bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dual Role for Interferon‐γ in the Pathogenesis of Sjögren's Syndrome‐Like Autoimmune Exocrinopathy in the Nonobese Diabetic Mouse
Authors: Cha S. , Brayer J. , Gao J. , Brown V. , Killedar S. , Yasunari U. , Peck A. B. 
Published: December 2004

AbstractSjögren's syndrome‐like autoimmune exocrinopathy (AEC) in the nonobese diabetic (NOD) mouse progresses from a preimmune phase to an immune phase, resulting in dry mouth and/or dry eyes. In the present study, the impact of the prototypical T‐helper type 1 cytokine, interferon‐gamma (IFN‐γ), on the onset of AEC was investigated using both the IFN‐γ and the IFN‐γ receptor gene knockout mice, NOD.IFN‐γ–/– and NOD.IFN‐γR–/–, respectively. Neither the NOD.IFN‐γ–/– nor the NOD.IFN‐γR–/– mice exhibited increased acinar cell apoptosis and abnormal salivary protein expression, typically observed in parental NOD mice prior to disease. Without these preimmune phase abnormalities, NOD.IFN‐γ–/– and NOD.IFN‐γR–/– mice showed no subsequent autoimmune responses against the salivary glands at 20 weeks. Interestingly, real‐time polymerase chain reaction and electrophoretic gel mobility shift assays suggested that IFN‐γ and STAT1, as well as the transcriptional activity of STAT1 in NOD glands, were increased at birth. Unlike the neonatal submandibular glands of NOD or NOD‐scid mice that show abnormal glandular morphogenesis at birth, the submandibular glands of the newly constructed congenic strain, NOD‐scid.IFN‐γ–/–, were found to be normal. Taken together, IFN‐γ appears to play a critical role not only during the later immune phase of AEC, but also the early preimmune phase, independent of effector functions of immune cells. How exactly IFN‐γ functions during this period remains speculative.
Serum Concentration of the Growth Medium Markedly Affects Monocyte‐Derived Dendritic Cells' Phenotype, Cytokine Production Profile and Capacities to Stimulate in MLR
Authors: Jakobsen M. A. , Møller B. K. , Lillevang S. T. 
Published: December 2004

AbstractWe have investigated how the maturation of monocyte‐derived dendritic cells (Mo‐DC) is affected by the serum concentration of the culture medium. Day 6 DC cultured in 1% human serum were a heterogeneous population of CD1a– and CD1a+ DC that were separated by flow sorting. In contrast, Mo‐DC generated in 10% human serum formed a homogenous population of CD1a– cells. Other phenotypically immature characteristics also varied, and three subsets were still distinguishable upon maturation in LPS. Furthermore, CD1a– DC and CD1a+ DC from 1% culture conditions were excellent stimulators in MLR, while DC cultured in 10% serum were poor stimulators. Similarly, different cytokine profiles of the three subsets were identified. DC cultured in 1% serum had low expression of interleukin‐12 (IL‐12) p40 and IL‐10 mRNA at day 6. Upon maturation, expression of IL‐12 p40 mRNA was upregulated in CD1a+ DC, whereas the level remained relatively low in CD1a– DC. In contrast, DC cultured in 10% had high levels of IL‐10 mRNA at day 6 that was downregulated upon maturation. We conclude that the differentiation of monocytes into DC is significantly influenced by the serum concentration of the growth medium with effects on phenotype, cytokine profile and stimulatory activity.
Molecular phylogenetic evidence for an extracellular Cu Zn superoxide dismutase gene in insects
Authors: Parker J. D. , Parker K. M. , Keller L. 
Published: December 2004

AbstractRepresentatives of three ancient gene families of the antioxidant enzyme superoxide dismutase (SOD) can be found in most metazoans. In mammals andCaenorhabditis elegans, there is at least one gene each of the cytoplasmic, mitochondrial and extracellular lineages of SOD genes. The cytoplasmic SOD was one of the first enzymes to be implicated in ageing due to its protection against damaging oxygen free radicals. In contrast to other metazoans, insects were thought to lack a gene for the extracellular SOD. We have cloned and sequenced an SOD mRNA in the antLasius nigerthat appears to belong to this extracellular family. Subsequent searches and analyses of SOD gene sequences in insect databases revealed that insects do indeed express all three SOD genes including the extracellular form. We conclude that insects as well as other metazoans appear to have the full repertoire of the three families of SOD.
Quantitative trait loci affecting dengue midgut infection barriers in an advanced intercross line of Aedes aegypti
Authors: Gomez‐Machorro C. , Bennett K. E. , Del Lourdes Munoz M. , Black W. C. 
Published: December 2004

AbstractQuantitative trait loci (QTL) affecting the ability of the Aedes aegypti midgut to become infected with Dengue 2 virus (DEN2) were mapped in the F5 generation of an advanced intercross line (AIL). A strain of Ae. aegypti previously selected for DEN2 susceptibility was crossed to a new strain selected for refractoriness to midgut infection. In P1 and F1 parents and 147 F5 offspring, genotypes at forty‐four cDNA loci were analysed. A new sex linked QTL and a second QTL on chromosome II with genotypes subject to balancing selection were detected that condition midgut susceptibility. Alleles at these QTL contributed additively in determining susceptibility and accounted for ∼24% of the phenotypic variance. Markers associated with a midgut escape barrier were inconsistently supported.
Discrete‐element modelling of extensional fault‐propagation folding above rigid basement fault blocks
Authors: Finch Emma , Hardy Stuart , Gawthorpe Rob 
Published: December 2004

AbstractWe employed a discrete‐element technique to investigate the effects of cover strength and fault dip on the style of fault‐propagation folding above a blind normal fault. Deformation in the cover is initially characterised by an upward‐widening monocline that is often replaced, with continued slip on the basement fault, by a single, through‐going fault. Localisation on a single fault produces hangingwall synclines and footwall anticlines as a result of breaching of the earlier monocline and which do not represent ‘drag’ against the fault. As basement fault dip decreases the width of the monocline at the surface increases. Experiments varying the strength of the overburden material illustrate the control that cover strength has on both fault propagation and folding in the cover. Reduction of the strength of the cover results in: (1) the width of the monocline above the fault tip increasing, and (2) more marked footwall thinning and hangingwall thickening of beds. In contrast, an increase in cover strength results in a narrower monocline and rapid propagation of the basement fault into the cover. In multi‐layer (variable strength) experiments simultaneous faulting of competent layers and flow of weaker layers produces complex structural relationships. Faults in the cover die out up and down section and do not link to the basement fault at depth. Similarly, complex macroscopically ductile characteristics such as footwall thinning and hangingwall thickening can be juxtaposed against simple brittle fault cut‐offs. These relationships must be borne in mind when interpreting the field and seismic expression of such structures. We discuss the modelling results in terms of their implications for structural interpretation and the surficial expression of fault‐related folding in extensional settings.
Time lag of syntectonic sedimentation across an alluvial basin: theory and example from the Ebro Basin, Spain
Authors: Jones Merren A. , Heller Paul L. , Roca Eduard , Garcés Miguel , Cabrera Lluís 
Published: December 2004

AbstractWe propose and test a conceptual framework for evaluating the relative timing of different types of sedimentary indicators of tectonism in alluvial foreland basin settings. We take the first occurrence of a detrital grain from a newly exposed source‐area lithology to provide the best indicator of the onset of tectonic uplift in the source area. Source‐area unroofing may lag behind initial uplift because of the type, thickness and structure of rocks in the uplifted mountain block, drainage patterns and climate. However, once exposed, advective transport disperses grains quickly throughout fluvial systems. Because of increased subsidence rate from thrust belt loading, an increase in sedimentation rate begins coincident with tectonic load emplacement within the flexural half‐width of the basin. However, farther out into the basin increased sedimentation rates lag behind the composition signal because of time lags associated with propagation of the thrust load and attendant sediment loads into the basin. The progradation of syntectonic gravel lags behind all of these signals as a direct function of the relative proportion of gravel fraction within transported sediment and rates and geometry of subsidence, which selectively traps the coarsest grain‐size fractions in the most proximal parts of the basin.We demonstrate this signal attenuation in the syntectonic Horta–Gandesa alluvial system (late Eocene–Oligocene), exposed along the southeast margin of the Ebro Basin, Spain. The results demonstrate that: (1) the time spans between the compositional signal and the progradation of the gravel front can be geologically significant, on the order of more than a million years within as little as 20 km of the thrust front; and (2) time lags between the signals increase with distance away from the deformation front. No lag time was observed between the first appearance of a new clast composition and the arrival of gravel front when the thrust front was within a few tens of metres from the depositional site. In contrast, the time lag was 0.5–1 Myr when the thrust front was about 5–6 km away and it increased to >1 Myr when the deformation front was about 8 km away. At the most extreme position, when the thrust front was 15–20 km away, the gravel front never reached the study area.
Early Tertiary evolution of the North Alpine Foreland Basin of the Swiss Alps and adjoining areas
Authors: Kempf Oliver , Adrian Pfiffner O. 
Published: December 2004

