Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Pathological femoral neck fracture caused by an echinococcus cyst of the vastus lateralis - case report

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal hydatid cysts are rare, but being locally invasive, can potentially cause significant deformity or pathological fracture.</p> <p>Case presentation</p> <p>A 39 y.o. male presented to our orthopaedic outpatient clinic complaining of severe right hip pain, and inability to ambulate. Symptoms were not preceded by trauma. Subsequent imaging confirmed a large, 17 × 3 × 5 cm echinococcus cyst in the vastus lateralis, causing erosion of the proximal metaphysis of the femur. As a consequence the patient suffered a non-traumatic pathological intertrochanteric femur fracture. The patient was treated with an en-bloc excision of the lesion - the affected soft tissue envelope containing the large cyst - and as a second surgical step a cemented total hip replacement (THR) was implanted under the same anaesthetic.</p> <p>The manuscript reviews the literature regarding musculoskeletal hydatid disease.</p

E pluribus plurima: Multidimensional indices and clinical phenotypes in COPD

as the picture of COPD becomes more complex and the results from large studies generate the need of further research, it is clear the close link between the definition of clinical phenotypes and the validation of either single or multidimensional indices

Histological response to injected gluteraldehyde cross-linked bovine collagen based implant in a rat model

BACKGROUND: The aim of present study is to investigate the short and long term histopathological alterations caused by submucosal injection of gluteraldehyde cross-linked bovine collagen based on an experimental rat model. METHODS: Sixty Sprague-Dawley rats were assigned into two groups as group I and II each containing 30 rats. 0.1 ml of saline solution and 0.1 ml of gluteraldehyde cross-linked bovine collagen were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into 3 other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrification period. Group IA and IIA, IB and IIB, IC and IIC rats (10 rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary ingrowth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at ×10 magnification. The results were assessed using t-tests for paired and independent samples, with p < 0.05 considered to indicate significant differences; all values were presented as the mean (SD). RESULTS: Migration to the brain was not detected in any group. Significant histopathological changes in the gluteraldehyde cross-linked bovine collagen injected groups were fibroblast invasion in 93.3%, collagen formation in 73.3%, capillary ingrowth in 46.6%, inflamatory reaction in 20%. CONCLUSION: We emphasize that the usage of gluteraldehyde cross-linked bovine collagen in children appears to be safe for endoscopic treatment of vesicoureteral reflux

A multi-disciplinary perspective on emergent and future innovations in peer review [version 1; peer review: 2 approved with reservations]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of Web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform current models while avoiding as many of the biases of existing systems as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that, at least partially, resolves many of the technical and social issues associated with peer review, and can potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

miR-17* Suppresses Tumorigenicity of Prostate Cancer by Inhibiting Mitochondrial Antioxidant Enzymes

Aberrant micro RNA (miRNA) expression has been implicated in the pathogenesis of cancer. Recent studies have shown that the miR-17-92 cluster is overexpressed in many types of cancer. The oncogenic function of mature miRNAs encoded by the miR-17–92 cluster has been identified from the 5′ arm of six precursors. However, the function of the miRNAs produced from the 3′ arm of these precursors remains unknown. The present study demonstrates that miR-17* is able to suppress critical primary mitochondrial antioxidant enzymes, such as manganese superoxide dismutase (MnSOD), glutathione peroxidase-2 (GPX2) and thioredoxin reductase-2 (TrxR2). Transfection of miR-17* into prostate cancer PC-3 cells significantly reduces levels of the three antioxidant proteins and activity of the luciferase reporter under the control of miR-17* binding sequences located in the 3′-untranslated regions of the three target genes. Disulfiram (DSF), a dithiolcarbomate drug shown to have an anticancer effect, induces the level of mature miR-17* and cell death in PCa cells, which can be attenuated by transfection of antisense miR-17*. Increasing miR-17* level in PC-3 cells by a Tet-on based conditional expression system markedly suppresses its tumorigencity. These results suggest that miR-17* may suppress tumorigenicity of prostate cancer through inhibition of mitochondrial antioxidant enzymes

Antibodies elicited in adults by a primary Plasmodium falciparum blood-stage infection recognize different epitopes compared with immune individuals

<p>Abstract</p> <p>Background</p> <p>Asexual stage antibody responses following initial <it>Plasmodium falciparum </it>infections in previously healthy adults may inform vaccine development, yet these have not been as intensively studied as they have in populations from malaria-endemic areas.</p> <p>Methods</p> <p>Serum samples were collected over a six-month period from twenty travellers having returned with falciparum malaria. Fourteen of these were malaria-naïve and six had a past history of one to two episodes of malaria. Antibodies to seven asexual stage <it>P. falciparum </it>antigens were measured by ELISA. Invasion inhibitory antibody responses to the 19kDa fragment of merozoite surface protein 1 (MSP1₁₉) were determined.</p> <p>Results</p> <p>Short-lived antibody responses were found in the majority of the subjects. While MSP1₁₉antibodies were most common, MSP1 block 2 antibodies were significantly less frequent and recognized conserved domains. Antibodies to MSP2 cross-reacted to the dimorphic allelic families and anti-MSP2 isotypes were not IgG3 skewed as shown previously. MSP1₁₉invasion inhibiting antibodies were present in 9/20 patients. A past history of malaria did not influence the frequency of these short-lived, functional antibodies (p = 0.2, 2-tailed Fisher's exact test).</p> <p>Conclusion</p> <p>Adults infected with <it>P. falciparum </it>for the first time, develop relatively short-lived immune responses that, in the case of MSP1₁₉, are functional. Antibodies to the polymorphic antigens studied were particularly directed to allelic family specific, non-repetitive and conserved determinants and were not IgG subclass skewed. These responses are substantially different to those found in malaria immune individuals.</p

Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

Background: Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s) by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods: The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc) and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M(2) and M(3) receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE), TNF-alpha, PDGF-AB or IL-1 beta. Results: Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-alpha or PDGF-AB, but not with IL-1 beta. Pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of I kappa B-kinase-2 (SC514) and MEK1/2 (U0126), both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of I kappa B alpha and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1b in hASMc. Conclusions: We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of I kappa B alpha and ERK1/2. This mechanism could be of importance for COPD patients usin

MiR-107 and MiR-185 Can Induce Cell Cycle Arrest in Human Non Small Cell Lung Cancer Cell Lines

BACKGROUND: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors