bluuebunny/crossref_metadata_2025_split huggingface dataset:
ND3 and ND4L Subunits of Mitochondrial Complex I, Both Nucleus Encoded in
Chlamydomonas reinhardtii
, Are Required for Activity and Assembly of the Enzyme
Authors: Cardol Pierre , Lapaille Marie , Minet Pierre , Franck Fabrice , Matagne René F. , Remacle Claire 
Published: September 2006

ABSTRACT

Made of more than 40 subunits, the rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) is the most intricate membrane-bound enzyme of the mitochondrial respiratory chain. In vascular plants, fungi, and animals, at least seven complex I subunits (ND1, -2, -3, -4, -4L, -5, and -6; ND is NADH dehydrogenase) are coded by mitochondrial genes. The role of these highly hydrophobic subunits in the enzyme activity and assembly is still poorly understood. In the unicellular green alga
Chlamydomonas reinhardtii
, the ND3 and ND4L subunits are encoded in the nuclear genome, and we show here that the corresponding genes, called
NUO3
and
NUO11
, respectively, display features that facilitate their expression and allow the proper import of the corresponding proteins into mitochondria. In particular, both polypeptides show lower hydrophobicity compared to their mitochondrion-encoded counterparts. The expression of the
NUO3
and
NUO11
genes has been suppressed by RNA interference. We demonstrate that the absence of ND3 or ND4L polypeptides prevents the assembly of the 950-kDa whole complex I and suppresses the enzyme activity. The putative role of hydrophobic ND subunits is discussed in relation to the structure of the complex I enzyme. A model for the assembly pathway of the
Chlamydomonas
enzyme is proposed.
Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase
Authors: Obermann Ellen C , Went Philip , Tzankov Alexandar , Pileri Stefano A , Hofstaedter Ferdinand , Marienhagen Joerg , Stoehr Robert , Dirnhofer Stephan 
Published: September 2006

Background and Aims:Chronic lymphocytic leukaemia (CLL) is a frequent non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of cell cycle phase kinetics might be important for prediction of clinical behaviour and prognosis.Methods:Distribution of neoplastic cells in CLL within the cell cycle was evaluated by determining the labelling indices (LI, i.e. percentage of positive cells) of markers specific for late G1-phase (cyclin E), S-phase (cyclin A), and G2/M-phase (cyclin B1), and Mcm2, a novel marker of proliferative potential, in a large cohort of patients (n = 79) using tissue microarray (TMA) technology. Utilising a combination of these markers, an algorithm was developed—subtracting the combined LIs of cyclin E, cyclin A and cyclin B1 from the LI of Mcm2—to determine the percentage of tumour cells residing in early G1-phase, which is probably a critical state for the malignant potential of CLL.Results:27.11% of cells had acquired proliferative potential as indicated by expression of Mcm2. Only a small number of cells were found to be in late G1-phase (7.16%), S-phase (3.31%) or G2/M-phase (0.98%), while 15.66% of cells were considered to be in early G1-phase.Conclusion:Cell cycle phase distribution can easily be assessed by immunohistochemistry in routinely processed paraffin-embedded specimens. A large number of neoplastic cells in CLL have proliferative potential, with a significant sub-population residing in early G1-phase. Estimates of these cells may identify cases likely to exhibit a more aggressive biological behaviour and adverse clinical course.
A METHOD TO CONSTRUCT FLAT MAPS OF THE BRAIN'S SURFACE AND ITS APPLICATION
Authors: DEKLERCK RUDI , GUO JUNFENG , SALOMIE ALEXANDRU , SULIGA MAREK , NYSSEN EDGARD , TAO LIU , BALERIAUX DANIELLE , CORNELIS JAN 
Published: September 2006

This paper describes a surface flattening technique, which has been developed in particular to obtain a complete view of the cortical surface of the brain. However, the method is able to produce an overall planar view of any anatomical or real-life object, provided it is topologically compatible with the sphere (i.e. genus 0). It computes the shading of the original surface for rays casted from a nearby surrounding surface and unfolds this surface in a 2D plane, without introducing major distortions. The flat image consisting of the mapped shading results has the advantage that the sulci (i.e. the grooves characterizing the superficial brain geometry) of the cortical surface of the brain can be followed in their entirety, which facilitates the study and the recognition of their patterns. The new visualization method is integrated into a versatile medical image analysis environment. A first study to assess its usefulness has been accomplished and is also reported in this paper.
Nonendothelial Mesenchymal Cell–Derived MCP-1 Is Required for FGF-2–Mediated Therapeutic Neovascularization
Authors: Fujii Takaaki , Yonemitsu Yoshikazu , Onimaru Mitsuho , Tanii Mitsugu , Nakano Toshiaki , Egashira Kensuke , Takehara Takako , Inoue Makoto , Hasegawa Mamoru , Kuwano Hiroyuki , Sueishi Katsuo 
Published: September 2006

