bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Persistent Wave Groups
Authors: Smith Jerome A. , Brulefert Coralie 
Published: August 2009

Abstract
During the near-field leg of the Hawaiian Ocean-Mixing Experiment (HOME-NF), short, steep surface wave groups were observed that elicited strong group-forced responses in the wave-filtered surface current field, as reported by Smith. Some of these wave groups persisted for 17 wave periods, yet were only about 1 wavelength long in the along-wind direction. Here, the authors consider the evolution of wave groups of the form observed and find that this persistence is consistent with linear dispersion in spite of the very compact form. The key aspects enhancing persistence are 1) that the wave crests within the group are oriented at an angle with respect to the group envelope and 2) they are much wider in the crosswind direction than along-wind (in the example examined in detail, about 5 times). According to a simplified model, groups with the observed 5-to-1 aspect ratio and this “slant-wave” structure can persist for up to 20 wave periods, consistent with the observations (cf. 8 periods for a collinear wave group). The maximum persistence increases in proportion to the across-wind length of the group.
Patellar Tendon Versus Hamstring Tendon Autografts for Reconstructing the Anterior Cruciate Ligament
Authors: Biau David Jean , Katsahian Sandrine , Kartus Jüri , Harilainen Arsi , Feller Julian A. , Sajovic Matjaz , Ejerhed Lars , Zaffagnini Stefano , Röpke Martin , Nizard Rémy 
Published: August 2009

Background The best means of ensuring knee stability after anterior cruciate ligament (ACL) reconstruction remains a core debate in sports medicine. Hypothesis There is no difference between ACL reconstruction with patellar tendon or hamstring tendon autografts with regard to postoperative knee laxity and instability. Study Design Meta-analysis of individual patient data. Methods Pooled analysis of individual patient data from 6 published randomized clinical trials included 423 patients with symptomatic unilateral anterior cruciate ligament injury randomly assigned to reconstruction with patellar tendon or hamstring tendon autograft. Knee instability, defined as a positive pivot-shift test result, was the primary outcome, and knee laxity, defined as a positive Lachman test result, was the secondary outcome. Odds ratios were computed before and after adjustment for potential confounders and trial effect. Regression analyses were performed to look for effects of covariates on outcomes, and mixed-effects models were used to account for a trial effect. Sensitivity analyses were conducted to explore the effects of missing data and excluding each trial. Results Anterior cruciate ligament reconstruction with patellar tendon autograft was significantly associated with a decreased risk of a positive pivot-shift test result (adjusted odds ratio, 0.46; 95% confidence interval, 0.24–0.86; P = .016). The risk of having a positive Lachman test result was not significantly different between the 2 groups. The estimated treatment effect was not substantially changed by differences in handling missing data or exclusion of any of the trials. A positive pivot-shift test result was more common in female ( P = .003) and younger patients ( P = .017). Conclusion Postoperative knee instability was less common after ACL reconstruction with patellar tendon autograft than with hamstring tendon autograft.
Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice
Authors: Cutts Briony A. , Sjogren Anna-Karin M. , Andersson Karin M. E. , Wahlstrom Annika M. , Karlsson Christin , Swolin Birgitta , Bergo Martin O. 
Published: August 2009

Abstract
Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase–activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS–induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RASG12D in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.
Fatness QTL on chicken chromosome 5 and interaction with sex
Authors: Abasht Behnam , Pitel Frédérique , Lagarrigue Sandrine , Le Bihan-Duval Elisabeth , Le Roy Pascale , Demeure Olivier , Vignoles Florence , Simon Jean , Cogburn Larry , Aggrey Sammy , Vignal Alain , Douaire Madeleine 
Published: August 2009

