positive samples.