bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Nuclear Pore Protein AtTPR Is Required for RNA Homeostasis, Flowering Time, and Auxin Signaling
Authors: Jacob Yannick , Mongkolsiriwatana Chareerat , Veley Kira M. , Kim Sang Yeol , Michaels Scott D. 
Published: May 2007

AbstractNuclear pore complexes (NPCs) mediate the transport of RNA and other cargo between the nucleus and the cytoplasm. In vertebrates, the NPC protein TRANSLOCATED PROMOTER REGION (TPR) is associated with the inner filaments of the nuclear basket and is thought to serve as a scaffold for the assembly of transport machinery. In a screen for mutants that suppress the expression of the floral inhibitor FLOWERING LOCUS C, we identified lesions in the Arabidopsis (Arabidopsis thaliana) homolog of TPR (AtTPR). attpr mutants exhibit early-flowering and other pleiotropic phenotypes. A possible explanation for these developmental defects is that attpr mutants exhibit an approximately 8-fold increase in nuclear polyA RNA. Thus AtTPR is required for the efficient export of RNA from the nucleus. Microarray analysis shows that, in wild type, transcript abundance in the nuclear and total RNA pools are highly correlated; whereas, in attpr mutants, a significantly larger fraction of transcripts is enriched in either the nuclear or total pool. Thus AtTPR is required for homeostasis between nuclear and cytoplasmic RNA. We also show that the effects of AtTPR on small RNA abundance and auxin signaling are similar to that of two other NPC-associated proteins, HASTY (HST) and SUPPRESSOR OF AUXIN RESISTANCE3 (SAR3). This suggests that AtTPR, HST, and SAR3 may play related roles in the function of the nuclear pore.
Physical Association of the NB-LRR Resistance Protein Rx with a Ran GTPase–Activating Protein Is Required for Extreme Resistance toPotato virus X
Authors: Tameling Wladimir I.L. , Baulcombe David C. 
Published: May 2007

AbstractNucleotide binding leucine-rich repeat (NB-LRR) proteins play an important role in plant and mammalian innate immunity. In plants, these resistance proteins recognize specific pathogen-derived effector proteins. Recognition subsequently triggers a rapid and efficient defense response often associated with the hypersensitive response and other poorly understood processes that suppress the pathogen. To investigate mechanisms associated with the activation of disease resistance responses, we investigated proteins binding to the potato (Solanum tuberosum) NB-LRR protein Rx that confers extreme resistance to Potato virus X (PVX) in potato and Nicotiana benthamiana. By affinity purification experiments, we identified an endogenous N. benthamiana Ran GTPase–Activating Protein2 (RanGAP2) as an Rx-associated protein in vivo. Further characterization confirmed the specificity of this interaction and showed that the association occurs through their N-terminal domains. By specific virus-induced gene silencing of RanGAP2 in N. benthamiana carrying Rx, we demonstrated that this interaction is required for extreme resistance to PVX and suggest that RanGAP2 is part of the Rx signaling complex. These results implicate RanGAP-mediated cellular mechanisms, including nucleocytoplasmic trafficking, in the activation of disease resistance.
An SNF2 Protein Associated with Nuclear RNA Silencing and the Spread of a Silencing Signal between Cells inArabidopsis
Authors: Smith Lisa M. , Pontes Olga , Searle Iain , Yelina Nataliya , Yousafzai Faridoon K. , Herr Alan J. , Pikaard Craig S. , Baulcombe David C. 
Published: May 2007