Abstract
Quantitative trait loci (QTL) affecting fatness in male chickens were previously identified on chromosome 5 (GGA5) in a three-generation design derived from two experimental chicken lines divergently selected for abdominal fat weight. A new design, established from the same pure lines, produced 407 F2 progenies (males and females) from 4 F1-sire families. Body weight and abdominal fat were measured on the F2 at 9 wk of age. In each sire family, selective genotyping was carried out for 48 extreme individuals for abdominal fat using seven microsatellite markers from GGA5. QTL analyses confirmed the presence of QTL for fatness on GGA5 and identified a QTL by sex interaction. By crossing one F1 sire heterozygous at the QTL with lean line dams, three recombinant backcross 1 (BC1) males were produced and their QTL genotypes were assessed in backcross 2 (BC2) progenies. These results confirmed the QTL by sex interaction identified in the F2 generation and they allow mapping of the female QTL to less than 8 Mb at the distal part of the GGA5. They also indicate that fat QTL alleles were segregating in both fat and lean lines.
Comparison of automated candidate gene prediction systems using genes implicated in type 2 diabetes by genome-wide association studies
Authors: Teber Erdahl T , Liu Jason Y , Ballouz Sara , Fatkin Diane , Wouters Merridee A 
Published: August 2009

Abstract

Background
Automated candidate gene prediction systems allow geneticists to hone in on disease genes more rapidly by identifying the most probable candidate genes linked to the disease phenotypes under investigation. Here we assessed the ability of eight different candidate gene prediction systems to predict disease genes in intervals previously associated with type 2 diabetes by benchmarking their performance against genes implicated by recent genome-wide association studies.

Results
Using a search space of 9556 genes, all but one of the systems pruned the genome in favour of genes associated with moderate to highly significant SNPs. Of the 11 genes associated with highly significant SNPs identified by the genome-wide association studies, eight were flagged as likely candidates by at least one of the prediction systems. A list of candidates produced by a previous consensus approach did not match any of the genes implicated by 706 moderate to highly significant SNPs flagged by the genome-wide association studies. We prioritized genes associated with medium significance SNPs.

Conclusion
The study appraises the relative success of several candidate gene prediction systems against independent genetic data. Even when confronted with challengingly large intervals, the candidate gene prediction systems can successfully select likely disease genes. Furthermore, they can be used to filter statistically less-well-supported genetic data to select more likely candidates. We suggest consensus approaches fail because they penalize novel predictions made from independent underlying databases. To realize their full potential further work needs to be done on prioritization and annotation of genes.
CGTS: a site-clustering graph based tagSNP selection algorithm in genotype data
Authors: Wang Jun , Guo Mao-zu , Wang Chun-yu 
Published: August 2009

Abstract

Background
Recent studies have shown genetic variation is the basis of the genome-wide disease association research. However, due to the high cost on genotyping large number of single nucleotide polymorphisms (SNPs), it is essential to choose a small subset of informative SNPs (tagSNPs), which are able to capture most variation in a population, to represent the rest SNPs. Several methods have been proposed to find the minimum set of tagSNPs, but most of them still have some disadvantages such as information loss and block-partition limit.

Results
This paper proposes a new hybrid method named CGTS which combines the ideas of the clustering and the graph algorithms to select tagSNPs on genotype data. This method aims to maximize the number of the discarding nontagSNPs in the given set. CGTS integrates the information of the LD association and the genotype diversity using the site graphs, discards redundant SNPs using the algorithm based on these graph structures. The clustering algorithm is used to reduce the running time of CGTS. The efficiency of the algorithm and quality of solutions are evaluated on biological data and the comparisons with three popular selecting methods are shown in the paper.

Conclusion
Our theoretical analysis and experimental results show that our algorithm CGTS is not only more efficient than other methods but also can be get higher accuracy in tagSNP selection.
Using structural bioinformatics to investigate the impact of non synonymous SNPs and disease mutations: scope and limitations
Authors: Reumers Joke , Schymkowitz Joost , Rousseau Fréderic 
Published: August 2009

Abstract

Background
Linking structural effects of mutations to functional outcomes is a major issue in structural bioinformatics, and many tools and studies have shown that specific structural properties such as stability and residue burial can be used to distinguish neutral variations and disease associated mutations.

Results
We have investigated 39 structural properties on a set of SNPs and disease mutations from the Uniprot Knowledge Base that could be mapped on high quality crystal structures and show that none of these properties can be used as a sole classification criterion to separate the two data sets. Furthermore, we have reviewed the annotation process from mutation to result and identified the liabilities in each step.

Conclusion
Although excellent annotation results of various research groups underline the great potential of using structural bioinformatics to investigate the mechanisms underlying disease, the interpretation of such annotations cannot always be extrapolated to proteome wide variation studies. Difficulties for large-scale studies can be found both on the technical level, i.e. the scarcity of data and the incompleteness of the structural tool suites, and on the conceptual level, i.e. the correct interpretation of the results in a cellular context.
Interleukin-21 induces the differentiation of human umbilical cord blood CD34-lineage- cells into pseudomature lytic NK cells
Authors: Bonanno Giuseppina , Mariotti Andrea , Procoli Annabella , Corallo Maria , Scambia Giovanni , Pierelli Luca , Rutella Sergio 
Published: August 2009

Abstract

Background
Umbilical cord blood (UCB) is enriched with transplantable CD34+ cells. In addition to CD34-expressing haematopoietic stem cells (HSC), human UCB contains a rare population of CD34-lineage- cells endowed with the ability to differentiate along the T/NK pathway in response to interleukin (IL)-15 and a stromal cell support. IL-21 is a crucial regulator of NK cell function, whose influence on IL-15-induced differentiation of CD34-lineage- cells has not been investigated previously. The present study was designed and conducted to address whether IL-21 might replace the stromal cell requirements and foster the IL-15-induced NK differentiation of human UCB CD34-lineage- cells.

Results
CD34-lineage- cells were maintained in liquid culture with Flt3-L and SCF, with the addition of IL-15 and IL-21, either alone or in combination. Cultures were established in the absence of feeder cells or serum supplementation. Cytokine-treated cells were used to evaluate cell surface phenotype, expression of molecular determinants of lymphoid/NK cell differentiation, secretion of IFN-γ, GM-CSF, TNF-α and CCL3/MIP-1α, and cytolytic activity against NK-sensitive tumour cell targets. CD34-lineage- cells proliferated vigorously in response to IL-15 and IL-21 but not to IL-21 alone, and up-regulated phosphorylated Stat1 and Stat3 proteins. CD34-lineage- cells expanded by IL-21 in combination with IL-15 acquired lymphoid morphology and killer-cell immunoglobulin-like receptor (KIR)-CD56+CD16-/+ phenotype, consistent with pseudo-mature NK cells. IL-21/IL-15-differentiated cells expressed high levels of mRNA for Bcl-2, GATA-3 and Id2, a master switch required for NK-cell development, and harboured un-rearranged TCRγ genes. From a functional standpoint, IL-21/IL-15-treated cells secreted copious amounts of IFN-γ, GM-CSF and CCL3/MIP-1α, and expressed cell surface CD107a upon contact with NK-sensitive tumour targets, a measure of exocytosis of NK secretory granules.

Conclusion
This study underpins a novel role for IL-21 in the differentiation of pseudo-mature lytic NK cells in a synergistic context with IL-15, and identifies a potential strategy to expand functional NK cells for immunotherapy.
Extracellular secretion of Carocin S1 in Pectobacterium carotovorum subsp. carotovorumoccurs via the type III secretion system integral to the bacterial flagellum
Authors: Chan Yung-chieh , Wu Huang-Pin , Chuang Duen-yau 
Published: August 2009

Abstract

Background

Pectobacterium carotovorum subsp. carotovorum is a phytopathogenic enterobacterium responsible for soft rot, a disease characterized by extensive maceration of the affected plant tissue. This species also produces two or more antibacterial substances called bacteriocins, which enhance its competitiveness against related rival species. However, the secretion mechanism for low-molecular-weight bacteriocin is still unknown.

Results
A mutant (flhC::Tn5) that did not secrete the low-molecular-weight bacteriocin (LMWB), Carocin S1, was generated by Tn5 insertional mutagenesis. Sequence analysis indicated that this insertion disrupted open reading frame 2 (ORF2) and ORF3 of this strain. Deletion and rescue experiments indicated that ORF2 and ORF3 were both required for extracellular LMWB secretion. The ORF2 and ORF3 sequences showed high homology with the flhD and flhC gene sequences of Pectobacterium carotovorum subsp. atroseptica, Serratia marcescens, Yersinia enterocolitica, and Escherichia coli, indicating that they likely encoded key regulatory components of the type III flagella secretion system.

