bluuebunny/crossref_metadata_2025_split huggingface dataset:
The significance of translation regulation in the stress response
Authors: Picard Flora , Loubière Pascal , Girbal Laurence , Cocaign-Bousquet Muriel 
Published: August 2013

Abstract

Background
The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation.

Results
A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation.
To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although mRNA stabilization and lower dilution by growth counterbalanced this effect.

Conclusions
We show that the contribution of translational regulation to the control of gene expression is significant in the stress response. Post-transcriptional regulation is complex and not systematically co-directional with transcription regulation. Post-transcriptional regulation is important to the understanding of gene expression control.
SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression
Authors: Wang Lu , Liu Zhaozhe , Ma Dongchu , Piao Ying , Guo Fang , Han Yaling , Xie Xiaodong 
Published: August 2013

Abstract

Background
The multiple tyrosine kinase inhibitors SU6668 have a promising therapeutic effect on the progression of hematological malignancies and some solid tumors. Here, we determined its effect on triple negative breast cancer (TNBC) cells and explored the potential molecular mechanism.

Methods
In this study, MDA-MB-231 cells were treated with SU6668 (15 μM, 30 μM) for 72 h and the change of proliferation was examined by MTT and tablet cloning. DNA ploidy was detected by flow cytometric analysis with PI staining. Double-label immunofluorescence method was used to detect the expression and distribution of MTDH proteins. VEGFR2, HIF-1α, MTDH, E-cadhrein, and SMA expressions were detected by Western bolt assay.

Results
This study showed that SU6668 inhibited the proliferation and induced polyploidization of MDA-MB-231 cells in a dose dependent form. SU6668 exposure increased the distribution of MTDH in cytoplasm and decreased its distribution in nuclei. After the treatment of SU6668, VEGFR2, HIF-1α, MTDH and SMA proteins were down-regulated, while E-cadhrein was up-regulated in MDA-MB-231 cells.

Conclusions
In conclusion, SU6668 exposure maybe induces polyploidization, inhibit EMT and influence the expression of MTDH, which suppresses the proliferation in TNBC cells. MTDH is a key signal protein in downstream of VEGF/HIF-1αpathway in MDA-MB-231 cells, which may be used as the potential target in the treatment of TNBC.
A comprehensive survey of polymorphisms conferring anti-malarial resistance in Plasmodium falciparum across Pakistan
Authors: Khattak Aamer A , Venkatesan Meera , Jacob Christopher G , Artimovich Elena M , Nadeem Muhammad F , Nighat Farida , Hombhanje Francis , Mita Toshihiro , Malik Salman A , Plowe Christopher V 
Published: August 2013

Abstract

Background
Few studies have been conducted in Pakistan to determine the efficacy of chloroquine and sulphadoxine-pyrimethamine (SP), which remain in use as treatment for Plasmodium vivax and in combination with artesunate to treat Plasmodium falciparum, respectively. In this study, samples from several sites across Pakistan were characterized to determine prevalence of molecular resistance markers in the P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (
pfdhps) genes and the origin of chloroquine-resistant P. falciparum parasites.

Methods
Microscopy-confirmed malaria parasite-positive blood samples from 801 patients across the country were collected in 2011. Of these, 171 infections were identified by polymerase chain reaction (PCR) as P. falciparum and analysed by pyrosequencing for mutations conferring chloroquine resistance (pfcrt codons 72–76), multidrug resistance (pfmdr1 N86Y, Y184F, S1034C, N1042D and D1246Y), pyrimethamine resistance (pfdhfr, C50R, N51I, C59R, S108N and I164L) and sulphadoxine resistance (pfdhps, S436A, A437G, K540E, A581G and A613T/S). pfmdr1 gene copy number variation was determined by real-time PCR, and microsatellites flanking the pfcrt locus were typed to determine the origin of the chloroquine-resistant haplotype.

