bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simian virus 40 vectors for pulmonary gene therapy
Authors: Eid Luminita , Bromberg Zohar , EL-Latif Mahmoud Abd , Zeira Evelyn , Oppenheim Ariella , Weiss Yoram G 
Published: October 2007

Abstract

Background
Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy.

Methods
Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector.

Results
Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response.

Conclusion
In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.
A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments
Authors: Robinson Mark D , De Souza David P , Keen Woon Wai , Saunders Eleanor C , McConville Malcolm J , Speed Terence P , Likić Vladimir A 
Published: October 2007

Abstract

Background
Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies.

Results
A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites.

Conclusion
We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.
Functional genomic delineation of TLR-induced transcriptional networks
Authors: Elkon Ran , Linhart Chaim , Halperin Yonit , Shiloh Yosef , Shamir Ron 
Published: October 2007

AbstractBackgroundThe innate immune system is the first line of defense mechanisms protecting the host from invading pathogens such as bacteria and viruses. The innate immunity responses are triggered by recognition of prototypical pathogen components by cellular receptors. Prominent among these pathogen sensors are Toll-like receptors (TLRs). We sought global delineation of transcriptional networks induced by TLRs, analyzing four genome-wide expression datasets in mouse and human macrophages stimulated with pathogen-mimetic agents that engage various TLRs.ResultsCombining computational analysis of expression profiles and cis-regulatory promoter sequences, we dissected the TLR-induced transcriptional program into two major components: the first is universally activated by all examined TLRs, and the second is specific to activated TLR3 and TLR4. Our results point to NF-κB and ISRE-binding transcription factors as the key regulators of the universal and the TLR3/4-specific responses, respectively, and identify novel putative positive and negative feedback loops in these transcriptional programs. Analysis of the kinetics of the induced network showed that while NF-κB regulates mainly an early-induced and sustained response, the ISRE element functions primarily in the induction of a delayed wave. We further demonstrate that co-occurrence of the NF-κB and ISRE elements in the same promoter endows its targets with enhanced responsiveness.ConclusionOur results enhance system-level understanding of the networks induced by TLRs and demonstrate the power of genomics approaches to delineate intricate transcriptional webs in mammalian systems. Such systems-level knowledge of the TLR network can be useful for designing ways to pharmacologically manipulate the activity of the innate immunity in pathological conditions in which either enhancement or repression of this branch of the immune system is desired.
Genome-wide survey of putative Serine/Threonine protein kinases in cyanobacteria
Authors: Zhang Xiaowen , Zhao Fangqing , Guan Xiangyu , Yang Yu , Liang Chengwei , Qin Song 
Published: October 2007

Abstract

Background
Serine/threonine kinases (STKs) have been found in an increasing number of prokaryotes, showing important roles in signal transduction that supplement the well known role of two-component system. Cyanobacteria are photoautotrophic prokaryotes able to grow in a wide range of ecological environments, and their signal transduction systems are important in adaptation to the environment. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of this kinase family. In this study, we extracted information regarding Ser/Thr kinases from 21 species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution.

Results
286 putative STK homologues were identified. STKs are absent in four Prochlorococcus strains and one marine Synechococcus strain and abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic STKs were conserved well in these proteins, and six more cyanobacteria- or bacteria-specific conserved residues were found. These STK proteins were classified into three major families according to their domain structures. Fourteen types and a total of 131 additional domains were identified, some of which are reported to participate in the recognition of signals or substrates. Cyanobacterial STKs show rather complicated phylogenetic relationships that correspond poorly with phylogenies based on 16S rRNA and those based on additional domains.

Conclusion
The number of STK genes in different cyanobacteria is the result of the genome size, ecophysiology, and physiological properties of the organism. Similar conserved motifs and amino acids indicate that cyanobacterial STKs make use of a similar catalytic mechanism as eukaryotic STKs. Gene gain-and-loss is significant during STK evolution, along with domain shuffling and insertion. This study has established an overall framework of sequence-structure-function interactions for the STK gene family, which may facilitate further studies of the role of STKs in various organisms.
Comparative genomic analysis of two-component regulatory proteins in Pseudomonas syringae
Authors: Lavín José L , Kiil Kristoffer , Resano Ohiana , Ussery David W , Oguiza José A 
Published: October 2007