Conclusion
Thus, the extracellular export of Carocin S1 by Pectobacterium carotovorum subsp. carotovorum appears to utilize the type III secretion system integral to bacterial flagella.
Perceiving pitch absolutely: Comparing absolute and relative pitch possessors in a pitch memory task
Authors: Schulze Katrin , Gaab Nadine , Schlaug Gottfried 
Published: August 2009

Abstract

Background
The perceptual-cognitive mechanisms and neural correlates of Absolute Pitch (AP) are not fully understood. The aim of this fMRI study was to examine the neural network underlying AP using a pitch memory experiment and contrasting two groups of musicians with each other, those that have AP and those that do not.

Results
We found a common activation pattern for both groups that included the superior temporal gyrus (STG) extending into the adjacent superior temporal sulcus (STS), the inferior parietal lobule (IPL) extending into the adjacent intraparietal sulcus (IPS), the posterior part of the inferior frontal gyrus (IFG), the pre-supplementary motor area (pre-SMA), and superior lateral cerebellar regions. Significant between-group differences were seen in the left STS during the early encoding phase of the pitch memory task (more activation in AP musicians) and in the right superior parietal lobule (SPL)/intraparietal sulcus (IPS) during the early perceptual phase (ITP 0–3) and later working memory/multimodal encoding phase of the pitch memory task (more activation in non-AP musicians). Non-significant between-group trends were seen in the posterior IFG (more in AP musicians) and the IPL (more anterior activations in the non-AP group and more posterior activations in the AP group).

Conclusion
Since the increased activation of the left STS in AP musicians was observed during the early perceptual encoding phase and since the STS has been shown to be involved in categorization tasks, its activation might suggest that AP musicians involve categorization regions in tonal tasks. The increased activation of the right SPL/IPS in non-AP musicians indicates either an increased use of regions that are part of a tonal working memory (WM) network, or the use of a multimodal encoding strategy such as the utilization of a visual-spatial mapping scheme (i.e., imagining notes on a staff or using a spatial coding for their relative pitch height) for pitch information.
A mammalianized synthetic nitroreductase gene for high-level expression
Authors: Grohmann Maik , Paulmann Nils , Fleischhauer Sebastian , Vowinckel Jakob , Priller Josef , Walther Diego J 
Published: August 2009

Abstract

Background
The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy.

Methods
We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays.

Results
In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect.

Conclusion
Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans.
Inhibitory effect of IL-8 on insulin action in human adipocytes via MAP kinase pathway
Authors: Kobashi Chikaaki , Asamizu Sachie , Ishiki Manabu , Iwata Minoru , Usui Isao , Yamazaki Katusuya , Tobe Kazuyuki , Kobayashi Masashi , Urakaze Masaharu 
Published: August 2009

Abstract

Background
Various cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue. They might be involved in complications associated with obesity and diabetes. Recently, interleukin-8 (IL-8) has been shown to be produced and released from human adipose tissue and/or adipocytes, suggesting IL-8 involvement in some obesity-related health complications. Therefore, we found it of interest to investigate whether IL-8 is involved in the insulin action in human adipocytes.

Methods
The IL-8 levels in the medium were measured using ELISA. The IL-8 mRNA expression was analyzed using Northern blot analysis. The phosphorylation of Akt was analyzed using Western blot analysis. Furthermore, we examined the effect of IL-8 on the phosphorylation of Akt induced by insulin.

Results
The level of IL-8 in the medium and the IL-8 mRNA expression after stimulation with either TNF-α, IL-1β, or CRP was significantly enhanced in human adipocytes. It is particularly interesting that IL-8 per se also enhanced IL-8 mRNA expression. The IL-8 induced-IL-8 mRNA expression was inhibited by PD98059 (a MEK inhibitor) or SB203580 (a p38 MAPK inhibitor). The IL-8 inhibited insulin-induced Akt phosphorylation. The inhibitory effect of IL-8 was eliminated by either PD 98059 or SB203580.

Conclusion
These data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin-induced Akt phosphorylation in adipocytes. The attenuation of IL-8 action might be a target for prevention of diabetes and its complications.
A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus
Authors: Guilding Clare , Hughes Alun TL , Brown Timothy M , Namvar Sara , Piggins Hugh D 
Published: August 2009

Abstract

Background
In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN) enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc) now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH), a site pivotal for optimal internal homeostatic regulation.

Results
Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc) and dorsomedial nuclei (DMH). Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT). A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT.

Conclusion
Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism.