bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term macrolide treatment for chronic respiratory disease
Authors: Spagnolo Paolo , Fabbri Leonardo M. , Bush Andrew 
Published: November 2012

Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert anti-inflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials.
Identification of novel genes involved in DNA damage response by screening a genome-wide Schizosaccharomyces pombe deletion library
Authors: Pan Xian , Lei Bingkun , Zhou Nan , Feng Biwei , Yao Wei , Zhao Xin , Yu Yao , Lu Hong 
Published: November 2012

Abstract

Background
DNA damage response (DDR) plays pivotal roles in maintaining genome integrity and stability. An effective DDR requires the involvement of hundreds of genes that compose a complicated network. Because DDR is highly conserved in evolution, studies in lower eukaryotes can provide valuable information to elucidate the mechanism in higher organisms. Fission yeast (Schizosaccharomyces pombe) has emerged as an excellent model for DDR research in recent years. To identify novel genes involved in DDR, we screened a genome-wide S. pombe haploid deletion library against six different DNA damage reagents. The library covered 90.5% of the nonessential genes of S. pombe.

Results
We have identified 52 genes that were actively involved in DDR. Among the 52 genes, 20 genes were linked to DDR for the first time. Flow cytometry analysis of the repair defective mutants revealed that most of them exhibited a defect in cell cycle progression, and some caused genome instability. Microarray analysis and genetic complementation assays were carried out to characterize 6 of the novel DDR genes in more detail. Data suggested that SPBC2A9.02 and SPAC27D7.08c were required for efficient DNA replication initiation because they interacted genetically with DNA replication initiation proteins Abp1 and Abp2. In addition, deletion of sgf73
+, meu29
+, sec65
+ or pab1
+ caused improper cytokinesis and DNA re-replication, which contributed to the diploidization in the mutants.

Conclusions
A genome-wide screen of genes involved in DDR emphasized the key role of cell cycle control in the DDR network. Characterization of novel genes identified in the screen helps to elucidate the mechanism of the DDR network and provides valuable clues for understanding genome stability in higher eukaryotes.
Next generation sequencing and de novo transcriptome analysis of Costus pictus D. Don, a non-model plant with potent anti-diabetic properties
Authors: Annadurai Ramasamy S , Jayakumar Vasanthan , Mugasimangalam Raja C , Katta Mohan AVSK , Anand Sanchita , Gopinathan Sreeja , Sarma Santosh Prasad , Fernandes Sunjay Jude , Mullapudi Nandita , Murugesan S , Rao Sudha Narayana 
Published: November 2012

AbstractBackgroundPhyto-remedies for diabetic control are popular among patients with Type II Diabetes mellitus (DM), in addition to other diabetic control measures. A number of plant species are known to possess diabetic control properties.Costus pictusD. Don is popularly known as “Insulin Plant” in Southern India whose leaves have been reported to increase insulin pools in blood plasma. Next Generation Sequencing is employed as a powerful tool for identifying molecular signatures in the transcriptome related to physiological functions of plant tissues. We sequenced the leaf transcriptome ofC. pictususing Illumina reversible dye terminator sequencing technology and used combination of bioinformatics tools for identifying transcripts related to anti-diabetic properties ofC. pictus.ResultsA total of 55,006 transcripts were identified, of which 69.15% transcripts could be annotated. We identified transcripts related to pathways of bixin biosynthesis and geraniol and geranial biosynthesis as major transcripts from the class of isoprenoid secondary metabolites and validated the presence of putative norbixin methyltransferase, a precursor of Bixin. The transcripts encoding these terpenoids are known to be Peroxisome Proliferator-Activated Receptor (PPAR) agonists and anti-glycation agents. Sequential extraction and High Performance Liquid Chromatography (HPLC) confirmed the presence of bixin inC. pictusmethanolic extracts. Another significant transcript identified in relation to anti-diabetic, anti-obesity and immuno-modulation is of Abscisic Acid biosynthetic pathway. We also report many other transcripts for the biosynthesis of antitumor, anti-oxidant and antimicrobial metabolites ofC. pictusleaves.ConclusionSolid molecular signatures (transcripts related to bixin, abscisic acid, and geranial and geraniol biosynthesis) for the anti-diabetic properties ofC. pictusleaves and vital clues related to the other phytochemical functions like antitumor, anti-oxidant, immuno-modulatory, anti-microbial and anti-malarial properties through the secondary metabolite pathway annotations are reported. The data provided will be of immense help to researchers working in the treatment of DM using herbal therapies.
An S/T-Q cluster domain census unveils new putative targets under Tel1/Mec1 control
Authors: Cheung Hannah C , San Lucas F Anthony , Hicks Stephanie , Chang Kyle , Bertuch Alison A , Ribes-Zamora Albert 
Published: November 2012

Abstract

Background
The cellular response to DNA damage is immediate and highly coordinated in order to maintain genome integrity and proper cell division. During the DNA damage response (DDR), the sensor kinases Tel1 and Mec1 in Saccharomyces cerevisiae and ATM and ATR in human, phosphorylate multiple mediators which activate effector proteins to initiate cell cycle checkpoints and DNA repair. A subset of kinase substrates are recognized by the S/T-Q cluster domain (SCD), which contains motifs of serine (S) or threonine (T) followed by a glutamine (Q). However, the full repertoire of proteins and pathways controlled by Tel1 and Mec1 is unknown.

Results
To identify all putative SCD-containing proteins, we analyzed the distribution of S/T-Q motifs within verified Tel1/Mec1 targets and arrived at a unifying SCD definition of at least 3 S/T-Q within a stretch of 50 residues. This new SCD definition was used in a custom bioinformatics pipeline to generate a census of SCD-containing proteins in both yeast and human. In yeast, 436 proteins were identified, a significantly larger number of hits than were expected by chance. These SCD-containing proteins did not distribute equally across GO-ontology terms, but were significantly enriched for those involved in processes related to the DDR. We also found a significant enrichment of proteins involved in telophase and cytokinesis, protein transport and endocytosis suggesting possible novel Tel1/Mec1 targets in these pathways. In the human proteome, a wide range of similar proteins were identified, including homologs of some SCD-containing proteins found in yeast. This list also included high concentrations of proteins in the Mediator, spindle pole body/centrosome and actin cytoskeleton complexes.

Conclusions
Using a bioinformatic approach, we have generated a census of SCD-containing proteins that are involved not only in known DDR pathways but several other pathways under Tel1/Mec1 control suggesting new putative targets for these kinases.
Assessment of virulence diversity of methicillin-resistant Staphylococcus aureus strains with a Drosophila melanogaster infection model
Authors: Wu Kaiyu , Conly John , Surette Michael , Sibley Christopher , Elsayed Sameer , Zhang Kunyan 
Published: November 2012

Abstract

Background

Staphylococcus aureus strains with distinct genetic backgrounds have shown different virulence in animal models as well as associations with different clinical outcomes, such as causing infection in the hospital or the community. With S. aureus strains carrying diverse genetic backgrounds that have been demonstrated by gene typing and genomic sequences, it is difficult to compare these strains using mammalian models. Invertebrate host models provide a useful alternative approach for studying bacterial pathogenesis in mammals since they have conserved innate immune systems of biological defense. Here, we employed Drosophila melanogaster as a host model for studying the virulence of S. aureus strains.

Results
Community-associated methicillin-resistant S. aureus (CA-MRSA) strains USA300, USA400 and CMRSA2 were more virulent than a hospital-associated (HA)-MRSA strain (CMRSA6) and a colonization strain (M92) in the D. melanogaster model. These results correlate with bacterial virulence in the Caenorhabditis elegans host model as well as human clinical data. Moreover, MRSA killing activities in the D. melanogaster model are associated with bacterial replication within the flies. Different MRSA strains induced similar host responses in D. melanogaster, but demonstrated differential expression of common bacterial virulence factors, which may account for the different killing activities in the model. In addition, hemolysin α, an important virulence factor produced by S. aureus in human infections is postulated to play a role in the fly killing.

Conclusions
Our results demonstrate that the D. melanogaster model is potentially useful for studying S. aureus pathogenicity. Different MRSA strains demonstrated diverse virulence in the D. melanogaster model, which may be the result of differing expression of bacterial virulence factors in vivo.
Highly specific fiber optic immunosensor coupled with immunomagnetic separation for detection of low levels of Listeria monocytogenes and L. ivanovii
Authors: Mendonça Marcelo , Conrad Neida L , Conceição Fabricio R , Moreira Ângela N , da Silva Wladimir P , Aleixo José AG , Bhunia Arun K 
Published: November 2012

Abstract

Background
Immunomagnetic separation (IMS) and immunoassays are widely used for pathogen detection. However, novel technology platforms with highly selective antibodies are essential to improve detection sensitivity, specificity and performance. In this study, monoclonal antibodies (MAbs) against Internalin A (InlA) and p30 were generated and used on paramagnetic beads of varying diameters for concentration, as well as on fiber-optic sensor for detection.

