bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter hyperintensities on T2-weighted MRI images among DNA-verified older familial hypercholesterolemia patients
Authors: Hyttinen L. , Autti T. , Rauma S. , Soljanlahti S. , Vuorio A. F. , Strandberg T. E. 
Published: February 2009

Background: Familial hypercholesterolemia (FH) is a genetic disorder, causing an increased risk of coronary heart disease (CHD) if untreated. Silent brain infarctions and white matter hyperintensities (WMHIs) observed on T2-weighted magnetic resonance images (MRI) are associated with increased risk for stroke and myocardial infarction. Age is a strong predictor of WMHIs. Purpose: To use MRI to assess the presence of clinically silent brain lesions in older FH patients, and to compare the occurrence and size of these lesions in older FH patients with middle-aged FH patients and healthy controls. Material and Methods: A total of 43 older (age ≥ 65 years) FH patients with the same FH North Karelia mutation, living in Finland, were identified. In this comprehensive cohort, 1.5T brain MRI was available for 33 individuals (age 65–84 years, M/F 9/24, mean duration of statin treatment 15.3 years). This group was divided into two age categories: 65–74 years (FHe1 group, n=23) and 75–84 years (FHe2 group, n=10). Infarcts, including lacunas, and WMHIs on T2-weighted images were recorded. Data from brain MRI were compared to those of a group of middle-aged FH patients with CHD ( n=19, age 48–64 years) and with middle-aged healthy controls ( n=29, age 49–63 years). Results: Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI. The amount of large WMHIs (>5 mm in diameter) was similar in the FHe1 group compared with the groups of middle-aged FH patients and healthy controls, even though the FHe1 group was 13 years older. The total amount of WMHIs and the amount of large WMHIs were greatest in the FHe2 group. Conclusion: FH patients aged 65 to 74 years receiving long-term statin treatment (15 years) did not have more WMHIs on brain MRI compared to middle-aged FH patients and healthy controls.
Incidence and predictors of hospitalization or death in patients managed in multidisciplinary heart failure clinics
Authors: Gustafsson Finn , Schou Morten , Videbæk Lars , Dridi Nadia , Ryde Henrik , Handberg Jens , Hildebrandt Per R. ,   on behalf of the Danish Heart Failure Clinics Network
Published: February 2009

AimsTo assess the rates of death or hospitalization in outpatients with heart failure (HF) followed in multidisciplinary, nurse‐based HF clinics and to compare the rates with published data from the literature. A second aim was to identify risk factors for death or hospital admission.Methods and resultsA total of 4012 consecutive outpatients referred for HF management in 18 Danish HF clinics were included. Clinical data were collected prospectively. Outcome data were obtained from a validated, national registry. Mean follow‐up time was 580 days. The mean age of patients was 69 years, 83% had left ventricular systolic dysfunction and 52% had been hospitalized within 90 days prior to referral to the HF clinic. The 6 and 12 month rates of hospitalization or death were 31 and 42%. Hospitalization or death was significantly predicted by age 1.12 (1.05–1.19), diabetes 1.21 (1.03–1.42), serum creatinine 1.03 (1.02–1.04), NYHA III and IV 1.32 (1.15–1.52), and hospitalization prior to referral to the HF clinic 1.81 (1.57–2.08).ConclusionsEvent rates in this cohort were lower than most published data from HF clinic populations. Factors such as advanced age, NYHA class, and prior hospitalization predict poor outcome in patients managed in multidisciplinary HF clinics.
Long-term evaluation of scientific-echosounder performance
Authors: Knudsen Hans Petter 
Published: February 2009