Objective—Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that is known as an inflammatory/arteriogenic factor. Angiogenesis contributes to the inflammatory process; however, the molecular and cellular mechanisms of the links among the inflammatory pathway, arteriogenesis, and angiogenesis have not been well elucidated.Methods and Results—Using murine models of fibroblast growth factor-2 (FGF-2)–mediated therapeutic neovascularization, we here show that FGF-2 targets nonendothelial mesenchymal cells (NEMCs) enhancing both angiogenic (vascular endothelial growth factor [VEGF]) and arteriogenic (MCP-1) signals via independent signal transduction pathways. Severe hindlimb ischemia stimulated MCP-1 expression that was strongly enhanced by FGF-2 gene transfer, and a blockade of MCP-1 activity via a dominant negative mutant as well as a deficiency of its functional receptor CCR2 resulted in the diminished recovery of blood flow attributable to adaptive and therapeutic neovascularization. Tumor necrosis factor (TNF)-α stimulated MCP-1 expression in all cell types tested, whereas FGF-2–mediated upregulation of MCP-1 was found only in NEMCs but not in others, a finding that was not affected by VEGF in vitro and in vivo.Conclusions—These results indicate that FGF-2 targets NEMCs independently, enhancing both angiogenic (VEGF) as well as inflammatory/arteriogenic (MCP-1) pathways. Therefore, MCP-1/CCR2 plays a critical role in adaptive and FGF-2–mediated therapeutic neovascularization.
Pietro Della Valle's Latin Geography of Safavid Iran (1624-1628): Introduction
Authors: Schüller Volkmar , Brentjes Sonja 
Published: September 2006

AbstractThis article argues that Pietro della Valle's Latin geography of the Safavid Empire is important for taking a middle ground between two common tendencies of early modern authors in Catholic and Protestant Europe when writing about Western Asia and Northern Africa. While cartographers and mapmakers—in Venice, Antwerp, Amsterdam, and Paris—privileged new information (from travelers) in their choice of place names, those who wrote on the history or geography of these regions often suppressed local knowledge, giving preference to terms from ancient Greek and Latin history and geography, enriched by reference to the Bible. Della Valle, while traveling in Ottoman and Safavid territories, made intensive efforts to learn major local languages and acquire information about contemporary political, cultural, and physical geography, as documented in his diary and the original copies of his letters written during the long years of travel. The approach he takes in his geography of the Safavid Empire is thus close to choices made by the cartographers and mapmakers.
Phospholipase C, calcium, and calmodulin are critical for α4β1 integrin affinity up-regulation and monocyte arrest triggered by chemoattractants
Authors: Hyduk Sharon J. , Chan, Jason R. , Duffy Stewart T. , Chen Mian , Peterson Mark D. , Waddell Thomas K. , Digby Genevieve C. , Szaszi Katalin , Kapus Andras , Cybulsky Myron I. 
Published: September 2006