AbstractThe silencing phenotype in Arabidopsis thaliana lines with an inverted repeat transgene under the control of a phloem-specific promoter was manifested in regions around veins due to a mobile signal of silencing. Genetic analysis implicates RNA-DEPENDENT RNA POLYMERASE2 (RDR2) and an RNA polymerase IVa subunit gene (NRPD1a) in the signaling mechanism. We also identified an SNF2 domain–containing protein (CLASSY1) that acts together with RDR2 and NRPD1a in the spread of transgene silencing and in the production of endogenous 24-nucleotide short interfering RNAs (siRNAs). Cytochemical analysis indicates that CLASSY1 may act in the nucleus with NRPD1a and RDR2 in the upstream part of RNA silencing pathways that generate a double-stranded RNA substrate for Dicer-like (DCL) nucleases. DCL3 and ARGONAUTE4 act in a downstream part of the pathway, leading to endogenous 24-nucleotide siRNA production, but are not required for intercellular signaling. From genetic analysis, we conclude that another downstream part of the pathway associated with intercellular signaling requires DCL4 and at least one other protein required for 21-nucleotide trans-acting siRNAs. We interpret the effect of polymerase IVa and trans-acting siRNA pathway mutations in terms of a modular property of RNA silencing pathways.
A familial platelet function disorder associated with abnormal signalling through the glycoprotein VI pathway
Authors: Dunkley Scott , Arthur Jane F. , Evans Sue , Gardiner Elizabeth E. , Shen Yang , Andrews Robert K. 
Published: May 2007

SummaryThe platelet collagen receptor, glycoprotein (GP)VI, of the immunoreceptor family forms a complex with the von Willebrand factor (VWF) receptor, GPIb‐IX‐V, critical for initiating thrombus formation. GPVI is co‐associated with Fc receptor γ‐chain (FcRγ), which contains a cytoplasmic immunoreceptor tyrosine‐based activation motif domain, involved in activation of Syk, and a signalling cascade leading to (i) activation of αIIbβ3, which binds VWF and fibrinogen and mediates platelet aggregation, and (ii) metalloproteinase‐mediated shedding of the GPVI ectodomain (blocked by Syk inhibitors), a key mechanism for regulating GPVI surface expression. In this study, we report a familial case of abnormal platelet aggregation with dysfunctional signalling through GPVI that uniquely demonstrates divergent αIIbβ3‐activating and GPVI‐shedding pathways. The patient is a 60‐year‐old female with a history of immune disorders, excessive bleeding from childhood and a life‐threatening haemorrhage post‐trauma. Platelet aggregation to ADP, thrombin receptor‐agonist peptide or ristocetin/VWF was normal (indicating normal expression and function of αIIbβ3), but platelet aggregation to GPVI agonists, collagen, collagen‐related peptide, or convulxin, was defective. Both GPVI/FcRγ expression and ligand‐induced GPVI ectodomain shedding were normal, confirming expression of functional GPVI/FcRγ, but suggesting a signalling defect downstream of Syk. A genetic defect in GPVI/Fcγ signalling compromising platelet function is hypothesised in this family.
Serum concentrations of angiogenic cytokines in Waldenstrom macroglobulinaemia: the ratio of angiopoietin‐1 to angiopoietin‐2 and angiogenin correlate with disease severity
Authors: Anagnostopoulos Athanasios , Eleftherakis‐Papaiakovou Vangelis , Zervas Konstantinos , Kastritis Efstathios , Tsionos Konstantinos , Bamias Aristotelis , Meletis John , Dimopoulos Meletios A. , Terpos Evangelos 
Published: May 2007

SummaryAngiogenesis represents an essential step of disease progression in several haematological malignancies. Microvessel density is increased in 30% of patients with Waldenstrom macroglobulinaemia (WM), but there is very limited information regarding the role of angiogenic cytokines in this disease. Serum levels of vascular endothelial growth factor (VEGF), VEGF‐A, angiogenin, angiopoietin (Ang)‐1 and ‐2, and basic fibroblast growth factor (bFGF) were evaluated in 56 WM patients at different disease phases (24 untreated, 20 relapsed/refractory and 12 patients at remission) and 11 patients with immunoglobulin M type monoclonal gammopathy of undetermined significance (IgM‐MGUS). All patients had increased levels of angiogenin, VEGF, VEGF‐A, and bFGF compared with controls. The Ang‐1/Ang‐2 ratio was reduced in WM but not in IgM‐MGUS patients. Angiogenin levels correlated with disease status: when compared with healthy subjects, patients with IgM‐MGUS and untreated WM patients had increased angiogenin serum levels, which were higher in untreated WM patients than in MGUS. WM patients at remission had lower angiogenin serum levels compared with untreated patients, but these levels were increased again in active disease post‐therapy. Angiogenin also correlated with albumin levels, while VEGF‐A correlated with β2‐microglobulin (β2M). Ang‐1/Ang‐2 ratio showed a strong, negative correlation with β2M, and positive correlation with albumin, haemoglobin and lymphadenopathy. Our results indicate a potential use of angiogenin levels for follow‐up in WM and angiogenic molecules as targets for the development of novel anti‐WM agents.
Recent advances into the understanding of mesenchymal stem cell trafficking
Authors: Fox James M. , Chamberlain Giselle , Ashton Brian A. , Middleton Jim 
Published: May 2007

SummaryThe use of adult stem cells to regenerate damaged tissue circumvents the moral and technical issues associated with the use of those from an embryonic source. Mesenchymal stem cells (MSC) can be isolated from a variety of tissues, most commonly from the bone marrow, and, although they represent a very small percentage of these cells, are easily expandable. Recently, the use of MSC has provided clinical benefit to patients with osteogenesis imperfecta, graft‐versus‐host disease and myocardial infarction. The cellular cues that enabled the MSC to be directed to the sites of tissue damage and the mechanisms by which MSC then exert their therapeutic effect are becoming clearer. This review discusses the relative therapeutic importance of the ability of MSC to differentiate into multiple cell lineages or stimulate resident or attracted cells via a paracrine mode of action. It also reviews recent findings that MSC home to damaged tissues in a similar, but somewhat distinct, manner to that of leucocytes via the utilisation of adhesion molecules, such as selectins and integrins, and chemokines and their receptors in a manner reminiscent of leucocytes trafficking from the blood stream to inflammatory sites.
MicroRNAs and haematology: small molecules, big function
Authors: Lawrie Charles H. 
Published: May 2007

SummaryMicroRNAs are a recently discovered class of small (∼22nt) endogenously expressed translational‐repressor RNAs that play key roles in many cellular pathways and whose aberrant expression appears to be a common feature of malignancy. MicroRNAs are expressed in specific haematological cell types and play important regulatory roles in early haematopoietic differentiation, erythropoiesis, granulocytosis, megakaryocytosis and lymphoid development. Additionally, there is an emerging body of research to suggest that microRNAs play an important role in the pathology of haematological malignancies. MicroRNAs have been found to act as both tumour suppressor molecules [e.g. MIRN15A (miR‐15a), MIRN16‐1 (miR‐16‐1)] in leukaemias and have oncogenic properties [e.g. MIRN155 (miR‐155) and MIRN17–92 (miR‐17–miR‐92) cluster] in lymphomas. This review discusses the rapidly accumulating research that points to the major role microRNAs play in both haematopoiesis and haematological malignancy.
Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients
Authors: Guazzi M. , Tumminello G. , Reina G. , Vicenzi M. , Guazzi M. D. 
Published: May 2007

AbstractBackground  Statins represent a modern mainstay of the drug treatment of coronary artery disease and acute coronary syndromes. Reduced aerobic work performance and slowed VO2 kinetics are established features of the clinical picture of post‐myocardial infarction (MI) patients. We tested the hypothesis that statin therapy improves VO2 exercise performance in normocholesterolaemic post‐MI patients.Materials and methods  According to a double‐blinded, randomized, crossover and placebo‐controlled study design, in 18 patients with uncomplicated recent (3 days) MI we investigated the effects of atorvastatin (20 mg day−1) on gas exchange kinetics by calculating VO2 effective time constant (tau) during a 50‐watt constant workload exercise, brachial artery flow‐mediated dilatation (FMD) as an index of endothelial function, left ventricular function (echocardiography) and C‐reactive protein (CRP, as an index of inflammation). Atorvastatin or placebo was given for 3 months each.Results  Atorvastatin therapy significantly improved exercise VO2 tau and FMD, and reduced CRP levels. We did not observe changes in cardiac contractile function and relaxation properties during all study periods in either group.Conclusions  In post‐MI patients exercise performance is a potential additional target of benefits related to statin therapy. Endothelial function improvement is very likely implicated in this newly described therapeutic property.
Associations between VHL genotype and clinical phenotype in familial von Hippel–Lindau disease
Authors: Huang J. S. , Huang C. J. , Chen S. K. , Chien C. C. , Chen C. W. , Lin C. M. 
Published: May 2007

AbstractBackground  Von Hippel–Lindau (VHL) disease is an autosomal dominant hereditary disorder associated with tumours and cysts in the central nervous system (CNS) and other visceral organs. Germline mutations in the VHL gene on chromosome 3p25–26 are considered the cause of this disease.Materials and methods  We studied six patients with VHL disease and their relatives. Loss of heterozygosity (LOH) was determined by five flanking microsatellite polymorphic markers in the VHL locus. Multiplex ligation‐dependent probe amplification (MLPA) and quantitative real‐time polymerase chain reaction (qPCR) amplification were used to detect the genomic deletions. Single‐strand conformation polymorphism (SSCP) analysis was applied to test for sequence variations.Results  Three germline deletions in the VHL gene (142·9, 53·3 and 3·3 kb) were found by MLPA. These deletions were defined clearly by qPCR analyses. The142·9 kb germline deletion was significantly associated with patients with CNS haemangioblastomas (P < 0·01 by Fisher's exact test), and one missense mutation (Gln209Arg) was detected from a patient with a pancreatic cyst in the same family. LOH was also detected from a patient with bilateral renal cell carcinomas.Conclusion  Diverse genetic conditions are associated with the clinical manifestations of VHL disease. Genomic deletions that can be detected by MLPA or qPCR are major causes for this syndrome. Missense mutations and LOH accompanying the disease lead to complex clinical symptoms and genotypic determination can facilitate a clinical diagnosis because of their strong association.
Standards and standardization in mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria
Authors: Valent P. , Akin C. , Escribano L. , Födinger M. , Hartmann K. , Brockow K. , Castells M. , Sperr W. R. , Kluin‐Nelemans H. C. , Hamdy N. A. T. , Lortholary O. , Robyn J. , Van Doormaal J. , Sotlar K. , Hauswirth A. W. , Arock M. , Hermine O. , Hellmann A. , Triggiani M. , Niedoszytko M. , Schwartz L. B. , Orfao A. , Horny H.‐P. , Metcalfe D. D. 
Published: May 2007

AbstractAlthough a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease‐specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials.
Age‐related changes in bile acid synthesis and hepatic nuclear receptor expression
Authors: Bertolotti M. , Gabbi C. , Anzivino C. , Crestani M. , Mitro N. , Del Puppo M. , Godio C. , De Fabiani E. , Macchioni D. , Carulli L. , Rossi A. , Ricchi M. , Loria P. , Carulli N. 
Published: May 2007

AbstractBackground  Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7α‐hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7α‐hydroxylase and related nuclear receptor expression in human livers.Design  Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7α‐hydroxylase and related nuclear receptors and co‐activators were assayed by quantitative real‐time RT‐PCR. Serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one, a marker of bile acid synthesis, were assayed by gas‐liquid chromatography:mass spectrometry.Results  Ageing was inversely correlated with serum 7α‐hydroxy‐4‐cholesten‐3‐one and with cholesterol 7α‐hydroxylase mRNA levels (r = –0·44 and r = −0·45 on a semi‐log scale, respectively, P < 0·05). Among different nuclear factors, cholesterol 7α‐hydroxylase mRNA best correlated with hepatocyte nuclear factor‐4 (r = 0·55 on a log scale, P < 0·05); hepatocyte nuclear factor‐4 levels were also inversely correlated with age (r = –0·64 on a semi‐log scale, P < 0·05). Age was inversely correlated with serum insulin‐like growth factor‐I levels, which were directly correlated with hepatocyte nuclear factor‐4 and cholesterol 7α‐hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7α‐hydroxylase was observed.Conclusions  Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor‐4 and consequently of cholesterol 7α‐hydroxylase. Age‐related modifications of the growth hormone/insulin‐like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age‐related modifications of cholesterol metabolism.
Natriuretic peptides and myocardial oxygen supply‐to‐demand ratio in patients with aortic stenosis
Authors: Wagner J. A. , Störk S. , Weidemann F. , Strotmann J. , Fiedel C. , Ertl G. , Voelker W. 
Published: May 2007

