bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term Callovian–Oxfordian sea‐level changes and sedimentation in the Iberian carbonate platform (Jurassic, Spain): possible eustatic implications
Authors: Ramajo Javier , Aurell Marc 
Published: February 2008

ABSTRACTFacies analysis across the carbonate platform developed during the Callovian–Oxfordian in the northern Iberian basin (Jurassic, Northeast Spain) is used to characterize successive stages of sedimentary evolution, including palaeoenvironmental reconstructions showing the distribution of a wide spectrum of facies, from ferruginous oolitic, peloidal, spongiolithic to intraclastic. The studied successions consist of two long‐term transgressive–regressive cycles bounded by a major unconformity with a major gap, comprising at least the upper Lamberti (Callovian) and Mariae (Oxfordian) Zones. Major transgressive peaks of these two cycles occurred at the end of the Early Callovian (late Gracilis Zone) and at the end of the Middle Oxfordian. The Callovian and Oxfordian successions were further divided into three and seven higher frequency cycles, respectively. The modelling of two sections (i.e. Ricla and Tosos) located 40 km apart in the more subsident open platform areas, allows the reconstruction of two curves showing a similar evolution of long‐term sea‐level changes that are in theory eustatic, though subject to uncertainties derived form the assumptions required for their construction. The changes affecting the northern Iberian basin seem to reflect nearly homogeneous subsidence (rates around 2 cm kyr−1) combined with possible eustatic changes including an Early Callovian rise, a fall at the middle Callovian–earliest Oxfordian (i.e. the Anceps–Mariae Zones), with average long‐term rates around 2 cm kyr−1 (total fall of 40–60 m), a period of lowstand at the Early–Middle Oxfordian transition and a long‐term rise at the Middle–Late Oxfordian transition (Transversarium and Bifurcatus Zones). Facies distribution across the Iberian platform indicates a progressive Middle–Late Callovian relative sea‐level fall rather than a rapid relative sea‐level fall at the end of the Callovian. After this falling episode, the progressive onlap over the swell areas during the Early Oxfordian and at the beginning of the Middle Oxfordian indicates a period of accommodation gain, which is explained by the combined effects of continuous subsidence across the platform and reduced sedimentation rates in spite of the possible eustatic lowstand. Eustatic lowstand, combined with other factors (ocean water circulation, volcanism) could help to explain the loss of carbonate production during the latest Callovian–Early Oxfordian, previous to the widespread eustatic rise and warning recorded at the onset of the Transversarium Zone (Middle Oxfordian).
U–Pb zircon and 40Ar–39Ar K‐feldspar dating of syn‐sedimentary volcanism of the Neoproterozoic Maricá Formation: constraining the age of foreland basin inception and inversion in the Camaquã Basin of southern Brazil
Authors: Borba André W. , Mizusaki Ana Maria P. , Santos João Orestes S. , McNaughton Neal J. , Onoe Artur T. , Hartmann Léo A. 
Published: February 2008

ABSTRACTNew U–Pb zircon and 40Ar–39Ar K‐feldspar data are presented for syn‐sedimentary volcanogenic rocks from the Neoproterozoic Maricá Formation, located in the southern Brazilian shield. Seven (of nine) U–Pb sensitive high‐resolution ion microprobe analyses of zircons from pyroclastic cobbles yield an age of 630.2±3.4 Ma (2σ), interpreted as the age of syn‐sedimentary volcanism, and thus of the deposition itself. This result indicates that the Maricá Formation was deposited during the main collisional phase (640–620 Ma) of the Brasiliano II orogenic system, probably as a forebulge or back‐bulge, craton‐derived foreland succession. Thus, this unit is possibly correlative of younger portions of the Porongos, Brusque, Passo Feio, Abapã (Itaiacoca) and Lavalleja (Fuente del Puma) metamorphic complexes. Well‐defined, step‐heating 40Ar–39Ar K‐feldspar plateau ages obtained from volcanogenic beds and pyroclastic cobbles of the lower and upper successions of the Maricá Formation yielded 507.3±1.8 Ma and 506.7±1.4 Ma (2σ), respectively. These data are interpreted to reflect total isotopic resetting during deep burial and thermal effects related to magmatic events. Late Middle Cambrian cooling below ca. 200 °C, probably related to uplift, is tentatively associated with intraplate effects of the Rio Doce and/or Pampean orogenies (Brasiliano III system). In the southern Brazilian shield, these intraplate stresses are possibly related to the dominantly extensional opening of a rift or a pull‐apart basin, where sedimentary rocks of the Camaquã Group (Santa Bárbara and Guaritas Formations) accumulated.
Camellia japonica suppresses immunoglobulin E‐mediated allergic response by the inhibition of Syk kinase activation in mast cells
Authors: Lee J‐H. , Kim J‐W. , Ko N‐Y. , Mun S‐H. , Kim D‐K. , Kim J‐D. , Kim H‐S. , Lee K‐R. , Kim Y‐K. , Radinger M. , Her E. , Choi W‐S. 
Published: February 2008

