bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and molecular variability in congenital dyserythropoietic anaemia type I
Authors: Tamary Hannah , Dgany Orly , Proust Alexis , Krasnov Tatyana , Avidan Nili , Eidelitz‐Markus Tal , Tchernia Gil , Geneviève David , Cormier‐Daire Valérie , Bader‐Meunier Brigitte , Ferrero‐Vacher Corinne , Munzer Martine , Gruppo Ralph , Fibach Eithan , Konen Osnat , Yaniv Isaac , Delaunay Jean 
Published: July 2005

SummaryCongenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone disease has only occasionally been associated with this disease. CDA I is caused by mutations in the CDAN1 gene encoding for codanin‐1. Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease. Six novel mutations in the CDAN1 gene were identified. In two patients, one mutation and in another, both mutations were elusive. No patient was homozygous for a null‐type mutation. However, one patient with complex bone disease was homozygous for a splice‐site mutation (IVS‐12+5G > A). Western blotting revealed that codanin‐1 synthesis was 65% less than the control. Five single nucleotide polymorphisms (SNPs) previously unreported in the literature or the SNP database were also identified. Although the absence of codanin‐1 is probably lethal, the presence of 35% of the protein was compatible with life but was associated with severe clinical manifestations. However, in most patients studied, no correlation could be established between the expected levels of codanin‐1 or the nature of the mutation and the severity of the clinical manifestations.
Zoledronate synergises with imatinib mesylate to inhibit Ph+ primary leukaemic cell growth
Authors: Segawa Hidekazu , Kimura Shinya , Kuroda Junya , Sato Kiyoshi , Yokota Asumi , Kawata Eri , Kamitsuji Yuri , Ashihara Eishi , Yuasa Takeshi , Fujiyama Yoshihide , Ottmann Oliver G. , Maekawa Taira 
Published: July 2005

SummaryWe examined the in vivo effects and safety of the third generation bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate against primary Philadelphia chromosome positive (Ph+) leukaemic cells. ZOL inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised with imatinib to enhance the survival of mice engrafted with cells from imatinib‐responders, but not from non‐responders because of mutated BCR‐ABL. These findings suggest that the combination of ZOL and imatinib accelerate the eradication of Ph+ clone, resulting in better prognosis of Ph+ leukaemia patients who have not yet acquired mutations.
Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation
Authors: Kampmann B. , Cubitt D. , Walls T. , Naik P. , Depala M. , Samarasinghe S. , Robson D. , Hassan A. , Rao K. , Gaspar H. , Davies G. , Jones A. , Cale C. , Gilmour K. , Real M. , Foo M. , Bennett‐Rees N. , Hewitt A. , Amrolia P. , Veys Paul 
Published: July 2005

SummaryAdenovirus (AdV) infections are a frequent cause of morbidity and mortality following allogeneic stem cell transplantation (SCT), and disseminated infection is associated with high mortality, particularly in paediatric SCT. Here, we describe an approach to reduce mortality from adenoviraemia by combining prospective monitoring for the occurrence of adenoviraemia using a sensitive polymerase chain reaction method, early antiviral therapy and prompt withdrawal of immunosuppression. A total of 155 consecutive paediatric SCT procedures were prospectively monitored, of which 113 (73%) transplants involved donors other than matched siblings and 126 (83%) employed T‐cell depletion. Adenoviraemia was detected in 26/155 (17%) transplants and developed exclusively in patients who had received T‐cell‐depleted grafts. Withdrawal of immunosuppression coupled with early antiviral therapy led to resolution of adenoviraemia in 19/26 (81%) patients with only five patients succumbing to disseminate AdV infection. Survival from adenoviraemia was associated with lymphocyte recovery to above 0·3 × 109/l. Mortality was closely linked with the absence of lymphocyte recovery because of profound T‐cell depletion of the graft with CD34+ magnetic‐activated cell sorting. Mortality from disseminated AdV infection was 5/26 (19%) in this study, which is significantly lower than previously reported.
Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL‐R1 and TRAIL‐R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin‐ and bortezomib‐induced cell death
Authors: Georgakis Georgios V. , Li Yang , Humphreys Robin , Andreeff Michael , O'Brien Susan , Younes Mamoun , Carbone Antonino , Albert Vivian , Younes Anas 
Published: July 2005

SummaryTumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL/Apo2L) is a death protein that preferentially kills tumour cells while sparing normal cells. TRAIL has four exclusive receptors, two of which (TRAIL‐R1, TRAIL‐R2) are death receptors. Both TRAIL/Apo2L and agonistic antibodies to the TRAIL death receptors are currently being explored for cancer therapy. Although the activity of TRAIL/Apo2L in a variety of haematological malignancies has been examined, the activity of anti‐TRAIL receptor agonistic antibodies in primary and cultured lymphoma cells has not. Using two fully human selective agonistic monoclonal antibodies to the TRAIL death receptors TRAIL‐R1 (HGS‐ETR1) and TRAIL‐R2 (HGS‐ETR2) this study demonstrated that both monoclonal antibodies activated caspase‐8 and induced cell death in five of nine human lymphoma cell lines, and induced >10% cell death in 67% and 70%, respectively, of 27 primary lymphoma cells, and >20% cell death in at least one‐thirds of the samples. HGS‐ETR1 and HGS‐ETR2 demonstrated comparable activity in the fresh tumour samples, which was independent of TRAIL receptor surface expression, Bax, cFLIP, or procaspase‐8 expression, or exposure to prior therapy. Furthermore, both antibodies enhanced the killing effect of doxorubicin and bortezomib. Our data demonstrate that HGS‐ETR1 and HGS‐ETR2 monoclonal antibodies can induce cell death in a variety of cultured and primary lymphoma cells, and may have therapeutic value in lymphoma.
188Re or 90Y‐labelled anti‐CD66 antibody as part of a dose‐reduced conditioning regimen for patients with acute leukaemia or myelodysplastic syndrome over the age of 55: results of a phase I–II study
Authors: Ringhoffer Mark , Blumstein Norbert , Neumaier Bernd , Glatting Gerhard , von Harsdorf Stephanie , Buchmann Inga , Wiesneth Markus , Kotzerke Jörg , Zenz Thorsten , Buck Andreas K. , Schauwecker Peter , Stilgenbauer Stephan , Döhner Hartmut , Reske Sven N. , Bunjes Donald 
Published: July 2005

SummaryIn a phase I–II study for patients aged 55–65 years, we employed radioimmunotherapy using an anti‐CD‐66 antibody as part of a dose‐reduced conditioning regimen, which was followed by a T‐cell‐depleted graft. 20 patients with a median age of 63 years suffering from acute leukaemia (n = 17) or myelodysplastic syndrome (n = 3) received the antibody labelled either with 188Rhenium (n = 8) or with 90Yttrium (n = 12) during conditioning. Radioimmunotherapy provided a mean dose of 21·9 (±8·4) Gy to the bone marrow with a significantly higher dose when 90Yttrium was used. Additional conditioning was fludarabine‐based plus anti‐thymocyte globulin in matched related donor transplants (n = 11), or plus melphalan in matched unrelated donor transplants (n = 9). Regimen‐related toxicity was low, with two patients developing three episodes of grade III organ toxicity. All patients engrafted, grade II–IV acute graft‐versus‐host disease (GvHD) was observed in one patient (5%) and chronic GvHD in three patients (15%). The cumulative incidence of non‐relapse mortality was 25%, the cumulative incidence of relapse 55%. The probability of survival was estimated to be 70% at 1 year and 52% at 2 years post‐transplant, although no plateau was reached afterwards. In conclusion, radioimmunotherapy using the anti‐CD66 antibody was feasible and safe in our elderly patient group and provided a high marrow dose.
Infectious pancreatic necrosis in Atlantic salmon, Salmo salar L.
Authors: Roberts R J , Pearson M D 
Published: July 2005

AbstractA clinical and histopathological review was carried out of 21 outbreaks of acute infectious pancreatic necrosis (IPN) in Scottish Atlantic salmon, Salmo salar L., farms (13 marine and eight fresh water) during 1991–2004. A distinctive syndrome was evident in both post‐smolts in sea water and fry in fresh water, where liver lesions, which had not previously been associated with IPN, became a consistent finding in addition to the more typical pancreatic and intestinal changes. Initial cases were described in post‐smolts in Shetland, but by the end of the period of investigation this type of pathology had extended down the West coast of Scotland and into Ireland. Limited viral strain analysis suggested that similar strains were involved in both fresh water and sea water and that these differed from earlier isolates from rainbow trout, Oncorhynchus mykiss (Walbaum). In fresh water, recovered fish frequently developed a greatly distended intestine associated with accumulation of undigested food. In sea water, after the initial, often significant (50% or more), losses, there were many fish which failed to grow and became chronically emaciated and prone to sea louse infection. Although use of transfer diets containing immune enhancers and the selection of IPN resistant broodstock has reduced losses the disease remains a serious cause of economic loss.
Virulence factors and pathogenicity of Hafnia alvei for gilthead seabream, Sparus aurata L.
Authors: Padilla D , Real F , Gómez V , Sierra E , Acosta B , Déniz S , Acosta F 
Published: July 2005