Abstract
Knudsen, H. P. 2009. Long-term evaluation of scientific-echosounder performance. – ICES Journal of Marine Science, 66: 1335–1340. When scientific acoustic instruments are utilized for quantitative measurements of underwater biological resources, it is extremely important to know their overall performance, and it is imperative to measure their stability over time. Echosounders mounted on research vessels are therefore routinely calibrated several times annually, often immediately before, during, and after important resource-assessment surveys. In recent years, multifrequency systems for acoustic surveys requiring species identification and categorization based on the frequency response of targets have been introduced, further emphasizing the importance of monitoring instrument performance. In the 1970s, hydrophones and steel spheres were used as alternative references for calibrations. Substantial variations of system performance were observed, however, and gradually it was accepted that the use of hydrophones was inappropriate, because their performance varied more than that of the instruments being calibrated. Not until optimized reference targets were introduced in ca. 1980, was it possible to monitor the stability of acoustic-survey equipment with an acceptable degree of confidence. For the first time, the true, long-term stability of transducers, including ageing effects, could be accurately measured. This paper gives examples of calibration time-series for several Norwegian research vessels operating in various regions from Arctic to tropical waters.
A Novel Plant Leucine-Rich Repeat Receptor Kinase Regulates the Response ofMedicago truncatulaRoots to Salt Stress
Authors: de Lorenzo Laura , Merchan Francisco , Laporte Philippe , Thompson Richard , Clarke Jonathan , Sousa Carolina , Crespi Martín 
Published: February 2009

AbstractIn plants, a diverse group of cell surface receptor-like protein kinases (RLKs) plays a fundamental role in sensing external signals to regulate gene expression. Roots explore the soil environment to optimize their growth via complex signaling cascades, mainly analyzed in Arabidopsis thaliana. However, legume roots have significant physiological differences, notably their capacity to establish symbiotic interactions. These major agricultural crops are affected by environmental stresses such as salinity. Here, we report the identification of a leucine-rich repeat RLK gene, Srlk, from the legume Medicago truncatula. Srlk is rapidly induced by salt stress in roots, and RNA interference (RNAi) assays specifically targeting Srlk yielded transgenic roots whose growth was less inhibited by the presence of salt in the medium. Promoter-β-glucuronidase fusions indicate that this gene is expressed in epidermal root tissues in response to salt stress. Two Srlk-TILLING mutants also failed to limit root growth in response to salt stress and accumulated fewer sodium ions than controls. Furthermore, early salt-regulated genes are downregulated in Srlk-RNAi roots and in the TILLING mutant lines when submitted to salt stress. We propose a role for Srlk in the regulation of the adaptation of M. truncatula roots to salt stress.
A Bacterial-Type ABC Transporter Is Involved in Aluminum Tolerance in Rice
Authors: Huang Chao Feng , Yamaji Naoki , Mitani Namiki , Yano Masahiro , Nagamura Yoshiaki , Ma Jian Feng 
Published: February 2009

AbstractAluminum (Al) toxicity is a major factor limiting crop production in acidic soil, but the molecular mechanisms of Al tolerance are poorly understood. Here, we report that two genes, STAR1 (for sensitive to Al rhizotoxicity1) and STAR2, are responsible for Al tolerance in rice. STAR1 encodes a nucleotide binding domain, while STAR2 encodes a transmembrane domain, of a bacterial-type ATP binding cassette (ABC) transporter. Disruption of either gene resulted in hypersensitivity to aluminum toxicity. Both STAR1 and STAR2 are expressed mainly in the roots and are specifically induced by Al exposure. Expression in onion epidermal cells, rice protoplasts, and yeast showed that STAR1 interacts with STAR2 to form a complex that localizes to the vesicle membranes of all root cells, except for those in the epidermal layer of the mature zone. When expressed together in Xenopus laevis oocytes, STAR1/2 shows efflux transport activity specific for UDP-glucose. Furthermore, addition of exogenous UDP-glucose rescued root growth in the star1 mutant exposed to Al. These results indicate that STAR1 and STAR2 form a complex that functions as an ABC transporter, which is required for detoxification of Al in rice. The ABC transporter transports UDP-glucose, which may be used to modify the cell wall.
FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non‐Hodgkin lymphoma
Authors: Park Myoung‐Ja , Taki Tomohiko , Oda Megumi , Watanabe Tomoyuki , Yumura‐Yagi Keiko , Kobayashi Ryoji , Suzuki Nobuhiro , Hara Junichi , Horibe Keizo , Hayashi Yasuhide 
Published: February 2009

SummaryMutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T‐ALL) and 14 T cell non‐Hodgkin lymphoma (T‐NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL‐97 and NHL‐98. FBXW7 and/or NOTCH1 mutations were found in 22 (40·0%) of 55 T‐ALL and 7 (50·0%) of 14 T‐NHL patients. FBXW7 mutations were found in 8 (14·6%) of 55 T‐ALL and 3 (21·4%) of 14 T‐NHL patients, and NOTCH1 mutations in 17 (30·9%) of 55 T‐ALL and 6 (42·9%) of 14 T‐NHL patients. Three (5·4%) T‐ALL and two (1·4%) T‐NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five‐year event‐free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95·5% (95% CI, 71·9–99·4%) and 100% respectively, suggesting that T‐ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63·6%, P = 0·007 and 78·8%, P = 0·023, respectively).
Colocalization of the VEGF‐R2 and the common IL‐3/GM‐CSF receptor beta chain to lipid rafts leads to enhanced p38 activation
Authors: Saulle Ernestina , Riccioni Roberta , Coppola Simona , Parolini Isabella , Diverio Daniela , Riti Viviana , Mariani Gualtiero , Laufer Stefan , Sargiacomo Massimo , Testa Ugo 
Published: February 2009

SummaryPrevious studies suggested an important role for vascular endothelial growth factor (VEGF) and its receptors in postnatal haemopoiesis. However, it is unclear how VEGF receptor (VEGFR) signalling could interact with that issued from the activation of haematopoietic growth factor receptors. To elucidate this point we explored VEGF‐R2 and granulocyte‐macrophage colony‐stimulating factor receptor (GM‐CSFR) membrane localization and cell signalling in TF1‐KDR cells (TF1 leukaemic cells that overexpress VEGF‐R2/KDR). Activation of either GM‐CSFR or VEGF‐R2 was shown to determine the migration of both receptor elements (VEGF‐R2 and the common β‐chain of the GM‐CSFR) to lipid rafts. The study of receptor phosphorylation showed that GM‐CSF induced the phosphorylation of its own receptor and the transphosphorylation of VEGF‐R2; on the other hand, VEGF triggered the phosphorylation of its receptor and transphosphorylated the β‐chain of the GM‐CSFR. Co‐stimulation of TF1‐KDR cells with both GM‐CSF and VEGF‐A resulted in massive migration of both the common GM‐CSFR β‐chain and VEGF‐R2 to lipid rafts and sustained p38 mitogen‐activated protein kinase activation. Disruption of lipid rafts inhibited the capacity of both GM‐CSF and VEGF‐A to activate p38. Experiments with specific p38 inhibitors showed that p38 activation was required to sustain the VEGF‐ and GM‐CSF‐dependent proliferation of TF1‐KDR and the survival of primary acute myeloid leukaemia blasts.
A suppressive oligodeoxynucleotide inhibits ocular inflammation
Authors: Fujimoto C , Klinman D M , Shi G , Yin H , Vistica B P , Lovaas J D , Wawrousek E F , Igarashi T , Chan C-C , Gery I 
Published: February 2009

SummarySynthetic oligodeoxynucleotides (ODN) expressing ‘suppressive’ TTAGGG motifs down-regulate a variety of proinflammatory and T helper type 1 (Th1)-mediated pathological immune responses. The ability of the archetypal suppressive ODN A151 to inhibit ocular inflammation was examined in two murine models: experimental autoimmune uveitis, induced by immunization with a retinal antigen, interphotoreceptor retinoid-binding protein (IRBP) and adoptively transferred ocular inflammation, induced by transferring Th1 cells specific to hen egg lysozyme (HEL) into recipient mice that express HEL in their eyes. A151 treatment suppressed the inflammation in both models. In addition, A151 inhibited IRBP-specific cytokine production and lymphocyte proliferation in mice immunized with IRBP. These findings suggest that suppressive ODN affects both afferent and efferent limbs of the immunopathogenic process and may be of use in the treatment of autoimmune ocular inflammation.
Mycobacterium boviswith different genotypes and from different hosts induce dissimilar immunopathological lesions in a mouse model of tuberculosis
Authors: Aguilar León D , Zumárraga M J , Jiménez Oropeza R , Gioffré A K , Bernardelli A , Orozco Estévez H , Cataldi A A , Hernández Pando R 
Published: February 2009

SummaryWith the hypothesis that genetic variability of Mycobacterium bovis could influence virulence and immunopathology, five M. bovis strains were selected from an epidemiological study in Argentina on the basis of their prevalence in cattle and occurrence in other species. We then determined the virulence and the immunopathology evoked by these strains in a well-characterized mouse model of progressive pulmonary tuberculosis. The reference strain AN5 was used as a control. BALB/c mice infected with this M. bovis reference strain showed 50% survival after 4 months of infection, with moderate bacillary counts in the lung. Two weeks after inoculation, it induced a strong inflammatory response with numerous granulomas and progressive pneumonia. In contrast, strain 04-303, isolated from a wild boar, was the most lethal and its most striking feature was sudden pneumonia with extensive necrosis. Strain 04-302, also isolated from wild boar but with a different spoligotype, induced similar pathology but to a lesser extent. In contrast, strains 534, V2 (both from cattle) and 02-2B (from human) were less virulent, permitting higher survival after 4 months of infection and limited tissue damage. Strain AN5 and the cattle and human isolates induced rapid, high and stable expression of interferon (IFN)-γ and inducible nitric oxide synthase (iNOS). In contrast, the more virulent strains induced lower expression of IFN-γ, tumour necrosis factor-α and iNOS. Interestingly, these more virulent strains induced very low expression of murine beta defensin 4 (mBD-4); whereas, the control strain AN5 induced progressive expression of this anti-microbial peptide, peaking at day 120. The less virulent strains induced high mBD-4 expression during early infection. Thus, as reported with clinical isolates of M. tuberculosis, M. bovis also showed variable virulence. This variability can be attributed to the induction of a different pattern of immune response.
Skeletal consequences of familial hypocalciuric hypercalcaemia vs. primary hyperparathyroidism
Authors: Christensen Signe Engkjær , Nissen Peter H. , Vestergaard Peter , Heickendorff Lene , Rejnmark Lars , Brixen Kim , Mosekilde Leif 
Published: February 2009

SummaryObjectives  Bone metabolism is only superficially described in familiar hypocalciuric hypercalcaemia (FHH). We describe and compare biochemical and osteodensitometric variables in FHH and primary hyperparathyroidism (PHPT) and assess whether they can improve the diagnostic discrimination between the groups.Design  Cross‐sectional.Patients  Sixty‐six FHH patients with known calcium‐sensing receptor (CASR) gene mutations and 147 PHPT patients.Measurements  We determined calcium, creatinine, phosphate, magnesium, parathyroid hormone (PTH), 25OHD, 1,25(OH)2D and alkaline phosphatase (AP) in plasma, NTx/creatinine ratio in urine and calculated the calcium/creatinine clearance ratio (CCCR). We performed dual energy X‐ray absorptiometry at the lumbar spine, hip, forearm and whole body.Results  When compared with normal controls, the FHH patients had increased levels of PTH and AP with normal U‐NTx and regional Z‐scores. Increased phenotypic expression of CASR mutations in terms of hypercalcaemia was associated with higher lumbar spine bone mineral density, but not with bone markers. FHH were younger and leaner than the PHPT patients. They had comparable plasma Ca2+ and 25OHD, but lower levels of PTH, 1,25(OH)2D, AP and U‐NTx. They had higher Z‐scores in the hip and in the forearm. We achieved the best discrimination between groups by multiplying CCCR with AP, 1,25(OH)2D and PTH, but the difference between the area under the curves by receiver operating characteristic analysis remained insignificant.Conclusion  Familiar hypocalciuric hypercalcaemia is associated with increased PTH and AP compared to normal controls, but not with bone loss irrespective of the severity of the CASR mutations. A multiplicative model including CCCR, AP, 1,25(OH)2D and PTH insignificantly improved the power of the CCCR to differentiate between FHH and PHPT. However, we still recommend CASR gene analysis in patients with a CCCR <0·020.
Activational effects of sex hormones on cognition in men
Authors: Ulubaev A. , Lee D. M. , Purandare N. , Pendleton N. , Wu F. C. W. 
Published: February 2009

