A Novel Algorithm for Detecting Protein Complexes with the Breadth First Search

Most biological processes are carried out by protein complexes. A substantial number of false positives of the protein-protein interaction (PPI) data can compromise the utility of the datasets for complexes reconstruction. In order to reduce the impact of such discrepancies, a number of data integration and affinity scoring schemes have been devised. The methods encode the reliabilities (confidence) of physical interactions between pairs of proteins. The challenge now is to identify novel and meaningful protein complexes fromthe weighted PPI network. To address this problem, a novel protein complex mining algorithm ClusterBFS (Cluster with Breadth-First Search) is proposed. Based on the weighted density, ClusterBFS detects protein complexes of the weighted network by the breadth first search algorithm, which originates from a given seed protein used as starting-point. The experimental results show that ClusterBFS performs significantly better than the other computational approaches in terms of the identification of protein complexes

A comparison of the functional modules identified from time course and static PPI network data

<p>Abstract</p> <p>Background</p> <p>Cellular systems are highly dynamic and responsive to cues from the environment. Cellular function and response patterns to external stimuli are regulated by biological networks. A protein-protein interaction (PPI) network with static connectivity is dynamic in the sense that the nodes implement so-called functional activities that evolve in time. The shift from static to dynamic network analysis is essential for further understanding of molecular systems.</p> <p>Results</p> <p>In this paper, Time Course Protein Interaction Networks (TC-PINs) are reconstructed by incorporating time series gene expression into PPI networks. Then, a clustering algorithm is used to create functional modules from three kinds of networks: the TC-PINs, a static PPI network and a pseudorandom network. For the functional modules from the TC-PINs, repetitive modules and modules contained within bigger modules are removed. Finally, matching and GO enrichment analyses are performed to compare the functional modules detected from those networks.</p> <p>Conclusions</p> <p>The comparative analyses show that the functional modules from the TC-PINs have much more significant biological meaning than those from static PPI networks. Moreover, it implies that many studies on static PPI networks can be done on the TC-PINs and accordingly, the experimental results are much more satisfactory. The 36 PPI networks corresponding to 36 time points, identified as part of this study, and other materials are available at <url>http://bioinfo.csu.edu.cn/txw/TC-PINs.</url></p

Retropharyngeal Lymph Node Metastasis Diagnosed by Magnetic Resonance Imaging in Hypopharyngeal Carcinoma: A Retrospective Analysis From Chinese Multi-Center Data

BackgroundTo assess the prevalence, risk factors and prognostic significance of retropharyngeal lymph node (RPLN) metastasis diagnosed by magnetic resonance imaging (MRI) in patients with hypopharyngeal squamous cell carcinoma (HPSCC).Methods259 patients from three cancer institutions in China from Jan 2010 to Dec 2018 were analyzed, retrospectively. All the patients had been given pre-treatment magnetic resonance imaging (MRI) of head and neck and were then treated with definitive radiotherapy with or without chemotherapy. Pretreatment diagnostic MRIs were reviewed by a dedicated head and neck radiologist, for the presence or absence of radiographically positive RPLN, cervical LN and tumor invasion.Demographic variables were analysed by descriptive statistics using SPSS 20.0. Predictors of the presence of RPLN and its prognostic significance were examined.ResultsRPLN metastasis was discovered in 44 patients (17%). Logistic analysis showed that posterior pharyngeal wall (PPW) primary tumor; PPW invasion; N2-3; multiple cervical lymph node (LN) involvement (&gt;2 LNs) were associated with RPLN metastasis, with metastasis rates 37%, 30%, 31% and 33% respectively. Patients with RPLN metastasis had a significantly reduced 5-year overall survival (OS) and disease-free survival (DFS) compared to the non-RPLN metastasis group (OS 28% vs. 48%, p=0.001; DFS 25% vs. 41%, p=0.040).ConclusionsRPLN metastasis was not uncommon in HPSCC patients. Risk factors were: PPW primary tumor, PPW invasion and cervical LN status. RPLN metastasis is a poor prognosticator for survival

Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue

Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a new brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown adipocytes into high-thermogenic cells. A thermoneutral environment had the opposite effect. The recruitment of high-thermogenic brown adipocytes by cold stimulation is not affected by high fat diet feeding, but it does substantially decline with age. Our results revealed a high degree of functional heterogeneity of brown adipocytes

Rapamycin-loaded nanoparticles for inhibition of neointimal hyperplasia in experimental vein grafts

<p>Abstract</p> <p>Background</p> <p>Nanoparticles possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded nanoparticles(NPs) can reduce neointima formation in a rat model of vein graft disease.</p> <p>Methods</p> <p>Poly(lactic-co-glycolic acid) (PLGA) NPs containing rapamycin was prepared using an oil/water solvent evaporation technique. Nanoparticle size and morphology were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA (RPLGA) NPs was studied using MTT Assay. Excised rat jugular vein was treated ex vivo with blank-NPs, or rapamycin-loaded NPs, then interposed back into the carotid artery position using a cuff technique. Grafts were harvested at 21 days and underwent morphometric analysis as well as immunohistochemical analysis.</p> <p>Results</p> <p>Rapamycin was efficiently loaded in PLGA nanoparticles with an encapsulation efficiency was 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/ml significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts shown that the concentration of rapamycin in vein grafts at 3 weeks after grafting were 0.9 ± 0.1 μg/g. In grafted veins without treatment intima-media thickness was 300.4 ±181.5 μm after grafting 21 days. Whereas, Veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 μm (p = 0.001). CD-31 staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization in 21 days vein grafts with no significant effect of blank or rapamycin-loaded NPs group.</p> <p>Conclusions</p> <p>We conclude that sustained-release rapamycin from rapymycin loaded NPs inhibits vein graft thickening without affecting the reendothelialization in rat carotid vein-to-artery interposition grafts and this may be a promising therapy for the treatment of vein graft disease.</p

Presence of qnr gene in Escherichia coli and Klebsiella pneumoniae resistant to ciprofloxacin isolated from pediatric patients in China

<p>Abstract</p> <p>Background</p> <p>Quinolone resistance in <it>Enterobacteriaceae </it>results mainly from mutations in type II DNA topoisomerase genes and/or changes in the expression of outer membrane and efflux pumps. Several recent studies have indicated that plasmid-mediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. In China, the presence of the <it>qnr </it>gene in the clinical isolates of <it>Enterobacteriaceae </it>has been reported, but this transmissible quinolone resistance gene has not been detected in strains isolated singly from pediatric patients. Because quinolones associated with a variety of adverse side effects on children, they are not authorized for pediatric use. This study therefore aimed to investigate the presence of the <it>qnr </it>gene in clinical isolates of <it>E. coli </it>and <it>K. pneumoniae </it>from pediatric patients in China.</p> <p>Methods</p> <p>A total 213 of non-repetitive clinical isolates resistant to ciprofloxacin from <it>E. coli </it>and <it>K. pneumoniae </it>were collected from hospitalized patients at five children's hospital in Beijing, Shanghai, Guangzhou, and Chongqing. The isolates were screened for the plasmid-mediated quinolone resistance genes of <it>qnrA</it>, <it>qnrB</it>, and <it>qnrS </it>by PCR. Transferability was examined by conjugation with the sodium azide-resistant <it>E. coli </it>J53. All <it>qnr</it>-positive were analyzed for clonality by enterobacterial repetitive intergenic consensus (ERIC)-PCR.</p> <p>Results</p> <p>The study found that 19 ciprofloxacin-resistant clinical isolates of <it>E. coli </it>and <it>K. pneumoniae </it>were positive for the <it>qnr </it>gene, and most of the <it>qnr </it>positive strains were ESBL producers. Conjugation experiments showed that quinolone resitance could be transferred to recipients. Apart from this, different DNA banding patterns were obtained by ERIC-PCR from positive strains, which means that most of them were not clonally related.</p> <p>Conclusion</p> <p>This report on transferable fluoroquinolone resistance due to the <it>qnr </it>gene among <it>E. coli </it>and <it>K. pneumoniae </it>strains indicated that plasmid-mediated quinolone resistance has emerged in pediatric patients in China.</p

Antigen-primed CD4^+CD25^+ Regulatory T Cells Prevent Skin Graft Rejection : in vitro and in vivo studies

原著論文Original PaperIn the present studies, we examined the role of regulatory T cells in developing strategies to achieve skin graft-specific tolerance and explored the immune characteristic of Treg cells and the main mechanisms through which inducing transplantation tolerance. The 5×10^4 Treg could inhibit the MLR obviously, and the effect of the Treg to the MLR is dose dependent. The suppression rate of Treg to response T cell from the donor was higher than control group that came from the non-donor, indicating that the suppression of Treg to response T cell was antigen specific. SR of Treg in co-culture was greater than that in separate culture, inferring that CD4^+CD25^+ Treg cells exerted their suppressive effects on effector T cells through cell to cell contact mechanism and cytokines secretion mechanism. In the group 1×10^5 Treg injected, the mean survive time of skin grafts from C57BL/6 mice was obviously longer than the control group. These data suggest that antigen-primed CD^4+CD25^+Treg are effective therapeutic tool to prevent skin allograft rejection