AbstractVirulence factors (eae gene, haemolytic capacity, fimbriae, resistance to the bactericidal effect of serum, siderophore production) and pathogenicity for gilthead seabream, Sparus aurata L., were analysed for 23 Hafnia alvei strains. None of the strains used in LD50 studies were lethal for seabream at doses as high as >108 cfu mL−1. In chronic challenge studies differences in severity of the inflammatory response were observed between strains. On the basis of correlation of the inflammatory response to different strains of H. alvei in seabream with those virulence factors studied, it was only possible to establish a positive correlation between pathogenicity and resistance to the bactericidal effect of fish serum. Gilthead seabream is thus a species with considerable resistance to experimental infection with H. alvei. The bacterium does, however, have the capacity to remain viable in seabream for up to 3 months, without any clinical signs. Hafnia alvei is a well‐recognized human and animal pathogen. Thus, as the pathogen can coexist with aquaculture operations, cultured gilthead seabream could represent a risk to human health as a carrier in some circumstances.
Identification and structural characterization of an unusual mycobacterial monomeromycolyl‐diacylglycerol
Authors: Kremer Laurent , De Chastellier Chantal , Dobson Gary , Gibson Kevin J. C. , Bifani Pablo , Balor Stéphanie , Gorvel Jean‐Pierre , Locht Camille , Minnikin David E. , Besra Gurdyal S. 
Published: July 2005

SummarySystematic thin layer chromatographic (TLC) analysis of apolar lipids in Mycobacterium kansasii revealed the presence of a previously uncharacterized novel component. The product was ubiquitously found in a panel of M. kansasii clinical isolates, as well as other pathogenic and non‐pathogenic mycobacterial species. TLC analysis of [14C]‐acetate‐ or [14C]‐glycerol‐labelled M. kansasii cultures tentatively assigned the novel product as an unusual triacylglycerol‐related lipid. Subsequent purification, followed by structural determination using 1H‐nuclear magnetic resonance (NMR) and electrospray mass spectrometry (ES/MS), led to the identification of this product as a monomeromycolyl‐diacylglycerol (MMDAG). Treatment of M. kansasii with either isoniazid (INH), a well‐known type II fatty acid synthase (FAS‐II) and mycolic acid biosynthesis inhibitor, or tetrahydrolipstatin (THL), a drug approved for treating obesity, correlated with a reduced incorporation of [14C]‐acetate into both mycolic acids and MMDAG. Addition of INH or THL to the cultures induced major morphological changes and, surprisingly, resulted in an increased number of lipid storage bodies, as determined by electron microscopy. The potent antimycobacterial activity of THL was confirmed against a variety of mycobacterial species, including INH‐susceptible and ‐resistant Mycobacterium tuberculosis strains. Therefore, THL and other β‐lactones may be promising drugs for the development of new antitubercular therapy.
A symbiosis expressed non‐ribosomal peptide synthetase from a mutualistic fungal endophyte of perennial ryegrass confers protection to the symbiotum from insect herbivory
Authors: Tanaka Aiko , Tapper Brian A. , Popay Alison , Parker Emily J. , Scott Barry 
Published: July 2005