AbstractWe present a new palaeogeographic reconstruction of the Helvetic zone based on the palinspastic restoration of 18 recently published and new retrodeformed structural cross‐sections through the Swiss Alps, Haute Savoie (France) and Vorarlberg (Austria). The reconstruction resulted in two palaeogeographic maps, one of the pre‐Mesozoic basement, the other for the sedimentary cover of the Helvetic shelf including the Nummulitic deposits of the Palaeocene–Eocene, which mark the onset of the North Alpine Foreland Basin of the Alps.Based on the palaeogeographic maps and a precise dating of the Nummulitic deposits, we established maps of the facies distribution including the estimated positions of the ancient coastlines and their evolution through time. The North Alpine Foreland Basin started as a narrow flysch basin in Palaeocene–Eocene times. Emplacement of the Penninic nappes led to the formation of a mélange on the active margin of this basin. This early foreland basin and its active margin migrated to the NW in Early Eocene times at a rate of about 10 mm yr−1. The maps also reveal a general progressive north‐ and westward propagation of the Eocene coastline between 50–34 Ma and during the Oligocene until approximately 32 Ma. Coastline propagation reveals strongly varying rates both spatially and temporally, and is ca. 1–2 mm yr−1 between 50 and 37 Ma and approximately 20 mm yr−1 between 37 and 32 Ma. Evolution and orientation of the Tertiary coastlines infers that the early development of the North Alpine Foreland Basin was mainly controlled initially by eustatic sea‐level fluctuations superimposed on flexural subsidence. After 37 Ma, we suggest a tectonically controlled coastline evolution in response to the collision of the European and Adriatic margins.
Progestogens of varying androgenicity and cardiovascular risk factors in postmenopausal women receiving oestrogen replacement therapy
Authors: Kwok See , Selby Peter L. , McElduff Patrick , Laing Ian , Mackness Bharti , Mackness Michael I. , Prais Hilary , Morgan Janet , Yates Allen P. , Durrington Paul N. , Sci F. Med 
Published: December 2004

Summaryobjective  Medroxyprogesterone (MP) was used as the progestogen in randomized clinical trials of postmenopausal hormone replacement on cardiovascular risk. To attempt to understand the lack of benefit in these trials, we have examined the effects of MP and two other progestogens, the less androgenic desogestrel (DG) and the more androgenic norethisterone (NE), on cardiovascular risk factors against a background of oestrogen therapy.design and measurements  Thirty‐four women were treated with conjugated equine oestrogens (CEE) 0·625 mg daily alone for 12 weeks, followed in random order by each of the three progestogens (DG 75 µg, MP 10 mg and NE 1 mg daily) given sequentially for three 12‐week cycles while maintaining the same CEE treatment. We measured serum lipoproteins, paraoxonase activity, C‐reactive protein (CRP), fibrinogen, fasting glucose and insulin levels at baseline, at the end of the oestrogen‐only phase and at the end of each of the combined oestrogen and progestogen phases.results  The addition of progestogens to CEE maintained the oestrogen‐induced reduction in apolipoprotein B (apo B) and lipoprotein (a) [Lp(a)], and further lowered total cholesterol (P < 0·01) and fibrinogen (P < 0·001). CEE raised serum triglyceride (P < 0·001) and CRP (P < 0·01) concentrations, which reverted towards pre‐oestrogen levels with progestogens. Progestogens significantly reduced high density lipoprotein (HDL) cholesterol (P < 0·05). NE was associated with the greatest reduction in HDL cholesterol and apo A1, but was most effective in preserving paraoxonase activity and reducing the potentially unfavourable oestrogen‐induced increases in triglycerides and CRP.conclusion  Preconceptions that more androgenic progestogens necessarily have more unfavourable effects on cardiovascular risk factors may require revision.
Specialized rules of gene transcription in male germ cells: the CREM paradigm*
Authors: Monaco Lucia , Kotaja Noora , Fienga Giulia , Hogeveen Kevin , Kolthur Ullas S. , Kimmins Sarah , Brancorsini Stefano , Macho Betina , Sassone‐Corsi Paolo 
Published: December 2004

SummarySpecialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA‐binding protein family and its associated cofactors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator cAMP response element modulator (CREM) represents an established paradigm. Somatic cell activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CREB‐binding protein. In testis, CREM transcriptional activity is controlled through interaction with a tissue‐specific partner, activator of CREM in the testis (ACT), which confers a powerful, phosphorylation‐independent activation capacity. The function of ACT was found to be regulated by the testis‐specific kinesin KIF17b. Here we discuss some aspects of the testis‐specific transcription machinery, whose function is essential for the process of spermatogenesis.
DAZL polymorphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences
Authors: Becherini L. , Guarducci E. , Degl'Innocenti S. , Rotondi M. , Forti G. , Krausz C. 
Published: December 2004

SummaryPolymorphisms in genes involved in spermatogenesis are considered potential risk factors for male infertility. Recently a polymorphism in the deleted in azoospermia‐like (DAZL) gene (T54A) was reported as susceptibility factor to oligo/azoospermia in the Chinese population. DAZL is an autosomal homologue of the Y chromosomal DAZ (deleted in azoospermia) gene cluster and both are considered master regulators of spermatogenesis. The aim of the present study was to screen (i) for mutations of the entire coding sequence of the DAZL gene in patients lacking of the DAZ gene cluster, in order to evaluate if DAZL polymorphisms may influence the AZFc deletion phenotype; (ii) for the two previously described (and eventually newly identified) single nucleotide polymorphisms (SNPs) in a large group of infertile and normospermic men of Italian origin. We failed to detect new mutations. We confirmed previous results showing no evidence for a functional role of the T12A mutation. Surprisingly, the T54A polymorphism, which was present in 7.4% of the Chinese patients was absent in our Caucasian population. This remarkable difference represent an example of how ethnic background is important also for polymorphisms involved in spermatogenesis and contributes to better select clinically relevant tests, specifically based on the ethnic origin of the infertile patients.
The pasting behaviour and freeze–thaw stability of native starch and native starch–xanthan gum pastes
Authors: Brennan Charles S. , Tan Chew K. , Kuri Victor , Tudorica Carmen M. 
Published: December 2004

SummaryThe pasting properties, gelatinization profiles and freeze–thaw stability of natural waxy maize starches, pasted in the presence of xanthan gum (XG) and resistant starch, were evaluated using a Rapid Visco Analyser, together with turbidimetric analysis. Freeze–thaw stability was determined for four cycles over a 4 weeks period. The final viscosity of the pastes was unaffected by the addition of resistant starch (RS) whereas XG additions increased final viscosity. Addition of mixtures of combinations of XG and RS increased the peak viscosity of the starch pastes. Freeze–thaw stability (as estimated by the final viscosity of the pastes during a series of four freeze–thaw cycles) was improved with the addition of XG.
Mast cells and vasculature in atopic dermatitis – potential stimulus of neoangiogenesis
Authors: Groneberg D. A. , Bester C. , Grützkau A. , Serowka F. , Fischer A. , Henz B. M. , Welker P. 
Published: December 2004

Background:  Atopic dermatitis skin lesions are characterized by inflammatory changes and epithelial hyperplasia requiring angiogenesis. As mast cells may participate in this process via bidirectional secretion of tissue‐damaging enzymes and pro‐angiogenic factors, the present study aimed to assess the occurrence and possible function of mast cells in the papillary dermis and in epidermal layers of atopic dermatitis lesions.Methods:  Semi‐thin and serial sections in combination with immunohistochemistry, histochemistry and proliferating cell nuclear antigen (PCNA)‐activity assays were used and related to epidermal thickness and targeted gene expression studies.Results:  Mast cells were located in the papillary dermis and migrated through the basal lamina into the epidermis of atopic dermatitis lesions. An increased PCNA‐activity in cells of superficial epidermal layers indicated an activation of keratinocytes and stimulation of endothelial growth. Only ∼30% of the papillary mast cells stained with the tryptase were toluidin‐blue‐positive, and ∼80% were chymase positive. A high number of mast cells expressed c‐kit. Most papillary and epidermal mast cells were localized close to endothelial cells. Vascular expression of endoglin (CD105) demonstrated neoangiogenic processes. Mast cells stimulation led to the expression of proangiogenic factors. Also, gene expression of tissue‐damaging factors such as matrix metalloproteinases was increased.Conclusions:  These data suggest that in atopic dermatitis, mast cells are abundantly localized close to and within the epidermis where they may stimulate neoangiogenesis. Via the new vessels, inflammatory cells, together with complement components and antibodies, can be transported to the epidermis to aid in the defense against environmental antigens and to maintain chronic inflammation.
Desloratadine prevents compound 48/80‐induced mast cell degranulation: visualization using a vital fluorescent dye technique
Authors: Wang Y. H. , Taché Y. , Harris A. G. , Kreutner W. , Daly A. F. , Wei J. Y. 
Published: December 2004

Background:  Desloratadine is a selective H1‐antihistamine used in the treatment of allergic rhinitis and chronic idiopathic urticaria. Desloratadine inhibits the release of allergic inflammatory mediators in vitro. We studied the impact of desloratadine on mast cell degranulation due to activation and re‐activation by the secretagogue, compound 48/80.Methods:  Rat peritoneal eluate containing 5–6% mast cells were activated by a low concentration of compound 48/80 in a medium containing the vital fluorescent dye, Sulforhodamine‐B (SFRM‐B, 200 μg/ml), which is engulfed by activated mast cells. The fluorescent image of activated mast cells was captured digitally and the total fluorescent area was analyzed when desloratadine was applied before or after compound 48/80.Results:  Mast cells were not activated by desloratadine (10−4 M), SFRM‐B (200 μg/ml), or diluent alone. A low concentration of compound 48/80 (0.125 μg/ml) induced fluorescence, while mast cells lost fluorescent images due to further degranulation on re‐exposure to compound 48/80. Desloratadine (10−8–10−4 M), inhibited compound 48/80‐induced mast cell degranulation in a concentration‐dependent manner. Desloratadine also reduced the loss of fluorescent images due to re‐exposure to compound 48/80.Conclusions:  Desloratadine may have a mast cell stabilizing effect at low concentrations in response to repeated mast cell activation in vitro.
Increased levels of urinary leukotriene E4 in children with severe atopic eczema/dermatitis syndrome
Authors: Øymar K. , Aksnes L. 
Published: December 2004

Background:  Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary leukotriene E4 (U‐LTE4) is a marker of whole‐body cysteinyl‐leukotriene production.Aims of the study:  To evaluate the role of leukotrienes in children with AEDS by measuring levels of U‐LTE4, and to evaluate whether levels of U‐LTE4 may reflect disease activity and allergic sensitization in AEDS.Methods:  U‐LTE4 was measured by enzyme‐linked immunosorbent assay in 87 children with mild (n = 32), moderate (n = 34) and severe (n = 21) AEDS, as well as in 72 nonatopic healthy controls. Fifty‐eight of the children with AEDS were sentitized to common allergens, and 29 were not.Results:  Levels of U‐LTE4 were higher in children with severe AEDS (140; 66–166 μg/mmol creatinine, median; quartiles) than in controls (52; 30–90, P < 0.05), whereas levels of U‐LTE4 in moderate and mild disease were similar to controls. U‐LTE4 levels were similar in children with or without sensitization to common allergens, but severe AEDS children with sensitization had higher levels of U‐LTE4 than those without sensitization.Conclusion:  The results suggest a role for leukotrienes in the pathogenesis of severe AEDS, and may support a role for leukotriene‐antagonists in the treatment of this disorder. Levels of U‐LTE4 may reflect the disease severity and sensitization to allergens in AEDS.