SummaryBackground  Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer’s.In normally ageing men, these age‐related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre‐ and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility.Methods  This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross‐sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined.Conclusions  Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis including receptors, enzymes and other hormones.
Lignin dynamics in two 13C‐labelled arable soils during 18 years
Authors: Hofmann A. , Heim A. , Christensen B. T. , Miltner A. , Gehre M. , Schmidt M. W. I. 
Published: February 2009

SummaryLignin has long been considered a relatively stable component of soil organic matter. However, recent studies suggest that lignin may turn over within years to decades in arable soil. Here we analysed lignin concentrations in an 18‐year field experiment under continuous silage maize, where two soils were sampled at six points in time. Our objectives were to examine the long‐term dynamics of (i) lignin derived from a previous C3‐vegetation and (ii) lignin derived from maize, as influenced by two levels of maize biomass input. Total lignin concentrations in soil were quantified by gas chromatography of lignin cupric oxide oxidation products. Compound‐specific 13C isotope analysis allowed discrimination between C3‐derived lignin and maize‐derived lignin. Degradation dynamics of C3‐derived lignin were independent of biomass input level, suggesting that priming did not affect soil lignin concentrations. After 18 years, approximately two‐thirds of the initial C3‐derived lignin remained in the soils, whereas, on average, 10% of the recent maize‐derived lignin input was retained. We suggest that lignin is effectively stabilized in these arable soils, although the mechanisms involved remain unclear.
Trends in soil organic matter contents in Dutch grasslands and maize fields on sandy soils
Authors: Hanegraaf M. C. , Hoffland E. , Kuikman P. J. , Brussaard L. 
Published: February 2009

SummaryThere is considerable concern in Europe that soil organic matter (SOM) contents are declining, which would threaten both agriculture and the environment. We performed a trend analysis of SOM contents in sandy soils, using historic data from routine agricultural soil analyses. Data were selected from grass, grass‐maize rotation and maize fields in four adjacent provinces that had been sampled four to five times during the period 1984–2004. Absolute (at least 1%) and relative changes (SOMt=20/SOMt=0) were calculated and regressed against initial SOM contents. Mean SOM content showed a north‐south gradient per cropping system. We found no single uniform trend in SOM contents for any of the three systems. Over the 20‐year period, SOM declined in c. 25% of all grasslands, amounting to 185 000 of the 635 000 hectares of land under grass and forage crops in the four provinces, and increased in a total of 267 000 hectares. Carbon accumulation in grassland sandy soils was calculated at 39 g C m−2 year−1 (top 5 cm). For the grasslands, initial SOM contents were linearly and negatively related to absolute changes in SOM; the relation with the relative change was best explained by using log‐transformed values of SOM. We conclude that in grassland soils in the Netherlands, conservation of SOM requires identification of high‐risk fields rather than high‐risk areas. For continuous maize on sandy soils, the entire area may be denoted as high‐risk, because all fields could reach the critical limit of 3.4% SOM in the near future.
40Ar/ 39Ar dating of Penninic Front tectonic displacement (W Alps) during the Lower Oligocene (31–34 Ma)
Authors: Simon‐Labric T. , Rolland Y. , Dumont T. , Heymes T. , Authemayou C. , Corsini M. , Fornari M. 
Published: February 2009

AbstractDirect absolute dating of the Penninic Frontal Thrust tectonic motion is achieved using the 40Ar/39Ar technique in the Pelvoux Crystalline Massif (Western Alps). The dated phengites were formed syn‐kinematically in shear zones. They underline the brittle‐ductile stretching lineation, pressure‐shadow fibres and slickensides consistent with underthrusting of the European continental slab below the propagating Penninic Thrust. Chlorite–phengite thermobarometry yields 10–15 km and T∼280 °C, while 40Ar/39Ar phengite ages mainly range between 34 and 30 Ma, with one younger age at 27 Ma. This Early Oligocene age range matches a major tectonic rearrangement of the Alpine chain. Preservation of prograde 40Ar/39Ar ages is ascribed to passive exhumation of the Pelvoux shear zone network, sandwiched between more external thrusts and the Penninic Front reactivated as an E‐dipping detachment fault. Partial resetting in the Low Temperature part of argon spectra below 24 Ma is ascribed to brittle deformation and alteration of phengites.