SummaryWhile much is known about the biosynthesis of secondary metabolites by filamentous fungi their biological role is often less clear. The assumption is these pathways have adaptive value to the organism but often the evidence to support this role is lacking. We provide the first genetic evidence that the fungal produced secondary metabolite, peramine, protects a host plant from insect herbivory. Peramine is a potent insect feeding deterrent synthesized by Epichloë/Neotyphodium mutualistic endophytes in association with their grass hosts. The structure of peramine, a pyrrolopyrazine, suggests that it is the product of a reaction catalysed by a two‐module non‐ribosomal peptide synthetase (NRPS). Candidate sequences for a peramine synthetase were amplified by reverse transcription polymerase chain reaction. Four unique NRPS products were identified, two of which were preferentially expressed in planta. One of these hybridized to known peramine producing strains. This clone was used to isolate an Epichloë festucae cosmid that contained a two‐module NRPS, designated perA. Nine additional genes, which show striking conservation of microsynteny with Fusarium graminearum and other fungal genomes, were identified on the perA‐containing cosmid. Associations between perennial ryegrass and an E. festucae mutant deleted for perA lack detectable levels of peramine. A wild‐type copy of perA complemented the deletion mutant, confirming that perA is a NRPS required for peramine biosynthesis. In a choice bioassay, plant material containing the perA mutant was as susceptible to Argentine stem weevil (ASW) (Listronotus bonariensis) feeding damage as endophyte‐free plants confirming that peramine is the E. festucae metabolite responsible for ASW feeding deterrent activity.
The crystal structures of Lactococcus lactis MG1363 Dps proteins reveal the presence of an N‐terminal helix that is required for DNA binding
Authors: Stillman Timothy J. , Upadhyay Manisha , Norte Valia A. , Sedelnikova Svetlana E. , Carradus Maria , Tzokov Svetomir , Bullough Per A. , Shearman Claire A. , Gasson Michael J. , Williams Colin H. , Artymiuk Peter J. , Green Jeffrey 
Published: July 2005

SummaryDps proteins play a major role in the protection of bacterial DNA from damage by reactive oxygen species. Previous studies have implicated the extended lysine‐containing N‐terminal regions of Dps subunits in DNA binding, but this part of the structure has not previously been observed crystallographically. Here the structures of two Dps proteins (DpsA and DpsB) from Lactococcus lactis MG1363 reveal for the first time the presence of an N‐terminal α helix that extends from the core of the Dps subunit. Consequently, the N‐terminal helices are displayed in parallel pairs on the exterior of the dodecameric Dps assemblies. Both DpsA and DpsB bind DNA. Deletion of the DpsA N‐terminal helix impaired DNA binding. The N‐terminal Lys residues of Escherichia coli Dps have been implicated in DNA binding. Replacement of the lactococcal DpsA Lys residues 9, 15 and 16 by Glu did not inhibit DNA binding. However, DNA binding was inhibited by EDTA, suggesting a role for cations in DNA binding. In contrast to E. coli, Bacillus brevis and Mycobacterium smegmatis Dps:DNA complexes, in which DNA interacts with crystalline Dps phases, L. lactis DNA:Dps complexes appeared as non‐crystalline aggregates of protein and DNA in electron micrographs.
Modulated targeting of GFP‐AtMAP65‐1 to central spindle microtubules during division
Authors: Mao Guojie , Chan Jordi , Calder Grant , Doonan John H. , Lloyd Clive W. 
Published: July 2005

SummaryAtMAP65‐1 bundles cortical microtubules and we examined how this property is regulated during division in time‐lapse studies of Arabidopsis suspension cells expressing GFP‐AtMAP65‐1. Spindle fluorescence is diffuse during metaphase, restored to the central spindle at anaphase and then compacted at the midline during late anaphase/early telophase. However, mutagenesis of the microtubule‐associated protein (MAP) consensus Cdk site to a non‐phosphorylatable form allows premature decoration of microtubules traversing the central region of the metaphase spindle without affecting the timing of the subsequent compaction. This suggests that mutagenesis does not affect compaction but does affect a phosphorylation/dephosphorylation switch that normally targets AtMAP65‐1 to the central spindle at the metaphase/anaphase transition. GFP‐AtMAP65‐1 continues to label the midline of the early phragmoplast, suggesting a structural continuity with the central spindle – both structures being composed of anti‐parallel microtubules. However, once the cytokinetic apparatus expands into a ring the MAP becomes depleted at the midline. Despite this, cytokinesis is not arrested and membrane and callose are deposited at the cell plate. It is concluded that AtMAP65‐1 plays a role in the central spindle at anaphase to early cytokinesis but is not essential at the midline of the phragmoplast at later stages.
Tiling array‐driven elucidation of transcriptional structures based on maximum‐likelihood and Markov models
Authors: Toyoda Tetsuro , Shinozaki Kazuo 
Published: July 2005

