bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of Resistant
Klebsiella pneumoniae
in the Intestinal Tract during Successful Treatment of
Klebsiella pneumoniae
Lung Infection in Rats
Authors: Kesteman Anne-Sylvie , Perrin-Guyomard Agnès , Laurentie Michel , Sanders Pascal , Toutain Pierre-Louis , Bousquet-Mélou Alain 
Published: May 2010

ABSTRACT

Antibiotic treatment of lung infections may lead to the emergence of resistance in the gut flora. Appropriate dosing regimens could mitigate this adverse effect. In gnotobiotic rats harboring intestinal
Escherichia coli
and
Enterococcus faecium
populations, a lung infection by
Klebsiella pneumoniae
was instigated with two different sizes of inoculum to represent an early or a late initiation of antibiotic treatment. The rats were treated with marbofloxacin, an expanded-spectrum fluoroquinolone, by a single-shot administration or a fractionated regimen over 4 days. Intestinal bacterial populations were monitored during and after treatment. At the infection site, bacterial cure without any selection of resistance was observed. Whatever the dosage regimen, fluoroquinolone treatment had a transient negative impact on the
E. coli
gut population but not on that of
E. faecium
. The intestinal flora was colonized by the pathogenic lung bacteria, and there was the emergence of intestine-resistant
K. pneumoniae
, occurring more often in animals treated with a single marbofloxacin dose than with the fractionated dose. Bacterial cure without resistance selection at the infection site with fluoroquinolone treatment can be linked to colonization of the digestive tract by targeted pulmonary bacteria, followed by the emergence of resistance.
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions
Authors: Ge Yigong , Whitehouse M. J. , Friedland Ian , Talbot George H. 
Published: May 2010

ABSTRACT
CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or electrocardiographic finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.
Immunogenicity and Protection Induced by a
Mycobacterium tuberculosis
sigE
Mutant in a BALB/c Mouse Model of Progressive Pulmonary Tuberculosis
Authors: Pando Rogelio Hernandez , Aguilar Leon Diana , Smith Issar , Manganelli Riccardo 
Published: May 2010

ABSTRACT

Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine
Mycobacterium bovis
BCG. In this article, we analyze the potential use of an attenuated mutant of
Mycobacterium tuberculosis
H37Rv lacking the sigma factor σ
E
as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the
sigE
mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), and β-defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the
sigE
mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the
sigE
mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of
M. tuberculosis
(Beijing code 9501000). Taken together, our findings suggest that the
sigE
mutant is a very promising strain for the development of a new vaccine against tuberculosis.
Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites ofCryptosporidium parvumCellular Invasion and Facilitates Parasite Internalization
Authors: O'Hara Steven P. , Gajdos Gabriella B. , Trussoni Christy E. , Splinter Patrick L. , LaRusso Nicholas F. 
Published: May 2010

ABSTRACTInternalization of the obligate intracellular apicomplexan parasite,Cryptosporidium parvum, results in the formation of a unique intramembranous yet extracytoplasmic niche on the apical surfaces of host epithelial cells, a process that depends on host cell membrane extension. We previously demonstrated that efficientC. parvuminvasion of biliary epithelial cells (cholangiocytes) requires host cell actin polymerization and localized membrane translocation/insertion of Na+/glucose cotransporter 1 (SGLT1) and of aquaporin 1 (Aqp1), a water channel, at the attachment site. The resultant localized water influx facilitates parasite cellular invasion by promoting host-cell membrane protrusion. However, the molecular mechanisms by whichC. parvuminduces membrane translocation/insertion of SGLT1/Aqp1 are obscure. We report here that cultured human cholangiocytes express several nonmuscle myosins, including myosins IIA and IIB. Moreover,C. parvuminfection of cultured cholangiocytes results in the localized selective aggregation of myosin IIB but not myosin IIA at the region of parasite attachment, as assessed by dual-label immunofluorescence confocal microscopy. Concordantly, treatment of cells with the myosin light chain kinase inhibitor ML-7 or the myosin II-specific inhibitor blebbistatin or selective RNA-mediated repression of myosin IIB significantly inhibits (P< 0.05)C. parvumcellular invasion (by 60 to 80%). Furthermore ML-7 and blebbistatin significantly decrease (P< 0.02)C. parvum-induced accumulation of SGLT1 at infection sites (by approximately 80%). Thus, localized actomyosin-dependent membrane translocation of transporters/channels initiated byC. parvumis essential for membrane extension and parasite internalization, a phenomenon that may also be relevant to the mechanisms of cell membrane protrusion in general.
Inhibitory Effect of Needle Penetration on Vibration-Induced Finger Flexion Reflex in Humans
Authors: Takakura Nobuari , Yajima Hiroyoshi , Takayama Miho , Kawase Akiko , Homma Ikuo 
Published: May 2010

