bluuebunny/crossref_metadata_2025_split huggingface dataset:
α1-antitrypsin promotes SPLUNC1-mediated lung defense against Pseudomonas aeruginosa infection in mice
Authors: Jiang Di , Persinger Rebecca , Wu Qun , Gross Ashley , Chu Hong Wei 
Published: November 2013

Abstract

Background

Pseudomonas aeruginosa (PA) infection is involved in various lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. However, treatment of PA infection is not very effective in part due to antibiotic resistance. α1-antitrypsin (A1AT) has been shown to reduce PA infection in humans and animals, but the underlying mechanisms remain unclear. The goal of our study is to test whether a novel endogenous host defense protein, short palate, lung, and nasal epithelium clone 1 (SPLUNC1), is involved in the therapeutic effect of A1AT during lung PA infection.

Method
SPLUNC1 knockout (KO) and littermate wild-type (WT) mice on the C57BL/6 background were intranasally infected with PA to determine the therapeutic effects of A1AT. A1AT was aerosolized to mice 2 hrs after the PA infection, and mice were sacrificed 24 hrs later. PA load and inflammation were quantified in the lung, and SPLUNC1 protein in bronchoalveolar lavage (BAL) fluid was examined by Western blot.

Results
In WT mice, PA infection significantly increased neutrophil elastase (NE) activity, but reduced SPLUNC1 protein in BAL fluid. Notably, PA-infected mice treated with A1AT versus bovine serum albumin (BSA) demonstrated higher levels of SPLUNC1 protein expression, which are accompanied by lower levels of NE activity, lung bacterial load, and pro-inflammatory cytokine production. To determine whether A1AT therapeutic effects are dependent on SPLUNC1, lung PA load in A1AT- or BSA-treated SPLUNC1 KO mice was examined. Unlike the WT mice, A1AT treatment in SPLUNC1 KO mice had no significant impact on lung PA load and pro-inflammatory cytokine production.

Conclusion
A1AT reduces lung bacterial infection in mice in part by preventing NE-mediated SPLUNC1 degradation.
Evolutionary rate patterns of genes involved in the Drosophila Toll and Imd signaling pathway
Authors: Han Ming , Qin Sheng , Song Xiaojun , Li Yafang , Jin Ping , Chen Liming , Ma Fei 
Published: November 2013

AbstractBackgroundTo survive in a hostile environment, insects have evolved an innate immune system to defend against infection. Studies have shown that natural selection may drive the evolution of immune system-related proteins. Yet, how network architecture influences protein sequence evolution remains unclear. Here, we analyzed the molecular evolutionary patterns of genes in the Toll and Imd innate immune signaling pathways across sixDrosophilagenomes within the context of a functional network.ResultsBased on published literature, we identified 50 genes that are directly involved in theDrosophilaToll and Imd signaling pathways. Of those genes, only two (Sphinx1andDnr1) exhibited signals of positive selection. There existed a negative correlation between the strength of purifying selection and gene position within the pathway; the downstream genes were more conserved, indicating that they were subjected to stronger evolutionary constraints. Interestingly, there was also a significantly negative correlation between the rate of protein evolution and the number of regulatory microRNAs, implying that genes regulated by more miRNAs experience stronger functional constraints and therefore evolve more slowly.ConclusionTaken together, our results suggested that both network architecture and miRNA regulation affect protein sequence evolution. These findings improve our understanding of the evolutionary patterns of genes involved inDrosophilainnate immune pathways.
Medium-sized tandem repeats represent an abundant component of the Drosophila virilis genome
Authors: Abdurashitov Murat A , Gonchar Danila A , Chernukhin Valery A , Tomilov Victor N , Tomilova Julia E , Schostak Natalia G , Zatsepina Olga G , Zelentsova Elena S , Evgen’ev Michael B , Degtyarev Sergey Kh 
Published: November 2013

Abstract

Background
Previously, we developed a simple method for carrying out a restriction enzyme analysis of eukaryotic DNA in silico, based on the known DNA sequences of the genomes. This method allows the user to calculate lengths of all DNA fragments that are formed after a whole genome is digested at the theoretical recognition sites of a given restriction enzyme. A comparison of the observed peaks in distribution diagrams with the results from DNA cleavage using several restriction enzymes performed in vitro have shown good correspondence between the theoretical and experimental data in several cases. Here, we applied this approach to the annotated genome of Drosophila virilis which is extremely rich in various repeats.

Results
Here we explored the combined approach to perform the restriction analysis of D. virilis DNA. This approach enabled to reveal three abundant medium-sized tandem repeats within the D. virilis genome. While the 225 bp repeats were revealed previously in intergenic non-transcribed spacers between ribosomal genes of D. virilis, two other families comprised of 154 bp and 172 bp repeats were not described. Tandem Repeats Finder search demonstrated that 154 bp and 172 bp units are organized in multiple clusters in the genome of D. virilis. Characteristically, only 154 bp repeats derived from Helitron transposon are transcribed.

Conclusion
Using in silico digestion in combination with conventional restriction analysis and sequencing of repeated DNA fragments enabled us to isolate and characterize three highly abundant families of medium-sized repeats present in the D. virilis genome. These repeats comprise a significant portion of the genome and may have important roles in genome function and structural integrity. Therefore, we demonstrated an approach which makes possible to investigate in detail the gross arrangement and expression of medium-sized repeats basing on sequencing data even in the case of incompletely assembled and/or annotated genomes.
Neisseria gonorrhoeae PIII has a role on NG1873 outer membrane localization and is involved in bacterial adhesion to human cervical and urethral epithelial cells
Authors: Leuzzi Rosanna , Nesta Barbara , Monaci Elisabetta , Cartocci Elena , Serino Laura , Soriani Marco , Rappuoli Rino , Pizza Mariagrazia 
Published: November 2013

Abstract

Background
Protein PIII is one of the major outer membrane proteins of Neisseria gonorrhoeae, 95% identical to RmpM (reduction modifiable protein M) or class 4 protein of Neisseria meningitidis. RmpM is known to be a membrane protein associated by non-covalent bonds to the peptidoglycan layer and interacting with PorA/PorB porin complexes resulting in the stabilization of the bacterial membrane. The C-terminal domain of PIII (and RmpM) is highly homologous to members of the OmpA family, known to have a role in adhesion/invasion in many bacterial species. The contribution of PIII in the membrane architecture and its role in the interaction with epithelial cells has never been investigated.

Results
We generated a ΔpIII knock-out mutant strain and evaluated the effects of the loss of PIII expression on bacterial morphology and on outer membrane composition. Deletion of the pIII gene does not cause any alteration in bacterial morphology or sensitivity to detergents. Moreover, the expression profile of the main membrane proteins remains the same for the wild-type and knock-out strains, with the exception of the NG1873 which is not exported to the outer membrane and accumulates in the inner membrane in the ΔpIII knock-out mutant strain.
We also show that purified PIII protein is able to bind human cervical and urethral cells and that the ΔpIII knock-out mutant strain has a lower ability to adhere to human cervical and urethral cells.

Conclusion
Here we demonstrated that the PIII protein does not play a key structural role in the membrane organization of gonococcus and does not induce major effects on the expression of the main outer membrane proteins. However, in the PIII knock-out strain, the NG1873 protein is not localized in the outer membrane as it is in the wild-type strain suggesting a possible interaction of PIII with NG1873. The evidence that PIII binds to human epithelial cells derived from the female and male genital tract highlights a possible role of PIII in the virulence of gonococcus and suggests that the structural homology to OmpA is conserved also at functional level.
FACET – a “Flexible Artifact Correction and Evaluation Toolbox” for concurrently recorded EEG/fMRI data
Authors: Glaser Johann , Beisteiner Roland , Bauer Herbert , Fischmeister Florian Ph S 
Published: November 2013

AbstractBackgroundIn concurrent EEG/fMRI recordings, EEG data are impaired by the fMRI gradient artifacts which exceed the EEG signal by several orders of magnitude. While several algorithms exist to correct the EEG data, these algorithms lack the flexibility to either leave out or add new steps. The here presented open-source MATLAB toolbox FACET is a modular toolbox for the fast and flexible correction and evaluation of imaging artifacts from concurrently recorded EEG datasets. It consists of anAnalysis, aCorrectionand anEvaluationframework allowing the user to choose from different artifact correction methods with various pre- and post-processing steps to form flexible combinations. The quality of the chosen correction approach can then be evaluated and compared to different settings.ResultsFACET was evaluated on a dataset provided with the FMRIB plugin for using two different correction approaches: Averaged Artifact Subtraction (AAS, Allen et al., NeuroImage 12(2):230–239, 2000) and the FMRI Artifact Slice Template Removal (FASTR, Niazy et al., NeuroImage 28(3):720–737, 2005). Evaluation of the obtained results were compared to the FASTR algorithm implemented in the plugin FMRIB. No differences were found between the FACET implementation of FASTR and the original algorithm across all gradient artifact relevant performance indices.ConclusionThe FACET toolbox not only provides facilities for all three modalities: data analysis, artifact correction as well as evaluation and documentation of the results but it also offers an easily extendable framework for development and evaluation of new approaches.
Mapping the interactome of overexpressed RAF kinase inhibitor protein in a gastric cancer cell line
Authors: Gu Huan , Zhan Xianquan , Zhang Guiying , Yan Lu , Cho William CS , Li Maoyu , Liu Ting , Chen Zhuchu 
Published: November 2013

Abstract

Background
Gastric cancer (GC) is a threat to human health with increasing incidence and mortality worldwide. Down-regulation or absence of RAF kinase inhibitor protein (RKIP) was associated with the occurrence, differentiation, invasion, and metastasis of GC. This study aims to investigate the molecular mechanisms and biological functions of RKIP in the GC biology.

Methods
The fusion expression plasmid pcDNA3.1-RKIP-3xFLAG was transfected into SGC7901 cells, the RKIP fusion proteins were purified with anti-flag M2 magnetic beads, and the RKIP-interacting proteins were identified with tandem mass spectrometry (MS/MS), and were analyzed with bioinformatics tools. Western blot and co-immunoprecipitation were used to confirm the interaction complex.

Results
A total of 72 RKIP-interacting proteins were identified by MS/MS. Those proteins play roles in enzyme metabolism, molecular chaperoning, biological oxidation, cytoskeleton organization, signal transduction, and enzymolysis. Three RKIP-interaction protein network diagrams were constructed with Michigan Molecular Interactions, functional linage network, and Predictome analysis to address the molecular pathways of the functional activity of RKIP. The MS/MS-characterized components of the existing interaction complex (RKIP, HSP90, 14-3-3ϵ, and keratin 8) were confirmed by Western blot analysis and co-immunoprecipitation.

Conclusion
This study is the first discovery of the interaction of RKIP with HSP90, 14-3-3, and keratin. The present data would provide insight into the molecular mechanisms of how RKIP inhibits the occurrence and development of GC.
Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study
Authors: Concerto Carmen , Lanza Giuseppe , Cantone Mariagiovanna , Pennisi Manuela , Giordano Daniela , Spampinato Concetto , Ricceri Riccardo , Pennisi Giovanni , Aguglia Eugenio , Bella Rita 
Published: November 2013

AbstractBackgroundClinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD.MethodsEleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study.ResultsScores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls.ConclusionsThis study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the “Vascular depression hypothesis” at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug-induced effect on our results cannot be excluded. This study may aid the understanding of the pathogenetic differences underlying the clinical spectrum of depressive disorders.
Development of a new pre-vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nano-hydroxyapatide-polyamide 66 scaffold
Authors: Yang Pei , Huang Xin , Shen Jacson , Wang Chunsheng , Dang Xiaoqian , Mankin Henry , Duan Zhenfeng , Wang Kunzheng 
Published: November 2013

Abstract

Background
Development of a pre-vascularized tissue-engineered construct with intrinsic vascular system for cell growth and tissue formation still faces many difficulties due to the complexity of the vascular network of natural bone tissue. The present study was to design and form a new vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nHA-PA 66 scaffold.

Methods
rADSCs were pre-differentiated to endothelial cells (rADSCs-Endo) and then incorporated in nHA-PA 66 scaffolds in vitro. Subsequently, in vivo experiments were carried out according to the following groups: Group A (rADSCs-Endo/nHA-PA 66 scaffold with arteriovenous vascular bundle), Group B (rADSCs/nHA-PA 66 scaffold with arteriovenous vascular bundle); Group C (nHA-PA66 scaffold with arteriovenous vascular bundle), Group D (nHA-PA 66 scaffold only). The vessel density and vessel diameter were measured based on histological and immunohistochemical evaluation, furthermore, the VEGF-C, FGF-2 and BMP-2 protein expressions were also evaluated by western blot analysis.

Results
The results of in vivo experiments showed that the vessel density and vessel diameter in group A were significantly higher than the other three groups. Between Group B and C, no statistical difference was observed at each time point. In accordance with the results, there were dramatically higher expressions of VEGF-C and FGF-2 protein in Group A than that of Group B, C and D at 2 or 4 weeks. Statistical differences were not observed in VEGF-C and FGF-2 expression between Group B and C. BMP-2 was not expressed in any group at each time point.

Conclusions
Compared with muscular wrapping method, arteriovenous vascular bundle implantation could promote vascularization of the scaffold; and the angiogenesis of the scaffold was significantly accelerated when pre-differentiated rADSCs (endothelial differentiation) were added. These positive results implicate the combination of pre-differentiated rADSCs (endothelial differentiation) and arteriovenous vascular bundle may achieve rapidly angiogenesis of biomaterial scaffold.
Effect of intracellular loop 3 on intrinsic dynamics of human β2-adrenergic receptor
Authors: Ozcan Ozer , Uyar Arzu , Doruker Pemra , Akten Ebru Demet 
Published: November 2013

Abstract

Background
To understand the effect of the long intracellular loop 3 (ICL3) on the intrinsic dynamics of human β2-adrenergic receptor, molecular dynamics (MD) simulations were performed on two different models, both of which were based on the inactive crystal structure in complex with carazolol (after removal of carazolol and T4-lysozyme). In the so-called loop model, the ICL3 region that is missing in available crystal structures was modeled as an unstructured loop of 32-residues length, whereas in the clipped model, the two open ends were covalently bonded to each other. The latter model without ICL3 was taken as a reference, which has also been commonly used in recent computational studies. Each model was embedded into POPC bilayer membrane with explicit water and subjected to a 1 μs molecular dynamics (MD) simulation at 310 K.

Results
After around 600 ns, the loop model started a transition to a “very inactive” conformation, which is characterized by a further movement of the intracellular half of transmembrane helix 6 (TM6) towards the receptor core, and a close packing of ICL3 underneath the membrane completely blocking the G-protein’s binding site. Concurrently, the binding site at the extracellular part of the receptor expanded slightly with the Ser207-Asp113 distance increasing to 18 Å from 11 Å, which was further elaborated by docking studies.

Conclusions
The essential dynamics analysis indicated a strong coupling between the extracellular and intracellular parts of the intact receptor, implicating a functional relevance for allosteric regulation. In contrast, no such transition to the “very inactive” state, nor any structural correlation, was observed in the clipped model without ICL3. Furthermore, elastic network analysis using different conformers for the loop model indicated a consistent picture on the specific ICL3 conformational change being driven by global modes.
RETRACTED ARTICLE: Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia-reperfusion injury in rats is linked with inhibition of cyclin-dependent kinase 5
Authors: Wang Lei , Jiang Dian-Ming 
Published: November 2013

Abstract
Background
Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, has been shown to exert a variety of pharmacological effects including neuroprotective properties. However, the mechanism of neuroprotection is not fully understood. This study was designed to explore the mechanism of BYHWD in the treatment of spinal ischemia-reperfusion injury in rats.

Methods
Twenty-eight male Sprague–Dawley rats, weighting 250–280 g, were used, and were randomly divided into four groups with 7 animals in each: sham operation group (Control), spinal ischemia with saline (SI + Saline), spinal ischemia with BYHWD (SI + BYHWD), and spinal ischemia with roscovitine (SI + R). After 60 minutes of spinal ischemia followed by 72 hours of reperfusion, motor function of hind limbs, spinal ischemic infarction volume, the number of apoptotic cells, and cyclin-dependent kinase 5 (Cdk5) were examined.

Result
Ischemia-reperfusion resulted in injury of the spines, while BYHWD significantly improved spinal function. The spinal infarction volume, number of apoptotic cells, and Cdk5 were decreased by administration of BYHWD. The similar improvements were seen with the pre-treatment of roscovitine.

Conclusions
BYHWD prevented the ischemia-reperfusion-induced spinal injury in rats. The protective function of BYHWD was, in part, linked with inhibition of Cdk5.
A comparison of calibration data from full field digital mammography units for breast density measurements
Authors: Fowler Erin EE , Lu Beibei , Heine John J 
Published: November 2013

Abstract

Background
Breast density is a significant breast cancer risk factor measured from mammograms. The most appropriate method for measuring breast density for risk applications is still under investigation. Calibration standardizes mammograms to account for acquisition technique differences prior to making breast density measurements. We evaluated whether a calibration methodology developed for an indirect x-ray conversion full field digital mammography (FFDM) technology applies to direct x-ray conversion FFDM systems.

Methods
Breast tissue equivalent (BTE) phantom images were used to establish calibration datasets for three similar direct x-ray conversion FFDM systems. The calibration dataset for each unit is a function of the target/filter combination, x-ray tube voltage, current × time (mAs), phantom height, and two detector fields of view (FOVs). Methods were investigated to reduce the amount of calibration data by restricting the height, mAs, and FOV sampling. Calibration accuracy was evaluated with mixture phantoms. We also compared both intra- and inter-system calibration characteristics and accuracy.

Results
Calibration methods developed previously apply to direct x-ray conversion systems with modification. Calibration accuracy was largely within the acceptable range of ± 4 standardized units from the ideal value over the entire acquisition parameter space for the direct conversion units. Acceptable calibration accuracy was maintained with a cubic-spline height interpolation, representing a modification to previous work. Calibration data is unit specific, can be acquired with the large FOV, and requires a minimum of one reference mAs sample. The mAs sampling, calibration accuracy, and the necessity for machine specific calibration data are common characteristics and in agreement with our previous work.

Conclusion
The generality of our calibration approach was established under ideal conditions. Evaluation with patient data using breast cancer status as the endpoint is required to demonstrate that the approach produces a breast density measure associated with breast cancer.