AbstractDuring inflammation, monocytes roll on activated endothelium and arrest after stimulation by proteoglycan-bound chemokines and other chemoattractants. We investigated signaling pathways downstream of G protein–coupled receptors (GPCRs) that are relevant to α4β1 integrin affinity up-regulation using formyl peptide receptor-transfected U937 cells stimulated with fMLP or stromal-derived factor-1α and human peripheral blood monocytes stimulated with multiple chemokines or chemoattractants. The up-regulation of soluble LDV peptide or vascular cell adhesion molecule-1 (VCAM-1) binding by these stimuli was critically dependent on activation of phospholipase C (PLC), inositol 1,4,5-triphosphate receptors, increased intracellular calcium, influx of extracellular calcium, and calmodulin, suggesting that this signaling pathway is required for α4 integrins to assume a high-affinity conformation. In fact, a rise in intracellular calcium following treatment with thapsigargin or ionomycin was sufficient to induce binding of ligand. Blockade of p44/42 and p38 mitogen-activated protein (MAP) kinases, phosphoinositide 3-kinase, or protein kinase C (PKC) signaling did not inhibit chemoattractant-induced LDV or VCAM-1 binding. However, activation of PKC by phorbol ester up-regulated α4β1 affinity with kinetics distinct from those of GPCR signaling. A critical role for PLC and calmodulin was also established for leukocyte arrest and adhesion strengthening.
Durable responses to imatinib in patients with PDGFRB fusion gene–positive and BCR-ABL–negative chronic myeloproliferative disorders
Authors: David Marianna , Cross Nicholas C. P. , Burgstaller Sonja , Chase Andrew , Curtis Claire , Dang Raymond , Gardembas Martine , Goldman John M. , Grand Francis , Hughes George , Huguet Francoise , Lavender Louise , McArthur Grant A. , Mahon Francois X. , Massimini Giorgio , Melo Junia , Rousselot Philippe , Russell-Jones Robin J. , Seymour John F. , Smith Graeme , Stark Alastair , Waghorn Katherine , Nikolova Zariana , Apperley Jane F. 
Published: September 2006

Abstract
Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL–negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL–negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase–polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion–positive, BCR-ABL–negative CMPDs.
Detection of divergent genes in microbial aCGH experiments
Authors: Snipen Lars , Repsilber Dirk , Nyquist Ludvig , Ziegler Andreas , Aakra Ågot , Aastveit Are 
Published: September 2006

Abstract

Background
Array-based comparative genome hybridization (aCGH) is a tool for rapid comparison of genomes from different bacterial strains. The purpose of such analysis is to detect highly divergent or absent genes in a sample strain compared to an index strain. Development of methods for analyzing aCGH data has primarily focused on copy number abberations in cancer research. In microbial aCGH analyses, genes are typically ranked by log-ratios, and classification into divergent or present is done by choosing a cutoff log-ratio, either manually or by statistics calculated from the log-ratio distribution. As experimental settings vary considerably, it is not possible to develop a classical discriminant or statistical learning approach.

Methods
We introduce a more efficient method for analyzing microbial aCGH data using a finite mixture model and a data rotation scheme. Using the average posterior probabilities from the model fitted to log-ratios before and after rotation, we get a score for each gene, and demonstrate its advantages for ranking and detecting divergent genes with enlarged specificity and sensitivity.

Results
The procedure is tested and compared to other approaches on simulated data sets, as well as on four experimental validation data sets for aCGH analysis on fully sequenced strains of Staphylococcus aureus and Streptococcus pneumoniae.

Conclusion
When tested on simulated data as well as on four different experimental validation data sets from experiments with only fully sequenced strains, our procedure out-competes the standard procedures of using a simple log-ratio cutoff for classification into present and divergent genes.
Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements
Authors: Tharakaraman Kannan , Mariño-Ramírez Leonardo , Sheetlin Sergey L , Landsman David , Spouge John L 
Published: September 2006

Abstract

Background
Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set.

Results
We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence.

Conclusion
Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances.
Phase distribution of spliceosomal introns: implications for intron origin
Authors: Nguyen Hung D , Yoshihama Maki , Kenmochi Naoya 
Published: September 2006

Abstract

Background
The origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions.

Results
In this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well.

Conclusion
Our results strongly support the introns-late hypothesis of the origin of spliceosomal introns.
Development of a Premature Stop Codon-detection method based on a bacterial two-hybrid system
Authors: Real Sebastián M , Marzese Diego M , Gomez Laura C , Mayorga Luis S , Roqué María 
Published: September 2006

Abstract

Background
The detection of Premature Stop Codons (PSCs) in human genes is very useful for the genetic diagnosis of different hereditary cancers, e.g. Familial Breast Cancer and Hereditary Non-Polyposis Colorectal Cancer (HNPCC). The products of these PSCs are truncated proteins, detectable in vitro by the Protein Truncation Test and in vivo by using the living translation machinery of yeast or bacteria. These living strategies are based on the construction of recombinant plasmids where the human sequence of interest is inserted upstream of a reporter gene. Although simple, these assays have their limitations. The yeast system requires extensive work to enhance its specificity, and the bacterial systems yield many false results due to translation re-initiation events occurring post PSCs. Our aim was to design a recombinant plasmid useful for detecting PSCs in human genes and resistant to bacterial translation re-initiation interferences.