Background Vibration-induced finger flexion reflex (VFR) in the upper extremity is inhibited by needle insertion acupuncture to the large intestine 4 (LI4) at the hand. This claim has a limitation because the inhibitory effect is deduced only from reduction in the maximum finger flexion (FF) force during the tonic flexion reflex by vibratory stimulation after acupuncture. Methods The study was a crossover design with two conditions—acupuncture and control—to which 16 healthy volunteers were subjected. VFR in the upper extremity was induced by applying vibratory stimulation on the volar side of the middle fingertip of the right hand, before and after acupuncture at the right LI4 in 16 healthy volunteers. We measured the area under the curve (AUC) of finger flexion force and surface electromyogram (EMG) in the flexor muscles, in addition to the maximum FF force during vibratory stimulation. We compared AUC, surface EMG and maximum FF force in the acupuncture condition with those in the control condition. We also estimated the correlation between AUC, surface EMG and maximum FF force. Results AUC, surface EMG and maximum FF force were significantly reduced (p <0.01) after acupuncture compared with those of the control group. A strong correlation was observed in maximum FF force versus AUC (r=0.98, p <0.01) and surface EMG (r=0.77, p <0.01). Conclusions Acupuncture at ipsilateral LI4 inhibited tonic activities in the finger flexor muscles during VFR, which suggests that afferent input with needle penetration has inhibitory effect on the motor neuronal activities in the reflex circuits of VFR.
Does Needling Sensation (de qi) Affect Treatment Outcome in Pain? Analysis of Data from a Larger Single-blind, Randomised Controlled Trial
Authors: White Peter , Prescott Philip , Lewith George 
Published: May 2010

Background Insertion of an acupuncture needle into an acupuncture point typically generates a range of sensations called ‘ de qi’. Most acupuncturists are taught that obtaining de qi is important when treating patients with pain but this can be quite uncomfortable for patients. Objective This study assesses the importance of the strength of de qi, on the clinical outcome in osteoarthritic pain. Method This study was part of a larger randomised, single-blind, multifactorial trial involving three interventions: real acupuncture (RA), Streitberger needle (SN) and mock electrical stimulation for the treatment of patients with osteoarthritis (OA) of the hip and knee. Patients were treated twice a week for 4 weeks. The two outcomes relevant to this study were pain reduction assessed by visual analogue scale and the Park needling sensation questionnaire, both measured at completion of the study. Two arms of the trial were analysed (RA and SN). Reduction in pain was correlated against strength of de qi for both RA and SN. Those who felt de qi were compared with those who did not. Results 147 patients were recruited to the study (140 completed) with a mean pain reduction of 15.2 mm and mean de qi score of 6.2. There was no significant correlation between the strength of de qi and improvement in pain (p=0.49). There was also no significant difference in pain relief (p=0.52) between those who felt de qi and those who did not using the de qi subscale of the Park questionnaire. Conclusion These data suggest that the presence and intensity of de qi has no effect on the pain relief obtained for patients with OA. This result may have implications for both acupuncture treatment and for future trial methodology.
Implementation of Acupuncture and Acupressure under Surgical Procedures in Children: A Pilot Study
Authors: Norheim Arne Johan , Liodden Ingrid , Howley Michael 
Published: May 2010