AbstractBackgroundPseudomonas syringaeis a widespread bacterial plant pathogen, and strains ofP. syringaemay be assigned to different pathovars based on host specificity among different plant species. The genomes ofP. syringaepv.syringae(Psy) B728a, pv.tomato(Pto) DC3000 and pv.phaseolicola(Pph) 1448A have been recently sequenced providing a major resource for comparative genomic analysis. A mechanism commonly found in bacteria for signal transduction is the two-component system (TCS), which typically consists of a sensor histidine kinase (HK) and a response regulator (RR).P. syringaerequires a complex array of TCS proteins to cope with diverse plant hosts, host responses, and environmental conditions.ResultsBased on the genomic data, pattern searches with Hidden Markov Model (HMM) profiles have been used to identify putative HKs and RRs. The genomes ofPsyB728a,PtoDC3000 andPph1448A were found to contain a large number of genes encoding TCS proteins, and a core of complete TCS proteins were shared between these genomes: 30 putative TCS clusters, 11 orphan HKs, 33 orphan RRs, and 16 hybrid HKs. A close analysis of the distribution of genes encoding TCS proteins revealed important differences in TCS proteins among the threeP. syringaepathovars.ConclusionIn this article we present a thorough analysis of the identification and distribution of TCS proteins among the sequenced genomes ofP. syringae. We have identified differences in TCS proteins among the threeP. syringaepathovars that may contribute to their diverse host ranges and association with plant hosts. The identification and analysis of the repertoire of TCS proteins in the genomes ofP. syringaepathovars constitute a basis for future functional genomic studies of the signal transduction pathways in this important bacterial phytopathogen.
Global transcriptional response of Escherichia coli O157:H7 to growth transitions in glucose minimal medium
Authors: Bergholz Teresa M , Wick Lukas M , Qi Weihong , Riordan James T , Ouellette Lindsey M , Whittam Thomas S 
Published: October 2007

Abstract

Background:
Global patterns of gene expression of Escherichia coli K-12 during growth transitions have been deeply investigated, however, comparable studies of E. coli O157:H7 have not been explored, particularly with respect to factors regulating virulence genes and genomic islands specific to this pathogen. To examine the impact of growth phase on the dynamics of the transcriptome, O157:H7 Sakai strain was cultured in MOPS minimal media (0.1% glucose), RNA harvested at 10 time points from early exponential to full stationary phase, and relative gene expression was measured by co-hybridization on high-density DNA microarrays. Expression levels of 14 genes, including those encoding Shiga toxins and other virulence factors associated with the locus of enterocyte effacement (LEE), were confirmed by Q-PCR.

Results:
Analysis of variance (R/MAANOVA, Fs test) identified 442 (36%) of 1239 O157-specific ORFs and 2110 (59%) of 3647 backbone ORFs that changed in expression significantly over time. QT cluster analysis placed 2468 of the 2552 significant ORFs into 12 groups; each group representing a distinct expression pattern. ORFs from the largest cluster (n = 1078) decreased in expression from late exponential to early stationary phase: most of these ORFs are involved in functions associated with steady state growth. Also represented in this cluster are ORFs of the TAI island, encoding tellurite resistance and urease activity, which decreased ~4-fold. Most ORFs of the LEE pathogenicity island also decreased ~2-fold by early stationary phase. The ORFs encoding proteins secreted via the LEE encoded type III secretion system, such as tccP and espJ, also decreased in expression from exponential to stationary phase. Three of the clusters (n = 154) comprised genes that are transiently upregulated at the transition into stationary phase and included genes involved in nutrient scavenging. Upregulated genes with an increase in mRNA levels from late exponential to early stationary phase belonged to one cluster (n = 923) which includes genes involved in stress responses (e.g. gadAB, osmBC, and dps). These transcript levels remained relatively high for > 3 h in stationary phase. The Shiga toxin genes (stx 1AB and stx 2B) were significantly induced after transition into stationary phase.

Conclusion:
Expression of more than 300 O157-specific ORFs, many implicated in virulence of the O157 pathogen, was modulated in a growth dependent manner. These results provide a baseline transcriptional profile that can be compared to patterns of gene expression of this important foodborne pathogen under adverse environmental conditions.
Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms
Authors: Mellmann Alexander , Weniger Thomas , Berssenbrügge Christoph , Rothgänger Jörg , Sammeth Michael , Stoye Jens , Harmsen Dag 
Published: October 2007

Abstract

Background
For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types.
For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC) were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544).

Results
In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates) and 33 singletons (46 isolates). BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index) and spa-CCs gave a concordance of 87.1%; BURP spa-CCs vs. manually grouped spa types resulted in 95.7% concordance.

Conclusion
BURP is the first automated and objective tool to infer clonal relatedness from spa repeat regions. It is able to extract an evolutionary signal rather congruent to MLST and micro-array data.
The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion
Authors: Pellissier François , Gerber Alan , Bauer Christoph , Ballivet Marc , Ossipow Vincent 
Published: October 2007

Abstract

Background
Cell adhesion molecules are plasma membrane proteins specialized in cell-cell recognition and adhesion. Two related adhesion molecules, Necl-1 and Necl-2/SynCAM, were recently described and shown to fulfill important functions in the central nervous system. The purpose of the work was to investigate the distribution, and the properties of Necl-3/SynCAM-2, a previously uncharacterized member of the Necl family with which it shares a conserved modular organization and extensive sequence homology.

