bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergic rhinitis and asthma comorbidity: ARIA classification of rhinitis does not correlate with the prevalence of asthma
Authors: Antonicelli L. , Micucci C. , Voltolini S. , Feliziani V. , Senna G. E. , Di Blasi P. , Visonà G. , De Marco R. , Bonifazi F.
Published: May 2007

Background
Allergic rhinitis and asthma comorbidity is supported by both the similar underlying pathogenesis and immunologic mechanisms. The aim of this study was to verify whether the characteristics of rhinitis classified according to the new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with the prevalence of asthma.

Methods
From 1 March to 30 June 2002, a multi‐centre cross‐sectional study was conducted by 154 allergists chosen from throughout Italy. Duration, severity of rhinitis (according to the ARIA classification) and the type of allergic sensitizations were compared with the prevalence of asthma.

Results
One thousand three hundred and twenty‐one consecutive rhinitis‐allergic patients aged 18 years or older were enrolled for the study. The majority of patients, 1060 (80.24%), were on medication at the time of their specialist visit. Mild intermittent rhinitis was diagnosed in 7.7% of patients, moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent in 63.6%. The prevalence of asthma was 48% in patients with mild intermittent rhinitis, 49.6% in moderate–severe intermittent rhinitis, 36.6% in mild persistent rhinitis and 47.5% in moderate severe persistent patients. No correlation between the ARIA categories of rhinitis and the prevalence of asthma was found.

A multivariate analysis, after adjustment for age, sex, type of sensitization, level of severity and duration of rhinitis classified according to the ARIA guidelines, demonstrated that age, over 41 years [risk ratio (RR) 1.260, 95% confidence interval (CI) 1.072–1.482] and especially over 51 years (RR 1.460, 95% CI 1.237–1.723), sensitization to indoor allergens (mite and cat), (RR 1.203, 95% CI 1.060–1.366), and polysensitization (RR 1.178, 95% CI 1.004–1.383) are significant risk factors for asthma.

Conclusion
In allergic rhinitis (AR) patients referred to a specialist, the features of AR as defined by the ARIA classification are not able to predict the presence of asthma, therefore all such patients should be assessed for asthma.
Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses
Authors: Lever R. , Hefni A. , Moffatt J. D. , Paul W. , Page C. P.
Published: May 2007

Background
Tecastemizole, a major metabolite of astemizole, is a potent and selective H1 receptor antagonist. Evidence suggests that this and certain other H1 receptor antagonists may possess anti‐inflammatory effects that are, in some cases, independent of H1 receptor antagonism.

Objective
The aim of this study was to investigate the anti‐inflammatory effects of tectastemizole in models of allergic inflammation.

Methods
Effects of tecastemizole were assessed in a murine model of allergic lung inflammation, in passive cutaneous anaphylaxis (PCA) responses in guinea‐pig skin and in in vitro assays measuring endothelial adhesion molecule expression and leucocyte–endothelial adhesion.

Results
Tecastemizole inhibited antigen‐induced eosinophil recruitment to the lungs of allergic mice in a dose‐dependent manner. Furthermore, combination of a sub‐effective dose of tecastemizole, combined with a sub‐effective dose of dexamethasone inhibited eosinophil accumulation in this model. Plasma extravasation in PCA reactions was inhibited by tecastemizole, although by a mechanism that would appear to be H1 receptor‐dependent. Cytokine‐induced endothelial intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 expression, as well as mononuclear cell adhesion to human umbilical vein endothelial cells was inhibited by tecastemazole in a manner independent of H1 receptor antagonism.

Conclusion
These data suggest that tecastemizole may have H1 receptor‐independent effects in inhibiting late‐phase inflammatory responses, while acute responses appear to be inhibited in a H1 receptor‐dependent manner. Furthermore, our data suggest an important potential steroid‐sparing role for such drugs in the treatment of allergic inflammatory conditions.
A prospective study of allergy development in 158 children and 128 adults with new extensive exposure to furred animals
Authors: Millqvist E. , Johansson Å. , Månsson T. , Bende M.
Published: May 2007

Background
There is still controversy over whether exposure to furred animals increases or decreases the risk of developing sensitization and allergic symptoms to such animals, and there is a need for further knowledge on this subject.

Objective
The aim of this study was to follow allergy development in relation to new extensive exposure to furred animals in adults and children.

Methods
A total of 286 individuals, 128 parents and 158 children, were recruited from 68 families who intended to buy a dog or a cat, or where one child of the family intended to start riding a horse. Subjects were examined before the new allergen exposure and once a year thereafter for 5 years, in all at six occasions, and they also completed questionnaires covering allergy symptoms. Serum IgE antibodies to cat, dog and horse were determined each year, and fur allergens from beds and living rooms were analysed.

Results
Two‐hundred and fifty‐six study subjects remained for evaluation, 37 of whom showed signs of allergic sensitization at the start of the study. Four children (11%) in this pre‐sensitized group developed IgE antibodies to their new animal and six (16%) to another animal. Among the 219 participants who were not sensitized when entering the study, one male adult (0.4%) developed a sensitization to his new animal, and nobody developed sensitization to other animals. Pre‐sensitized individuals had significantly more allergic symptoms at the study start, but the symptom scores did not change over time.