SummaryTiling arrays of high‐density oligonucleotide probes spanning the entire genome are powerful tools for the discovery of new genes. However, it is difficult to determine the structure of the spliced product of a structurally unknown gene from noisy array signals only. Here we introduce a statistical method that estimates the precise splicing points and the exon/intron structure of a structurally unknown gene by maximizing the odds or the ratio of posterior probabilities of the structure under the observation of array signal intensities and nucleic acid sequences. Our method more accurately predicted the gene structures than the simple threshold‐based method, and more correctly estimated the expression values of structurally unknown genes than the window‐based method. It was observed that the Markov model contributed to the precision of splice points, and that the statistical significance of expression (P‐value) represented the reliability of the estimated gene structure and expression value well. We have implemented the method as a program ARTADE (ARabidopsis Tiling Array‐based Detection of Exons) and applied it to the Arabidopsis thaliana whole‐genome array data analysis. The database of the predicted results and the ARTADE program are available at http://omicspace.riken.jp/ARTADE/.
UPF3 suppresses aberrant spliced mRNA in Arabidopsis
Authors: Hori Koichi , Watanabe Yuichiro 
Published: July 2005

SummaryIt has been reported that eukaryotic organisms have a nonsense‐mediated mRNA decay (NMD) system to exclude aberrant mRNAs that produce truncated proteins. NMD is an RNA surveillance pathway that degrades mRNAs possessing premature translation termination codons (PTCs), thus avoiding production of possibly toxic truncated proteins. Three interacting proteins, UPF1, UPF2 and UPF3, are required for NMD in mammals and yeasts, and their amino acid sequences are well conserved among most eukaryotes, including plants. In this study, ‘The Arabidopsis Information Resource’ database was searched for mRNAs with premature termination codons. We selected five of these mRNAs and checked for the presence of PTCs in these mRNAs when translated in vivo. As a result we identified aberrant mRNAs produced by alternative splicing for each gene. These genes produced at least one alternative splicing variant including a PTC (PTC+) and another variant without a PTC (PTC−). We analyzed their PTC+/PTC− ratios in wild‐type Arabidopsis and upf3 mutant plants and showed that the PTC+/PTC− ratios were higher in atupf3 mutant plants than wild‐type plants and that the atupf3 mutant was less able to degrade mRNAs with premature termination codons than wild‐type plants. This indicated that the AtUPF3 gene is required by the plant NMD system to obviate aberrantly spliced mRNA.
Identification, subcellular localization and biochemical characterization of water‐soluble heteroglycans (SHG) in leaves of Arabidopsis thaliana L.: distinct SHG reside in the cytosol and in the apoplast
Authors: Fettke Joerg , Eckermann Nora , Tiessen Axel , Geigenberger Peter , Steup Martin 
Published: July 2005

SummaryWater‐soluble heteroglycans (SHG) were isolated from leaves of wild‐type Arabidopsis thaliana L. and from two starch‐deficient mutants. Major constituents of the SHG are arabinose, galactose, rhamnose, and glucose. SHG was separated into low (<10 kDa; SHGS) and high (>10 kDa; SHGL) molecular weight compounds. SHGS was resolved into approximately 25 distinct oligoglycans by ion exchange chromatography. SHGL was further separated into two subfractions, designated as subfraction I and II, by field flow fractionation. For the intracellular localization of the various SHG compounds several approaches were chosen: first, leaf material was subjected to non‐aqueous fractionation. The apolar gradient fractions were characterized by monitoring markers and were used as starting material for the SHG isolation. Subfraction I and SHGS exhibited a distribution similar to that of cytosolic markers whereas subfraction II cofractionated with crystalline cellulose. Secondly, intact organelles were isolated and used for SHG isolation. Preparations of intact organelles (mitochondria plus peroxisomes) contained no significant amount of any heteroglycan. In isolated intact microsomes a series of oligoglycans was recovered but neither subfraction I nor II. In in vitro assays using glucose 1‐phosphate and recombinant cytosolic (Pho 2) phosphorylase both SHGS and subfraction I acted as glucosyl acceptor whereas subfraction II was essentially inactive. Rabbit muscle phosphorylase a did not utilize any of the plant glycans indicating a specific Pho 2–glycan interaction. As revealed by in vivo labeling experiments using 14CO2 carbon fluxes into subfraction I and II differed. Furthermore, in leaves the pool size of subfraction I varied during the light–dark regime.