Results
We show that Necl-3/SynCAM-2 is a plasma membrane protein that accumulates in several tissues, including those of the central and peripheral nervous system. There, Necl-3/SynCAM-2 is expressed in ependymal cells and in myelinated axons, and sits at the interface between the axon shaft and the myelin sheath. Several independent assays demonstrate that Necl-3/SynCAM-2 functionally and selectively interacts with oligodendrocytes. We finally prove that Necl-3/SynCAM-2 is a bona fide adhesion molecule that engages in homo- and heterophilic interactions with the other Necl family members, leading to cell aggregation.

Conclusion
Collectively, our manuscripts and the works on Necl-1 and SynCAM/Necl-2 reveal a complex set of interactions engaged in by the Necl proteins in the nervous system. Our work also support the notion that the family of Necl proteins fulfils key adhesion and recognition functions in the nervous system, in particular between different cell types.
Costs and consequences of treatment for mild gestational diabetes mellitus – evaluation from the ACHOIS randomised trial
Authors: Moss John R , Crowther Caroline A , Hiller Janet E , Willson Kristyn J , Robinson Jeffrey S ,   The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group
Published: October 2007

Abstract

Background
Recommended best practice is that economic evaluation of health care interventions should be integral with randomised clinical trials. We performed a cost-consequence analysis of treating women with mild gestational diabetes mellitus by dietary advice, blood glucose monitoring and insulin therapy as needed compared with routine pregnancy care, using patient-level data from a multi-centre randomised clinical trial.

Methods
Women with a singleton pregnancy who had mild gestational diabetes diagnosed by an oral glucose-tolerance test between 24 and 34 weeks' gestation and their infants were included. Clinical outcomes and outpatient costs derived from all women and infants in the trial. Inpatient costs derived from women and infants attending the hospital contributing the largest number of enrolments (26.1%), and charges to women and their families derived from a subsample of participants from that hospital (in 2002 Australian dollars). Occasions of service and health outcomes were adjusted for maternal age, ethnicity and parity. Analysis of variance was used with bootstrapping to confirm results. Primary clinical outcomes were serious perinatal complications; admission to neonatal nursery; jaundice requiring phototherapy; induction of labour and caesarean delivery. Economic outcome measures were outpatient and inpatient costs, and charges to women and their families.

Results
For every 100 women with a singleton pregnancy and positive oral glucose tolerance test who were offered treatment for mild gestational diabetes mellitus in addition to routine obstetric care, $53,985 additional direct costs were incurred at the obstetric hospital, $6,521 additional charges were incurred by women and their families, 9.7 additional women experienced induction of labour, and 8.6 more babies were admitted to a neonatal nursery. However, 2.2 fewer babies experienced serious perinatal complication and 1.0 fewer babies experienced perinatal death. The incremental cost per additional serious perinatal complication prevented was $27,503, per perinatal death prevented was $60,506 and per discounted life-year gained was $2,988.

Conclusion
It is likely that the general public in high-income countries such as Australia would find reductions in perinatal mortality and in serious perinatal complications sufficient to justify additional health service and personal monetary charges. Over the whole lifespan, the incremental cost per extra life-year gained is highly favourable.

Trial Registration
Australian Clinical Trials Registry ACTRN12606000294550
Reliability of lumbar spinal palpation, range of motion, and determination of position
Authors: Troke Michael , Schuit Dale , Petersen Cheryl M 
Published: October 2007

Abstract

Background
The study purposes were to investigate the level of agreement of palpation of lumbar spinous processes between examiners, test-retest repeatability of lumbar spine range of motion, and the reliability of upright position measures in asymptomatic subjects.

Methods
The modified CA 6000 spinal motion apparatus with a new skin fixation system was used by three operators for the test-retest spine measurements (3 days apart), and to obtain measures at one session of spinal position. Mean ranges of motion in all planes for 22 asymptomatic subjects were reported using the Intra-class Correlation Coefficient.

Results
Overall, differences in palpation agreement for lumbar segments occurred in three subjects and did not affect range of motion values. For upright spinal position, ICC (2,3) values for sagittal, coronal, and horizontal plane positions were 0.96, 0.80, and 0.98 respectively. There were statistically significant differences between examiners for position values, determined by the Bonferroni t-test (p < 0.05), but the magnitude of the differences were 2 degrees or less, and not considered clinically important.

Conclusion
Results suggest that lumbar spinal motion measurements and position determination between different operators can be consistent particularly if utilizing the modified instrument. Static lumbar position also appears to be recorded reliably between different operators. Results justify progression to multi-center lumbar research using the modified CA 6000 and the work is considered relevant to medical clinicians working with spinal dysfunction, surgical interventions, or occupational health.