Results
The pfcrt K76T mutation was found in all samples as part of the S72/V73/M74/N75/T76 (SVMNT) haplotype. Microsatellites flanking pfcrt showed high similarity to the signature found in India and Papua New Guinea. pfmdr1 N86Y was found in 20% of samples and all samples harboured a single copy of the pfmdr 1 gene. The pfdhfr double mutation C59R + S108N was present in 87% of samples while the pfdhfr triple mutant (N51I + C59R + S108N) was not detected. Pfdhps A437G was found in 60% of samples. Pure pfdhps K540E was rare, at 4%, but mixed genotype 540 K/E was found in 77% of samples. Similarly, pure pfdhps A581G was found in 4% of the isolates while mixed 581A/G was found in 39% of samples.

Conclusions
These results suggest an emerging problem with multidrug resistant P. falciparum in Pakistan. The chloroquine resistance genotype has reached complete fixation in the population, with a microsatellite pattern indicative of a selective sweep. Moreover, the prevalence of mutations in both pfdhfr and pfdhps, albeit without the presence of the pfdhfr triple mutant, indicates that continued monitoring is warranted to assess whether SP remains efficacious as a partner drug for artesunate for the treatment of P. falciparum.
The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways
Authors: Luo Dong-Hua , Chen Qiu-Yan , Liu Huai , Xu Li-Hua , Zhang Hui-Zhong , Zhang Lu , Tang Lin-Quan , Mo Hao-Yuan , Huang Pei-Yu , Guo Xiang , Mai Hai-Qiang 
Published: August 2013

Abstract

Background
Recent studies have indicated that the expression of endothelin A receptor (ETAR) and chemokine receptor 4 (CXCR4) could be used as an indicator of the metastatic potential of nasopharyngeal carcinoma (NPC). The aim of this study was to determine the prognostic value of ETAR and CXCR4 in NPC patients and to reveal the interplay of the endothelin-1 (ET-1)/ETAR and stromal-derived factor-1(SDF-1)/CXCR4 pathways in promoting NPC cell motility.

Methods
Survival analysis was used to analyze the prognostic value of ETAR and CXCR4 expression in 153 cases of NPC. Chemotaxis assays were used to evaluate alterations in the migration ability of non-metastatic 6-10B and metastatic 5-8F NPC cells. Real-time PCR, immunoblotting, and flow cytometric analyses were used to evaluate changes in the expression levels of CXCR4 mRNA and protein induced by ET-1.

Results
The expression levels of ETAR and CXCR4 were closely related to each other and both correlated with a poor prognosis. A multivariate analysis showed that the expression levels of both ETAR and CXCR4 were independent prognostic factors for overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The migration of 6-10B and 5-8F cells was elevated by ET-1 in combination with SDF-1α. The knockdown of ETAR protein expression by siRNA reduced CXCR4 protein expression in addition to ETAR protein expression, leading to a decrease in the metastatic potential of the 5-8F cells. ET-1 induced CXCR4 mRNA and protein expression in the 6-10B NPC cells in a time- and concentration-dependent fashion and was inhibited by an ETAR antagonist and PI3K/AKT/mTOR and MAPK/ERK1/2 pathway inhibitors.

Conclusions
ETAR and CXCR4 expression levels are potential prognostic biomarkers in NPC patients. ETAR activation partially promoted NPC cell migration via a mechanism that enhanced functional CXCR4 expression.
Evaluation of anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies in patients with juvenile idiopathic arthritis
Authors: Gilliam Brooke E , Chauhan Anil K , Moore Terry L 
Published: August 2013

Abstract

Background
To determine the prevalence and significance of anti-citrullinated vimentin and anti-citrullinated type II collagen antibodies and elucidate their role in the disease process of juvenile idiopathic arthritis (JIA).

Methods
Sera were obtained from 95 patients with various subtypes of JIA, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. Antibodies were measured in the sera against citrullinated and native type II collagen and vimentin (vim1-16 and vim 59-74) by enzyme-linked immunosorbent assay. Samples were compared to anti-cyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) isotypes, and our previously measured anti-citrullinated fibrinogen and α-enolase antibodies on the same patient population, in addition to erythrocyte sedimentation rate and C-reactive protein. The relationship between the anti-citrullinated antibody profile and disease activity and joint damage were also investigated.

Results
Twenty-three JIA patients (24%) demonstrated reactivity to anti-citrullinated type II collagen. Ten JIA patients (10.5%) demonstrated reactivity to anti-citrullinated vimentin 1–16 antibodies and 7 (7.4%) to anti-citrullinated vimentin 59–74 antibodies. One IgM RF-positive polyarticular patient was positive for all 5 of the citrullinated autoantibodies tested. Thirty-seven different subsets of patients were identified based on their anti-citrullinated autoantibody and RF isotype profile. No significant associations were noted with anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies with joint damage or disease activity. Anti-citrullinated vimentin 59–74 antibodies demonstrated the highest overall specificity at 89.7%, with anti-citrullinated vimentin 1–16 and anti-citrullinated type II collagen antibodies at 86.2%.

Conclusion
This study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with various subtypes of JIA. It also demonstrates the frequent occurrence of anti-citrullinated type II collagen and anti-citrullinated fibrinogen antibodies. The presence of autoantibodies to citrullinated antigens in JIA patients is highly diverse.
Systematic review of clinical practice guidelines in the diagnosis and management of thyroid nodules and cancer
Authors: Huang Tsai-Wei , Lai Jun-Hung , Wu Mei-Yi , Chen Shiah-Lian , Wu Chih-Hsiung , Tam Ka-Wai 
Published: August 2013

Abstract

Background
Given the uncertainties regarding thyroid nodule assessment and management, physicians require systematically and transparently developed recommendations. This systematic review assesses the quality and consistency of the recommendations of international clinical practice guidelines (CPGs) for the diagnosis and management of thyroid nodules and cancer to assist physicians in making appropriate recommendations.

Methods
The CPGs on the management of thyroid nodules and cancer published before June 2013 were retrieved. All the reviewed guidelines were in English. Four reviewers independently assessed the rigor of guideline development by using the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument, and their reported evidence was evaluated.

Results
Ten eligible guidelines were included: nine had been developed by professional organizations, and the remaining guideline was endorsed by an independent regional body. Three guidelines achieved a score of greater than 50% in all six AGREE-II domains. Guidelines scored highest on the measurement of ‘scope and purpose’ (≥61.1% for eight CPGs) and lowest on the measurement of ‘applicability’ (≤38.5% for five CPGs). The overall quality ranged from 3.0 to 6.25 on a seven-point scale on the AGREE-II tool. Most CPG recommendations on the management of thyroid cancer were relatively consistent. Guidelines varied regarding the indication of fine-needle aspiration for thyroid nodules, as well as in their suggestions for postoperative radioiodine ablation.

Conclusions
Our analysis showed that the current CPGs varied in methodological quality. More effort is needed to improve the quality of recommendations on the diagnosis and management of thyroid nodules and cancer.
Alcohol intake, wine consumption and the development of depression: the PREDIMED study
Authors: Gea Alfredo , Beunza Juan J , Estruch Ramón , Sánchez-Villegas Almudena , Salas-Salvadó Jordi , Buil-Cosiales Pilar , Gómez-Gracia Enrique , Covas María-Isabel , Corella Dolores , Fiol Miquel , Arós Fernando , Lapetra José , Lamuela-Raventós Rosa-María , Wärnberg Julia , Pintó Xavier , Serra-Majem Lluis , Martínez-González Miguel A ,   for the PREDIMED GROUP
Published: August 2013

Abstract

Background
Alcoholic beverages are widely consumed. Depression, the most prevalent mental disorder worldwide, has been related to alcohol intake. We aimed to prospectively assess the association between alcohol intake and incident depression using repeated measurements of alcohol intake.

Methods
We followed-up 5,505 high-risk men and women (55 to 80 y) of the PREDIMED Trial for up to seven years. Participants were initially free of depression or a history of depression, and did not have any history of alcohol-related problems. A 137-item validated food frequency questionnaire administered by a dietician was repeated annually to assess alcohol intake. Participants were classified as incident cases of depression when they reported a new clinical diagnosis of depression, and/or initiated the use of antidepressant drugs. Cox regression analyses were fitted over 23,655 person-years.