SummaryBackground
Novel approaches are being explored to develop new therapies for various allergic diseases. Complementary and alternative medicines are considered to be promising avenues for the development of such new therapies.Objectives
To investigate the effect of many Korean plants on the IgE‐mediated allergic response in mast cells and in vivo, and its mechanism of action.Materials and methods
The anti‐allergic activity was tested by evaluating effects on degranulation of mast cells in culture and passive cutaneous anaphylaxis (PCA) in vivo. Its mechanism of action was investigated by immunoblotting analysis, immunoprecipitation, RT‐PCR, and other molecular biological approaches in mast cells.Results
We screened approximately 100 natural plant extracts collected in Korea for in vitro anti‐allergic activity. The leaf extract of Camellia japonica (LECJ) exhibited the most potent effect on degranulation in antigen‐stimulated rodent and human mast cells. LECJ reversibly inhibited degranulation in a dose‐dependent manner, with IC50 values of ∼50 μg/mL for the mast cells, and it also suppressed the expression and secretion of TNF‐α and IL‐4 in rat basophilic leukaemia‐2H3 mast cells. In agreement with its in vitro activity, LECJ significantly inhibited mast cell‐mediated PCA in an animal model. LECJ inhibited activating phosphorylation of tyrosine Y371 on Syk kinase, indicating that LECJ inhibits the activity of Src‐family kinases in mast cells. In the in vitro kinase assay, LECJ directly inhibited Lyn kinase, the major Src‐family kinase in the cells. It also suppressed Akt and MAP kinases, which are critical for the production of various pro‐inflammatory cytokines in mast cells. In high‐performance liquid chromatography analysis, quercetin‐3‐β‐d‐glucoside and eugenol were identified as the major active components.Conclusion
The present results strongly suggest that the anti‐allergic activity of LECJ is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Src‐family kinase in mast cells and it may be useful for the treatment of mast cell‐related immediate and delayed allergic diseases.
Post‐allergen challenge inhibition of poly(ADP‐ribose) polymerase harbors therapeutic potential for treatment of allergic airway inflammation
Authors: Naura A. S. , Hans C. P. , Zerfaoui M. , You D. , Cormier S. A. , Oumouna M. , Boulares A. H. 
Published: February 2008

SummaryBackground
Identifying therapeutic drugs that block the release or effects of T‐helper type 2 (Th2) cytokines after allergen exposure is an important goal for the treatment of allergic inflammatory diseases including asthma. We recently showed, using a murine model of allergic airway inflammation, that poly(ADP‐ribose) polymerase (PARP) plays an important role in the pathogenesis of asthma‐related lung inflammation. PARP inhibition, by single injection of a novel inhibitor, thieno[2,3‐c]isoquinolin‐5‐one (TIQ‐A), before ovalbumin (OVA) challenge, prevented airway eosinophilia in C57BL/6 mice with concomitant suppression of Th2 cytokine production and mucus secretion.Objective
To evaluate the efficacy of the drug when it is given after OVA challenge for its possible therapeutic potential.Methods
This study was conducted using a murine model of allergic airway inflammation.Results
A single injection of TIQ‐A (6 mg/kg) one or 6 h post‐allergen challenge conferred similar reduction in OVA challenge‐induced eosinophilia. More significantly, post‐allergen challenge administration of the drug exerted even better suppression on the production of IL‐4, IL‐5, IL‐13, and IgE and prevented airway hyperresponsiveness to inhaled‐methacholine. The significant decrease in IL‐13 was accompanied by a complete absence of airways mucus production indicating a potential protection against allergen‐induced airway remodelling.Conclusion
The coincidence of the inflammation trigger and the time of drug administration appear to be important for the drug's more pronounced protection. The observed time window for efficacy, 1 or 6 h after allergen challenge may be of great clinical interest. These findings may provide a novel therapeutic strategy for the treatment of allergic airway inflammation, including asthma.
The impact of fasting and treatment omission on susceptibility to hypoglycaemia in children and adolescents with GH and cortisol insufficiency
Authors: Johnstone Helen C. , McNally Richard J. Q. , Cheetham Tim D. 
Published: February 2008

SummaryObjective  Hypoglycaemia may be a frequent occurrence in young GH deficient patients and so we studied the response to fasting in children and adolescents with GH and/or cortisol deficiency.Methods  A total of 20 patients (2–18 years) fasted for 14 h (22·00–12·00 h) on two occasions as part of a randomized cross‐over study. Fourteen had pituitary hormone deficiency (PHD) including GH deficiency (GHD). Of the 14 patients, seven were ACTH sufficient (PHDC+) and seven ACTH deficient (PHDC–). Six had primary adrenal failure (PAF). Subjects administered or omitted their normal dose of evening GH and/or morning hydrocortisone. Glucose, insulin, GH, cortisol, ketones and catecholamines were measured at 04·00 h and regularly from 07·00 to 12·00 h. Insulin sensitivity was assessed by HOMA and hypoglycaemia defined as a blood glucose (BG) ≤ 3·3 mmol/l.Results  BG was related to age and body mass index on treatment but no subject became hypoglycaemic on or off therapy prior to 07·00 h. Five children (aged 3, 4, 7, 8 and 11 years) were hypoglycaemic between 07·00 and 12·00 h off treatment. There was a positive relationship between GH AUC and minimum BG in patients with PHD on treatment (r2 = 0·45, P = 0·012) with increased insulin sensitivity off treatment. Increased cortisol levels were seen in PHDC+ patients off GH (P < 0·001). A negative relationship was observed between minimum BG and adrenaline (r2 = 0·37, P = 0·01), ketone bodies (r2 = –0·20, P = 0·05) and NEFA (r2 = –0·35, P = 0·02). Noradrenaline levels were reduced in patients with PHDC–. Low BMI (on treatment) and young age (off treatment) were determinants of low BG levels in a multiple regression model.Conclusions  Unrecognized overnight hypoglycaemia in children and adolescents on pituitary hormone replacement is uncommon but BG levels quickly become abnormal when treatment and meals are omitted. The insulin antagonistic actions of GH are important in preventing hypoglycaemia. Patients with PHD have altered sympathetic nerve activity.
Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients
Authors: Garin Intza , Rica Itxaso , Estalella Itziar , Oyarzabal Mirentxu , Rodríguez‐Rigual Mercedes , Pedro Jose Ignacio San , Pérez‐Nanclares Gustavo , Fernández‐Rebollo Eduardo , Busturia Maria Angeles , Castaño Luis , De Nanclares Guiomar Pérez ,   Spanish MODY Group
Published: February 2008

SummaryObjective  The aim of this study was to characterize glucokinase (GCK) alterations in maturity‐onset diabetes of the young 2 (MODY2)‐suspected patients and to investigate their clinical characteristics in relation to the parental origin of the mutation.Patients and methods  We studied a group of 57 unrelated Spanish patients presenting with MODY2 phenotype. Patients without mutation in the coding region of the GCK gene were screened for rearrangements by Multiplex Ligation‐dependent Probe Amplification (MLPA). After classification according to the parental origin of the mutation, clinical characteristics were compared between the groups.Results  We detected a point mutation or small deletion or insertion of the GCK gene in 47 patients (82·5%); 19 mutations were novel. In addition, we found a whole‐gene deletion by MLPA. Patients carrying a GCK gene defect and those with MODY of unknown genetic origin shows similar phenotypes.Comparison of clinical parameters according to the origin of the mutation did not show any differences in the birth weight (BW) nor in age at diagnosis. Patients who inherited the mutation from the father had higher fasting glucose levels at diagnosis.Conclusion  Although the presence of haploinsufficiency of GCK is not a common cause of MODY2, gene dose analysis should be performed when no mutation is found.Strict maternal euglycaemia can contribute to intrauterine growth restriction and low BW when the foetus has inherited the GCK mutation from the mother. As foetal genotype in generally is not known, serial foetal abdominal scans may act as a surrogate for this.
Difference in development of medullary thyroid carcinoma among carriers of RET mutations in codons 790 and 791*
Authors: Frank‐Raue Karin , Machens Andreas , Scheuba Christian , Niederle Bruno , Dralle Henning , Raue Friedhelm ,   the German MEN2 Study Group
Published: February 2008