Results
Anti-InlA MAb-2D12 (IgG2a subclass) was specific for Listeria monocytogenes and L. ivanovii, and p30-specific MAb-3F8 (IgM) was specific for the genus Listeria. At all bacterial concentrations (103–108 CFU/mL) tested in the IMS assay; the 1-μm diameter MyOne beads had significantly higher capture efficiency (P < 0.05) than the 2.8-μm diameter M-280 beads with both antibodies. The highest capture efficiency for MyOne-2D12 (49.2% for 105 CFU/mL) was significantly higher (P < 0.05) than that of MyOne-3F8 (16.6 %) and Dynabeads anti-Listeria antibody (9 %). Furthermore, capture efficiency for MyOne-2D12 was highly specific for L. monocytogenes and L. ivanovii. Subsequently, we captured L. monocytogenes by MyOne-2D12 and MyOne-3F8 from hotdogs inoculated with mono- or co-cultures of L. monocytogenes and L. innocua (10–40 CFU/g), enriched for 18 h and detected by fiber-optic sensor and confirmed by plating, light-scattering, and qPCR assays. The detection limit for L. monocytogenes and L. ivanovii by the fiber-optic immunosensor was 3 × 102 CFU/mL using MAb-2D12 as capture and reporter antibody. Selective media plating, light-scattering, and qPCR assays confirmed the IMS and fiber-optic results.

Conclusions
IMS coupled with a fiber-optic sensor using anti-InlA MAb is highly specific for L. monocytogenes and L. ivanovii and enabled detection of these pathogens at low levels from buffer or food.
MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma
Authors: Cui Li , Zhou Hua , Zhao Hu , Zhou Yaojun , Xu Renfang , Xu Xianlin , Zheng Lu , Xue Zhong , Xia Wei , Zhang Bo , Ding Tao , Cao Yunjie , Tian Zinong , Shi Qianqian , He Xiaozhou 
Published: November 2012

Abstract

Background
A growing body of evidence suggests that microRNAs (miRNAs) play an important role in cancer diagnosis and therapy. MicroRNA-99a (miR-99a), a potential tumor suppressor, is downregulated in several human malignancies. The expression and function of miR-99a, however, have not been investigated in human renal cell carcinoma (RCC) so far. We therefore examined the expression of miR-99a in RCC cell lines and tissues, and assessed the impact of miR-99a on the tumorigenesis of RCC.

Methods
MiR-99a levels in 40 pairs of RCC and matched adjacent non-tumor tissues were assessed by real-time quantitative Reverse Transcription PCR (qRT-PCR). The RCC cell lines 786-O and OS-RC-2 were transfected with miR-99a mimics to restore the expression of miR-99a. The effects of miR-99a were then assessed by cell proliferation, cell cycle, transwell, and colony formation assay. A murine xenograft model of RCC was used to confirm the effect of miR-99a on tumorigenicity in vivo. Potential target genes were identified by western blotting and luciferase reporter assay.

Results
We found that miR-99a was remarkably downregulated in RCC and low expression level of miR-99a was correlated with poor survival of RCC patients. Restoration of miR-99a dramatically suppressed RCC cells growth, clonability, migration and invasion as well as induced G1-phase cell cycle arrest in vitro. Moreover, intratumoral delivery of miR-99a could inhibit tumor growth in murine xenograft models of human RCC. In addition, we also fond that mammalian target of rapamycin (mTOR) was a direct target of miR-99a in RCC cells. Furthermore, siRNA-mediated knockdown of mTOR partially phenocopied the effect of miR-99a overexpression, suggesting that the tumor suppressive role of miR-99a may be mediated primarily through mTOR regulation.

Conclusions
Collectively, these results demonstrate for the first time, to our knowledge, that deregulation of miR-99a is involved in the etiology of RCC partially via direct targeting mTOR pathway, which suggests that miR-99a may offer an attractive new target for diagnostic and therapeutic intervention in RCC.
Screening of Finnish RAD51Cfounder mutations in prostate and colorectal cancer patients
Authors: Pelttari Liisa M , Nurminen Riikka , Gylfe Alexandra , Aaltonen Lauri A , Schleutker Johanna , Nevanlinna Heli 
Published: November 2012

Abstract

Background
Rare, heterozygous germline mutations in the RAD51C gene have been found in breast and ovarian cancer families. In the Finnish population, we have identified two founder mutations in RAD51C that increase the risk of ovarian cancer but not breast cancer in the absence of ovarian cancer. Risk for other cancers has not been studied.

Methods
To study the role of RAD51C mutations in other common cancer types, we genotyped the Finnish RAD51C founder mutations c.837 + 1G > A and c.93delG in 1083 prostate cancer patients and 802 colorectal cancer patients using TaqMan Real-Time PCR.

Results
No RAD51C mutations c.837 + 1G > A or c.93delG were detected among the prostate or colorectal cancer patients.

Conclusions
The results suggest that the RAD51C mutations do not predispose to prostate or colorectal cancer.
The LIFE child study: a life course approach to disease and health
Authors: Quante Mirja , Hesse Mara , Döhnert Mirko , Fuchs Michael , Hirsch Christian , Sergeyev Elena , Casprzig Nora , Geserick Mandy , Naumann Stephanie , Koch Christiane , Sabin Matthew A , Hiemisch Andreas , Körner Antje , Kiess Wieland ,   for the LIFE Child Study Investigators
Published: November 2012

Abstract

Background
Profound knowledge about child growth, development, health, and disease in contemporary children and adolescents is still rare. Epidemiological studies together with new powerful research technologies present exciting opportunities to the elucidation of risk factor-outcome associations with potentially major consequences for prevention, diagnosis and treatment.

Aim
To conduct a unique prospective longitudinal cohort study in order to assess how environmental, metabolic and genetic factors affect growth, development and health from fetal life to adulthood.

Methods
The ‘Leipzig Research Centre for Civilization Diseases (LIFE) Child Study’ focuses on two main research objectives: (1) monitoring of normal growth, development and health; (2) non-communicable diseases such as childhood obesity and its co-morbidities, atopy and mental health problems. Detailed assessments will be conducted alongside long-term storage of biological samples in 2,000 pregnant women and more than 10,000 children and their families.

Results
Close coordination and engagement of a multidisciplinary team in the LIFE Child study successfully established procedures and systems for balancing many competing study and ethical needs. Full participant recruitment and complete data collection started in July 2011. Early data indicate a high acceptance rate of the study program, successful recruitment strategies and the establishment of a representative cohort for the population of Leipzig. A series of subprojects are ongoing, and analyses and publications are on their way.

Discussion
This paper addresses key elements in the design and implementation of the new prospective longitudinal cohort study LIFE Child. Given the recognized need for long-term data on adverse effects on health and protective factors, our study data collection should provide magnificent opportunities to examine complex interactions that govern the emergence of non-communicable diseases.
Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats
Authors: Chen Wei-Cheng , Liou Shorong-Shii , Tzeng Thing-Fong , Lee Shiow-Ling , Liu I-Min 
Published: November 2012

Abstract

Background

Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE) was investigated for its healing efficiency in a rat excision wound model.

Methods
Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing.

Results
LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production.

Conclusions
The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair.
The effects of Sutaehwan-Gami on menopausal symptoms induced by ovariectomy in rats
Authors: Kim Dong-Il , Choi Min Sun , Pak Sok Cheon , Lee Seung-bok , Jeon Songhee 
Published: November 2012

Abstract

Background
This study was undertaken to evaluate the beneficial effects of a modified prescription of Sutaehwan named Sutaehwan-Gami (SG), created by adding Rhizoma dioscoreae and Carthami semen to Sutaehwan, on menopausal symptoms.

Methods
To evaluate the estrogenic effect of SG, we first examined estrogen receptor (ER) activation by SG treatment in breast adenocarcinoma cells and confirmed the estrogenic effect of SG in vivo ovariectomized rats. The animals were randomized into four groups: Sham operated group (Sham), saline treated ovariectomized group (OVX), SG treated group (SG) and raloxifene treated group (RLX). Animals were provided with SG at a dose of 500 mg/kg bw/day and RLX at a dose of 5.4 mg/kg bw/day with standard rat pellets for 3 months.

Results
SG significantly increased ERα phosphorylation, and its downstream effectors, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation in breast adenocarcinoma cells. Treatment with SG reversed ovariectomy-induced uterine weight reduction and weight gain. Decreases in the levels of GOT and GPT were observed in the SG group. The significantly reduced E2β level in OVX rats was raised by treatment with SG. Moreover, SG significantly increased the phosphorylation levels of ERK and Akt in the uterus.

Conclusion
Taken together, these data indicate that SG has phytoestrogen-like properties through ERK and Akt activation, implying that it could be protective and beneficial for the management of menopausal symptoms.
An antibody microarray analysis of serum cytokines in neurodegenerative Parkinsonian syndromes
Authors: Mahlknecht Philipp , Stemberger Sylvia , Sprenger Fabienne , Rainer Johannes , Hametner Eva , Kirchmair Rudolf , Grabmer Christoph , Scherfler Christoph , Wenning Gregor K , Seppi Klaus , Poewe Werner , Reindl Markus 
Published: November 2012

Abstract

Background
Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum antibody microarray to screen for differentially regulated cytokines in Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

Results
Serum samples were obtained from patients with clinical diagnoses of PD (n = 117), MSA (n = 31) and PSP/CBS (n = 38) and 99 controls. Cytokine profiles of sera from patients and controls were analyzed with a semiquantitative human antibody array for 174 cytokines and the expression of 12 cytokines was found to be significantly altered. In a next step, results from the microarray experiment were individually validated by different immunoassays. Immunoassay validation confirmed a significant increase of median PDGF-BB levels in patients with PSP/CBS, MSA and PD and a decrease of median prolactin levels in PD. However, neither PDGF-BB nor prolactin were specific biomarkers to discriminate PSP/CBS, MSA, PD and controls.

Conclusions
In our unbiased cytokine array based screening approach and validation by a different immunoassay only two of 174 cytokines were significantly altered between patients and controls.