AbstractBackground  In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino‐terminal pro‐hormone (NT‐proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT‐proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS.Design  In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply‐to‐demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross‐sectionally assessed.Results  Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS (n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status (P = 0·01). BNP and NT‐proBNP values correlated negatively with DPTI/SPTI (r = −0·58 and −0·51, P < 0·001, respectively) and left ventricular (LV) ejection fraction (EF) (r = −0·52 and −0·59, P < 0·001, respectively). DPTI/SPTI correlated with aortic valve area (P < 0·0001) but not with EF. Receiver operating characteristic analysis determined cut‐off values of > 450 pg mL−1 for BNP and of > 1800 pg mL−1 for NT‐proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0·22) in combination with impaired LV systolic function (i.e. EF < 45%).Conclusions  Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement.
The hepatic lipase gene C‐480T polymorphism in the development of early coronary atherosclerosis: the Helsinki Sudden Death Study
Authors: Fan Y. M. , Lehtimäki T. , Rontu R. , Ilveskoski E. , Goebeler S. , Kajander O. , Mikkelsson J. , Viiri L. E. , Perola M. , Karhunen P. J. 
Published: May 2007

AbstractBackground  The T allele of the hepatic lipase (HL) C‐480T polymorphism was previously found to be associated with lower post‐heparin plasma HL activity, atherosclerosis and risk of coronary artery disease. We studied the association of HL C‐480T polymorphism with the extent of atherosclerosis at vessel‐wall level in an autopsy series of middle‐aged men.Materials and methods  An autopsy cohort of 700 Caucasian Finnish men aged 33–70 years (mean 53 years), which comprised two autopsy series, collected 10 years apart during 1981–82 and 1991–92, were analysed. Areas of coronary wall covered with fatty streaks and fibrotic and complicated lesions were measured using computer‐assisted planimetry and related to HL C‐480T genotypes (CC, CT, and TT).Results  There was a significant age–by–genotype interaction on the mean percentage area of fatty streaks (P = 0·01). The HL C‐480T polymorphism was a significant explanatory factor for fatty streak area in men under 53 years of age with or without age, body mass index, hypertension, diabetes, smoking, alcohol consumption, apolipoprotein E genotype, and series number as covariates. Men carrying the TT genotype had two times larger areas of fatty streaks compared to the CC carriers (8·8% vs. 4·3%, P = 0·009). However, this association disappeared in men over 53 years. The areas of more advanced atherosclerotic lesions did not vary significantly among the genotype groups.Conclusions  Our results suggest that the HL C‐480T polymorphism affects the formation of early coronary atherosclerotic lesions in men in their early middle age.
Angiotensin‐converting enzyme gene polymorphism and stroke in type 2 diabetic patients in Taiwan
Authors: Tseng C. H. , Tseng C. P. , Chong C. K. , Sheu J. J. , Cheng J. C. 
Published: May 2007

AbstractBackground  The effect of traditional risk factors on the association between angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients.Materials and methods  A total of 872 (422 men and 450 women) patients aged 63·5 (SD: 11·6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes.Results  The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0·837 (0·413–1·697) and 1·778 (0·596–5·300), respectively, for men; but were 1·700 (0·824–3·505) and 3·706 (1·375–9·985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2·784 (1·137–6·818), 1·996 (1·006–3·962) and 1·877 (1·155–3·050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men.Conclusion  Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.