SummaryObjectives  Hereditary medullary thyroid carcinoma (MTC) is caused by germ‐line mutations in the RET proto‐oncogene. Our study addresses the difference in development of MTC between rare mutations in RET codons 790, 791 and 804.Design  We evaluated tumour stage, calcitonin levels, biochemical cure rates and associated endocrinopathies in 153 German/Austrian patients with RET 790 (n = 47), 791 (n = 56) and 804 mutations (n = 50), divided into index‐ and screening groups.Results  Age at diagnosis in index‐patients did not differ significantly among the three codon groups (medians of 57, 61 and 53 years). Tumour stage at diagnosis was significantly less advanced with codon 791 (n = 22) than 790 (n = 16) and 804 (n = 16) mutations (P = 0·001). In screening patients, age at diagnosis did not differ significantly among the three groups (medians 19, 24 and 32 years). Tumour stage at diagnosis was also significantly less advanced with codon 791 (n = 34) than 790 (n = 31) and 804 (n = 34) (P = 0·032). Preoperative basal calcitonin levels were significantly lower in codon 791 carriers compared to codon 790 carriers, and cure rates were significantly higher in both index (75%vs. 31%; P = 0·03) and screening patients (100%vs. 75%; P = 0·015). Additional endocrinopathies were observed only with codon 791 carriers (four pheochromocytomas and two hyperparathyroidism).Conclusion  There is a significant difference in MTC development with less extensive C‐cell disease, higher cure rate and more frequent additional endocrinopathies in carriers of RET codon 791 mutations compared with carriers of codons 790 and 804 mutations. This information should be considered when age of prophylactic thyroidectomy is discussed.
Host plant variation in plant‐mediated indirect effects: moth boring‐induced susceptibility of willows to a specialist leaf beetle
Authors: UTSUMI SHUNSUKE , OHGUSHI TAKAYUKI 
Published: February 2008

Abstract 1. We examined the plant‐mediated indirect effects of the stem‐boring moth Endoclita excrescens (Lepidoptera: Hepialidae) on the leaf beetle Plagiodera versicolora (Coleoptera: Chrysomelidae) in three willow species, Salix gilgiana, S. eriocarpa, and S. serissaefolia.2. When the stem‐boring moth larvae damaged stems in the previous year, willows were stimulated to produce vigorously growing lateral shoots on these stems. These new lateral shoots were significantly longer and the upper leaves had significantly higher nitrogen and water content than current‐year shoots on unbored stems, although the carbon content and leaf dry mass were not different between lateral and current‐year shoots.3. In the field, leaf beetle larvae and adults had significantly greater densities on lateral shoots of bored stems than on current‐year shoots of unbored stems. A laboratory experiment showed that female beetles had significantly greater mass and fecundity when fed on leaves of newly‐emerged lateral shoots. Thus, the stem‐boring moth had a positive effect on the temporally and spatially separated leaf beetle by increasing resource availability by inducing compensatory regrowth.4. The strength of the indirect effects on the density and performance of the leaf beetle differed among willow species, because there was interspecific variation in host quality and herbivore‐induced changes in plant traits. In particular, we suggest that the differences in magnitude of the changes among willow species in shoot length and leaf nitrogen content greatly affected the strength of the plant‐regrowth mediated indirect effect, coupled with host‐plant preference of the leaf beetle.
Co‐inheritance of a PKD1 mutation and homozygous PKD2 variant: a potential modifier in autosomal dominant polycystic kidney disease
Authors: Dedoussis G. V. Z. , Luo Y. , Starremans P. , Rossetti S. , Ramos A. J. , Cantiello H. F. , Katsareli E. , Ziroyannis P. , Lamnissou K. , Harris P. C. , Zhou J. 
Published: February 2008

ABSTRACTBackground  Autosomal dominant polycystic kidney disease (ADPKD), which is caused by mutations in polycystins 1 (PC1) and 2 (PC2), is one of the most commonly inherited renal diseases, affecting ~1 : 1000 Caucasians.Materials and methods  We screened Greek ADPKD patients with the denaturing gradient gel electrophoresis (DGGE) assay and direct sequencing.Results  We identified a patient homozygous for a nucleotide change c.1445T > G, resulting in a novel homozygous substitution of the non‐polar hydrophobic phenylalanine to the polar hydrophilic cysteine in exon 6 at codon 482 (p.F482C) of the PKD2 gene and a de‐novo PKD1 splice‐site variant IVS21–2delAG. We did not find this PKD2 variant in a screen of 280 chromosomes of healthy subjects, supporting its pathogenicity. The proband's parents did not have the PKD1 mutation. Real‐time PCR of the PKD2 transcript from a skin biopsy revealed 20‐fold higher expression in the patient than in a healthy subject and was higher in the patient's peripheral blood mononuclear cells (PBMCs) than in those of her heterozygote daughter and a healthy subject. The greater gene expression was also supported by Western blotting. Inner medullar collecting duct (IMCD) cells transfected with the mutant PKD2 mouse gene presented a perinuclear and diffuse cytoplasmic localization compared with the wild type ER localization. Patch‐clamping of PBMCs from the p.F482C homozygous and heterozygous subjects revealed lower polycystin‐2 channel function than in controls.Conclusions  We report for the first time a patient with ADPKD who is heterozygous for a de novo PKD1 variant and homozygous for a novel PKD2 mutation.
Elevation of matrix metalloproteinases and interleukin‐6 in the culprit coronary artery of myocardial infarction
Authors: Suzuki H. , Kusuyama T. , Sato R. , Yokota Y. , Tsunoda F. , Sato T. , Shoji M. , Iso Y. , Koba S. , Katagiri T. 
Published: February 2008

ABSTRACTBackground  Interleukin‐6 (IL‐6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI.Materials and methods  One hundred and twenty‐two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age‐matched patients.Results  The serum levels of IL‐6 (P < 0·05), tumour necrosis factor‐α (P < 0·005), MMP‐1 (P < 0·001), MMP‐13 (P < 0·001), soluble intercellular adhesion molecule‐1 (P < 0·005), and soluble vascular cellular adhesion molecule‐1 (P < 0·05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL‐6 (P < 0·001), MMP‐1 (P < 0·001), and MMP‐13 (P < 0·05) compared to the peripheral blood of AMI. Serum IL‐6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6–12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12–24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin‐1β and MMP‐2.Conclusions  The levels of MMP‐1, MMP‐13 and IL‐6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI.
Validation study of nasal nitric oxide measurements using a hand‐held electrochemical analyser
Authors: Maniscalco M. , Laurentiis G. de , Weitzberg E. , Lundberg J. O. , Sofia M. 
Published: February 2008

ABSTRACTBackground  Exhaled nitric oxide (NO) measurement is a simple and non‐invasive method for monitoring airway inflammation. Similarly, nasal NO has been proposed as a surrogate marker in inflammatory diseases of the upper airways, e.g. allergic rhinitis. A new portable analyser using an electrochemical sensor has been developed for measurements of exhaled NO, and its reproducibility and comparison with other analysers has been tested recently in healthy subjects and in patients with lower airways disease. The application of this hand‐held analyser in nasal NO analysis was tested and compared to the gold standard represented by a chemiluminescence analyser.Materials and methods  Thirty subjects including 15 patients with allergic rhinitis (AR) and 15 healthy subjects (HS) were studied. The intraindividual variability, calculated as the difference in nasal NO levels between two measurements from a single nasally exhaled breath manoeuvre, and the comparison between the electrochemical analyser (NIOX MINO, Aerocrine) and a chemiluminescence analyser (NOA, Sievers) were performed.Results  In AR patients mean nasal NO was 59·0 ± 16·3 p.p.b. with the MINO and 58·3 ± 15·6 p.p.b. with the NOA. In HS nasal NO was 49·1 ± 10·8 p.p.b. with the MINO and 49·8 ± 8·2 p.p.b. with the NOA. The Bland‐Altman analysis showed bias values of 0·005 ± 3·6 with the 95% limits of agreement from –6·97 to 6·98 p.p.b.Conclusion  Measurements of nasal NO levels with a hand‐held electrochemical analyser are reproducible and the results are comparable to a stationary chemiluminescence analyser.