Results
A functional recombinant plasmid (pREAL) was designed based on a bacterial two-hybrid system. In our design, the in vivo translation of fused fragments of the Bordetella pertussis adenylate cyclase triggers the production of cAMP giving rise to a selectable bacterial phenotype. When a gene of interest is inserted between the two fragments, any PSC inhibits the enzymatic activity of the product, and translation re-initiation events post-PSC yield separated inactive fragments. We demonstrated that the system can accurately detect PSCs in human genes by inserting mutated fragments of the brca1 and msh2 gene. Western Blot assays revealed translation re-initiation events in all the tested colonies, implying that a simpler plasmid would not be resistant to this source of false negative results. The application of the system to a HNPCC family with a nonsense mutation in the msh2 gene correctly diagnosed wild type homozygous and heterozygous patients.

Conclusion
The developed pREAL is applicable to the detection of PSCs in human genes related to different diseases and is resistant to translation re-initiation events. The diagnosis steps are easy, have a low cost, detect only pathologic mutations, and allow the analysis of separated alleles.
Severe osteomyelitis caused by Myceliophthora thermophila after a pitchfork injury
Authors: Destino Lauren , Sutton Deanna A , Helon Anna L , Havens Peter L , Thometz John G , Willoughby Rodney E , Chusid Michael J 
Published: September 2006

Abstract

Background
Traumatic injuries occurring in agricultural settings are often associated with infections caused by unusual organisms. Such agents may be difficult to isolate, identify, and treat effectively.

Case report
A 4-year-old boy developed an extensive infection of his knee and distal femur following a barnyard pitchfork injury. Ultimately the primary infecting agent was determined to be Myceliophthora thermophila, a thermophilic melanized hyphomycete, rarely associated with human infection, found in animal excreta. Because of resistance to standard antifungal agents including amphotericin B and caspofungin, therapy was instituted with a prolonged course of terbinafine and voriconazole. Voriconazole blood levels demonstrated that the patient required a drug dosage (13.4 mg/kg) several fold greater than that recommended for adults in order to attain therapeutic blood levels.

Conclusion
Unusual pathogens should be sought following traumatic farm injuries. Pharmacokinetic studies may be of critical importance when utilizing antifungal therapy with agents for which little information exists regarding drug metabolism in children.
Development of the Well-being questionnaire short-form in Japanese: the W-BQ12
Authors: Riazi Afsane , Bradley Clare , Barendse Shalleen , Ishii Hitoshi 
Published: September 2006

Abstract

Background
The Well-being Questionnaire (W-BQ) was designed to measure psychological well-being in people with diabetes. This study aimed to develop a Japanese version and a short form of the W-BQ.

Methods
A linguistic validation process produced a preliminary Japanese version of the 22-item W-BQ, which was distributed to 550 patients. Factor structure, reliability (Cronbach's alpha) and aspects of validity (hypothesised group differences and correlations with other measures) were evaluated.

Results
Questionnaires were returned by 464 patients (84.4%). Preliminary factor analysis revealed that the Depression and Anxiety items were dispersed according to the positive or negative direction of the wording. A 12-item W-BQ (Japanese W-BQ12), consisting of three 4-item subscales (Negative Well-being, Energy and Positive Well-being), was constructed that balanced positively and negatively worded items. Cronbach's alpha was high (>0.85) for the 12-item questionnaire and consistently high (>0.82) across sex and treatment subgroups. Cronbach's alpha for subscale scores in the total sample ranged from 0.69 (Energy) to 0.80 (Positive Well-being). Expected subgroup differences indicated significantly poorer well-being in women compared with men and in insulin-treated patients compared with tablet/diet treated patients. Discriminant and convergent validity was supported by minimal correlations between W-BQ12 scores and HbA1c and low-to-moderate correlations with Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores.

Conclusion
The W-BQ12 (Japanese) is a short, reliable and valid measure of psychological well-being that is suitable for use with people with diabetes. The items selected to produce the W-BQ12 (Japanese) have since produced psychometrically sound 12-item short-form measures in other translations for use in diabetes and in other chronic illnesses.