Objective To test the feasibility of research on acupuncture and acupressure for children undergoing tonsillectomy and/or adenoidectomy. Methods During January and February 2008, 20 patients from the ordinary waiting list at Lovisenberg Diakonale Hospital in Oslo were randomised to either acupuncture while under anaesthesia or standard care as control. The authors gave acupuncture at Pericardium 6 (P6) at a depth of approximately 0.7 cm on both forearms. The needles were removed when the patient was transferred to the recovery unit and replaced with acupressure wristbands. The outcome measure in the pilot study was to explore if acupuncture and acupressure could be implemented without extending the anaesthesia time and surgical time. This pilot study also tested the feasibility of the research protocol for future investigation in the field, with postoperative nausea, vomiting and retching as the primary end points for effect. Results The study showed no delay in the surgical procedure and no additional anaesthesia time attributable to the introduction of acupuncture. The protocol was found to be feasible with regard to performance of the main study. Vomiting occurred in five patients in the treatment group and 10 patients in the control group. The total numbers of vomiting events were 13 in the treatment group and 19 in the control group. Conclusion The results encouraged performance of the main study according to the research protocol.
A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells
Authors: Zhou Sheng , Mody Disha , DeRavin Suk See , Hauer Julia , Lu Taihe , Ma Zhijun , Hacein-Bey Abina Salima , Gray John T. , Greene Michael R. , Cavazzana-Calvo Marina , Malech Harry L. , Sorrentino Brian P. 
Published: May 2010

Abstract
To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus. The CL20i4-hγc-Revgen vector contains the entire human common γ chain (γc) genomic sequence driven by the γc promoter. The CL20i4-EF1α-hγcOPT vector uses a promoter fragment from the eukaryotic elongation factor alpha (EF1α) gene to express a codon-optimized human γc cDNA. Both vectors contain a 400-bp insulator fragment from the chicken β-globin locus within the self-inactivating long-terminal repeat. Transduction of bone marrow cells using either of these vectors restored T, B, and natural killer lymphocyte development and function in a mouse SCID-X1 transplantation model. Transduction of human CD34+ bone marrow cells from SCID-X1 patients with either vector restored T-cell development in an in vitro assay. In safety studies using a Jurkat LMO2 activation assay, only the CL20i4-EF1α-hγcOPT vector lacked the ability to transactivate LMO2 protein expression, whereas the CL20i4-hγc-Revgen vector significantly activated LMO2 protein expression. In addition, the CL20i4-EF1α-hγcOPT vector has not caused any tumors in transplanted mice. We conclude that the CL20i4-EF1α-hγcOPT vector may be suitable for testing in a clinical trial based on these preclinical demonstrations of efficacy and safety.
Trypsin-induced proteome alteration during cell subculture in mammalian cells
Authors: Huang Hsiang-Ling , Hsing Hsiang-Wei , Lai Tzu-Chia , Chen Yi-Wen , Lee Tian-Ren , Chan Hsin-Tsu , Lyu Ping-Chiang , Wu Chieh-Lin , Lu Ying-Chieh , Lin Szu-Ting , Lin Cheng-Wen , Lai Chih-Ho , Chang Hao-Teng , Chou Hsiu-Chuan , Chan Hong-Lin 
Published: May 2010

Abstract

Background
It is essential to subculture the cells once cultured cells reach confluence. For this, trypsin is frequently applied to dissociate adhesive cells from the substratum. However, due to the proteolytic activity of trypsin, cell surface proteins are often cleaved, which leads to dysregulation of the cell functions.

Methods
In this study, a triplicate 2D-DIGE strategy has been performed to monitor trypsin-induced proteome alterations. The differentially expressed spots were identified by MALDI-TOF MS and validated by immunoblotting.

Results
36 proteins are found to be differentially expressed in cells treated with trypsin, and proteins that are known to regulate cell metabolism, growth regulation, mitochondrial electron transportation and cell adhesion are down-regulated and proteins that regulate cell apoptosis are up-regulated after trypsin treatment. Further study shows that bcl-2 is down-regulated, p53 and p21 are both up-regulated after trypsinization.

Conclusions
In summary, this is the first report that uses the proteomic approach to thoroughly study trypsin-induced cell physiological changes and provides researchers in carrying out their experimental design.
A database and API for variation, dense genotyping and resequencing data
Authors: Rios Daniel , McLaren William M , Chen Yuan , Birney Ewan , Stabenau Arne , Flicek Paul , Cunningham Fiona 
Published: May 2010

Abstract

Background
Advances in sequencing and genotyping technologies are leading to the widespread availability of multi-species variation data, dense genotype data and large-scale resequencing projects. The 1000 Genomes Project and similar efforts in other species are challenging the methods previously used for storage and manipulation of such data necessitating the redesign of existing genome-wide bioinformatics resources.

Results
Ensembl has created a database and software library to support data storage, analysis and access to the existing and emerging variation data from large mammalian and vertebrate genomes. These tools scale to thousands of individual genome sequences and are integrated into the Ensembl infrastructure for genome annotation and visualisation. The database and software system is easily expanded to integrate both public and non-public data sources in the context of an Ensembl software installation and is already being used outside of the Ensembl project in a number of database and application environments.

Conclusions
Ensembl's powerful, flexible and open source infrastructure for the management of variation, genotyping and resequencing data is freely available at http://www.ensembl.org.
eHive: An Artificial Intelligence workflow system for genomic analysis
Authors: Severin Jessica , Beal Kathryn , Vilella Albert J , Fitzgerald Stephen , Schuster Michael , Gordon Leo , Ureta-Vidal Abel , Flicek Paul , Herrero Javier 
Published: May 2010

AbstractBackgroundThe Ensembl project produces updates to its comparative genomics resources with each of its several releases per year. During each release cycle approximately two weeks are allocated to generate all the genomic alignments and the protein homology predictions. The number of calculations required for this task grows approximately quadratically with the number of species. We currently support 50 species in Ensembl and we expect the number to continue to grow in the future.ResultsWe present eHive, a new fault tolerant distributed processing system initially designed to support comparative genomic analysis, based on blackboard systems, network distributed autonomous agents, dataflow graphs and block-branch diagrams. In the eHive system a MySQL database serves as the central blackboard and the autonomous agent, a Perl script, queries the system and runs jobs as required. The system allows us to define dataflow and branching rules to suit all our production pipelines. We describe the implementation of three pipelines: (1) pairwise whole genome alignments, (2) multiple whole genome alignments and (3) gene trees with protein homology inference. Finally, we show the efficiency of the system in real case scenarios.ConclusionseHive allows us to produce computationally demanding results in a reliable and efficient way with minimal supervision and high throughput. Further documentation is available at:http://www.ensembl.org/info/docs/eHive/.
Error margin analysis for feature gene extraction
Authors: Chow Chi Kin , Zhu Hai Long , Lacy Jessica , Kuo Winston P 
Published: May 2010

Abstract

Background
Feature gene extraction is a fundamental issue in microarray-based biomarker discovery. It is normally treated as an optimization problem of finding the best predictive feature genes that can effectively and stably discriminate distinct types of disease conditions, e.g. tumors and normals. Since gene microarray data normally involves thousands of genes at, tens or hundreds of samples, the gene extraction process may fall into local optimums if the gene set is optimized according to the maximization of classification accuracy of the classifier built from it.

Results
In this paper, we propose a novel gene extraction method of error margin analysis to optimize the feature genes. The proposed algorithm has been tested upon one synthetic dataset and two real microarray datasets. Meanwhile, it has been compared with five existing gene extraction algorithms on each dataset. On the synthetic dataset, the results show that the feature set extracted by our algorithm is the closest to the actual gene set. For the two real datasets, our algorithm is superior in terms of balancing the size and the validation accuracy of the resultant gene set when comparing to other algorithms.

Conclusion
Because of its distinct features, error margin analysis method can stably extract the relevant feature genes from microarray data for high-performance classification.
The long noncoding RNA RNCR2 directs mouse retinal cell specification
Authors: Rapicavoli Nicole A , Poth Erin M , Blackshaw Seth 
Published: May 2010

Abstract

Background
Recent work has identified that many long mRNA-like noncoding RNAs (lncRNAs) are expressed in the developing nervous system. Despite their abundance, the function of these ncRNAs has remained largely unexplored. We have investigated the highly abundant lncRNA RNCR2 in regulation of mouse retinal cell differentiation.

Results
We find that the RNCR2 is selectively expressed in a subset of both mitotic progenitors and postmitotic retinal precursor cells. ShRNA-mediated knockdown of RNCR2 results in an increase of both amacrine cells and Müller glia, indicating a role for this lncRNA in regulating retinal cell fate specification. We further report that RNCR2 RNA, which is normally nuclear-retained, can be exported from the nucleus when fused to an IRES-GFP sequence. Overexpression of RNCR2-IRES-GFP phenocopies the effects of shRNA-mediated knockdown of RNCR2, implying that forced mislocalization of RNCR2 induces a dominant-negative phenotype. Finally, we use the IRES-GFP fusion approach to identify specific domains of RNCR2 that are required for repressing both amacrine and Müller glial differentiation.

Conclusion
These data demonstrate that the lncRNA RNCR2 plays a critical role in regulating mammalian retinal cell fate specification. Furthermore, we present a novel approach for generating dominant-negative constructs of lncRNAs, which may be generally useful in the functional analysis of this class of molecules.