Results
Moderate alcohol intake within the range of 5 to 15 g/day was significantly associated with lower risk of incident depression (hazard ratio (HR) and 95% confidence interval (95% CI) = 0.72 (0.53 to 0.98) versus abstainers). Specifically, wine consumption in the range of two to seven drinks/week was significantly associated with lower rates of depression (HR (95% CI) = 0.68 (0.47 to 0.98)).

Conclusions
Moderate consumption of wine may reduce the incidence of depression, while heavy drinkers seem to be at higher risk.
GEMBASSY: an EMBOSS associated software package for comprehensive genome analyses
Authors: Itaya Hidetoshi , Oshita Kazuki , Arakawa Kazuharu , Tomita Masaru 
Published: August 2013

Abstract
The popular European Molecular Biology Open Software Suite (EMBOSS) currently contains over 400 tools used in various bioinformatics researches, equipped with sophisticated development frameworks for interoperability and tool discoverability as well as rich documentations and various user interfaces. In order to further strengthen EMBOSS in the fields of genomics, we here present a novel EMBOSS associated software (EMBASSY) package named GEMBASSY, which adds more than 50 analysis tools from the G-language Genome Analysis Environment and its Representational State Transfer (REST) and SOAP web services. GEMBASSY basically contains wrapper programs of G-language REST/SOAP web services to provide intuitive and easy access to various annotations within complete genome flatfiles, as well as tools for analyzing nucleic composition, calculating codon usage, and visualizing genomic information. For example, analysis methods such as for calculating distance between sequences by genomic signatures and for predicting gene expression levels from codon usage bias are effective in the interpretation of meta-genomic and meta-transcriptomic data. GEMBASSY tools can be used seamlessly with other EMBOSS tools and UNIX command line tools. The source code written in C is available from GitHub (https://github.com/celery-kotone/GEMBASSY/) and the distribution package is freely available from the GEMBASSY web site (http://www.g-language.org/gembassy/).
MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice
Authors: Honeyman Lisa , Bazett Mark , Tomko Tomasz G , Haston Christina K 
Published: August 2013

Abstract

Background
Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory cell infiltration and deposition of extracellular matrix in lung tissue. As mouse models of bleomycin-induced pulmonary fibrosis display many of the same phenotypes observed in patients with idiopathic pulmonary fibrosis, they have been used to study various aspects of the disease, including altered expression of microRNAs.

Results
In this work, microRNA expression profiling of the lungs from treated C57BL/6J mice, relative to that of untreated controls, was undertaken to determine which alterations in microRNAs could in part regulate the fibrosis phenotype induced by bleomycin delivered through mini-osmotic pumps. We identified 11 microRNAs, including miR-21 and miR-34a, to be significantly differentially expressed (P < 0.01) in lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. In situ hybridization of both miR-21 and miR-34a indicated that they were expressed in alveolar macrophages. Using a previously reported gene expression profile, we identified 195 genes to be both predicted targets of the 11 microRNAs and of altered expression in bleomycin-induced lung disease of C57BL/6J mice. Pathway analysis with these 195 genes indicated that altered microRNA expression may be associated with hepatocyte growth factor signaling, cholecystokinin/gastrin-mediated signaling, and insulin-like growth factor (IGF-1) signaling, among others, in fibrotic lung disease. The relevance of the IGF-1 pathway in this model was then demonstrated by showing lung tissue of bleomycin treated C57BL/6J mice had increased expression of Igf1 and that increased numbers of Igf-1 positive cells, predominantly in macrophages, were detected in the lungs.

Conclusions
We conclude that altered microRNA expression in macrophages is a feature which putatively influences the insulin-like growth factor signaling component of bleomycin-induced pulmonary fibrosis.
Mycelial mass production of fungi Duddingtonia flagrans and Monacrosporium thaumasium under different culture conditions
Authors: da Silva Manoel Eduardo , de Araújo Jackson Victor , Braga Fabio Ribeiro , Borges Luana Alcântara , Soares Filippe Elias F , dos Santos Lima Walter , Guimarães Marcos Pezzi 
Published: August 2013

Abstract

Background

Duddingtonia flagrans and Monacrosporium thaumasium are promising fungus species in veterinary biological control of gastrointestinal nematodes because of their production capacity of fungal structures (conidia and/or chlamydospores), growth efficiency in laboratory solid media and especially their predatory capacity. However, their large-scale production remains a challenge. This work aimed at evaluating the mycelial mass production of D. flagrans (AC001 and CG722) and M. thaumasium (NF34A) nematophagous fungi under different culture conditions.

Results
The results did not present significant differences (p > 0.05) in mycelia mass production between the isolates cultured under pH 4.0. Furthermore, after 168 hrs., the isolate CG722 presented a lower production of mycelial mass in medium CM (corn meal) (p < 0.05).

Conclusion
We therefore concluded the use of culture media SD (soy dextrose) and CG (corn grits) at pH values between 6.0 and 7.0 is suitable for high mycelial mass production of D. flagrans and M. thaumasium.
Understanding of latent tuberculosis, its treatment and treatment side effects in immigrant and refugee patients
Authors: Butcher Katie , Biggs Beverley-Ann , Leder Karin , Lemoh Chris , O’Brien Daniel , Marshall Caroline 
Published: August 2013

Abstract

Background
Isoniazid treatment of latent tuberculosis infection (LTBI) is commonly prescribed in refugees and immigrants. We aimed to assess understanding of information provided about LTBI, its treatment and potential side effects.

Methods
A questionnaire was administered in clinics at a tertiary hospital. Total Knowledge (TKS) and Total Side Effect Scores (TSES) were derived. Logistic regression analyses were employed to correlate socio-demographic factors with knowledge.

Results
Fifty-two participants were recruited, 20 at isoniazid commencement and 32 already on isoniazid. The average TKS were 5.04/9 and 6.23/9 respectively and were significantly associated with interpreter use. Approximately half did not know how tuberculosis was transmitted. The average TSES were 5.0/7 and 3.5/7 respectively, but were not influenced by socio-demographic factors.

Conclusions
There was suboptimal knowledge about LTBI. Improvements in health messages delivered via interpreters and additional methods of distributing information need to be developed for this patient population.
Erectile function after permanent 125I prostate brachytherapy for localized prostate cancer
Authors: Njomnang Soh Patrice , Delaunay Boris , Thoulouzan Matthieu , Jonca Frederic , Bachaud Jean Marc , Delannes Martine , Soulie Michel , Huyghe Eric 
Published: August 2013

Abstract

Background and purpose
To analyze erectile function in men treated by prostate brachytherapy (PB) for localized prostate cancer.

Material and methods
Of a series of 270 sexually active men treated by PB, 241 (89%), mean age 65 yr (range, 43–80 yr), participated in a study on erectile function that was evaluated using the International Index of Erectile Function 5-item (IIEF-5) questionnaire before implantation and by postal survey after a mean follow-up of 36 months (range, 6–70 months).

Results
After PB, 27 patients (11%) had no erectile dysfunction (ED), 36 (15%) had mild ED, 58 (24%) had mild to moderate ED, 24 (10%) had moderate ED, 53 (22%) had severe ED and 43 (18%) were not sexually active. In patients with a preimplant IIEF score >12 (cut-off for intercourse with penetration), 73% had a deterioration of erectile function by at least one class after PB. Risk factors for ED after PB were age, preimplant IIEF score and prostate volume. Median time to ED onset was 16 months and was shorter with androgen deprivation (p = 0.007), diabetes (p = 0.03) and age over 55 (p = 0.01).

Conclusions
Following PB, the majority of patients progressively develop or major ED after a free interval that may last several months.

Support
Ligue Nationale contre le Cancer, France