Conclusions
When the first year of a human's life has passed, we have no strong evidence to recommend avoidance of a domestic animal in order to prevent new allergy development, even if there are known allergies in the family or if the individual is sensitized and has allergic symptoms to another allergen. Five years exposure to new fur allergens does not seem to influence sensitization to these animals in either sensitized or non‐sensitized children and adults.
Assembly rules of ground‐foraging ant assemblages are contingent on disturbance, habitat and spatial scale
Authors: Sanders Nathan J. , Gotelli Nicholas J. , Wittman Sarah E. , Ratchford Jaime S. , Ellison Aaron M. , Jules Erik S.
Published: May 2007

Aim  A major endeavour of community ecology is documenting non‐random patterns in the composition and body size of coexisting species, and inferring the processes, or assembly rules, that may have given rise to the observed patterns. Such assembly rules include species sorting resulting from interspecific competition, aggregation at patchily distributed resources, and co‐evolutionary dynamics. However, for any given taxon, relatively little is known about how these patterns and processes change through time and vary with habitat type, disturbance history, and spatial scale. Here, we tested for non‐random patterns of species co‐occurrence and body size in assemblages of ground‐foraging ants and asked whether those patterns varied with habitat type, disturbance history, and spatial scale.

Location  Burned and unburned forests and fens in the Siskiyou Mountains of southern Oregon and northern California, USA.

Methods  We describe ground‐foraging ant assemblages sampled over two years in two discrete habitat types, namely Darlingtonia fens and upland forests. Half of these sites had been subject to a large‐scale, discrete disturbance – a major fire – in the year prior to our first sample. We used null model analyses to compare observed species co‐occurrence patterns and body‐size distributions in these assemblages with randomly generated assemblages unstructured by competition both within (i.e. at a local spatial scale) and among (i.e. at a regional scale) sites.

Results  At local spatial scales, species co‐occurrence patterns and body‐size ratios did not differ from randomness. At regional scales, co‐occurrence patterns were random or aggregated, and there was evidence for constant body‐size ratios of forest ants. Although these patterns varied between habitats and years, they did not differ between burned and unburned sites.

Main conclusions  Our results suggest that the operation of assembly rules depends on spatial scale and habitat type, but that it was not affected by disturbance history from fire.
Molecular and palaeoecological evidence for multiple glacial refugia for evergreen oaks on the Iberian Peninsula
Authors: López de Heredia U. , Carrión J. S. , Jiménez P. , Collada C. , Gil L.
Published: May 2007

Aim  A multiple glacial refugia hypothesis for Mediterranean plant species was tested with the evergreen Quercus complex (Quercus suber L., Quercus ilex L. and Quercus coccifera L.) from the Iberian Peninsula, using molecular and palaeobotanical data.

Location  The Iberian Peninsula, which is an ecologically and physiographically complex area located on the western edge of the Mediterranean Basin.

Methods  We sampled 1522 individuals from 164 populations of Q. suber, Q. ilex and Q. coccifera. A review of the recent literature on fossil pollen and charcoal records and a nested clade analysis on chloroplast DNA polymerase chain reaction‐restriction fragment length polymorphism was carried out to infer demographic and historical processes.

Results  The analysis indicates at least one glacial refugium for Q. suber in south‐western Iberia. Extensive introgression of Q. suber with Q. ilex indicates several potential refugia in eastern Iberia. Past fragmentation was followed by a restricted range flow/range expansion, suggesting multiple refugia for Q. ilex–Q. coccifera elsewhere in central and northern Iberia and multiple areas of secondary contact. This finding is consistent with fossil records.

Main conclusions  The predicted multiple refugia during glacial periods indicates the existence of secondary post‐glaciation contact areas. These areas contained complex diversity patterns resulting mainly from range expansions followed by isolation by distance. To a lesser degree, traces of restricted and long‐distance dispersal were also found.
Safety, tolerability and efficacy of peginterferon alpha‐2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial
Authors: Witthöft Th. , Möller B. , Wiedmann K. H. , Mauss St. , Link R. , Lohmeyer J. , Lafrenz M. , Gelbmann C. M. , Hüppe D. , Niederau C. , Alshuth U.
Published: May 2007

Summary. The combination treatment of peginterferon alpha‐2a (PEG‐IFN alpha‐2a; Pegasys®) plus ribavirin (RBV) is recommended as a standard care for HCV infections. Side effects and aspects of efficacy and safety have to be balanced. This study evaluates clinical practice data on safety and efficacy of HCV treatment with PEG‐IFN in combination with RBV over 24 and 48 weeks. This study was a phase III, multi‐centre, open‐label study with two treatment groups: PEG‐IFN in combination with RBV for 24 or 48 weeks. The allocation to the treatment groups was at the discretion of the investigator; 309 patients entered active treatment: 90 patients received PEG‐IFN plus RBV for 24 weeks and 219 patients PEG‐IFN plus RBV for 48 weeks. A sustained virological response (SVR) was achieved in 48.9% of all patients. Genotype 1 patients with a 48‐week combination treatment achieved an SVR of 39.9%. In the 48‐week group a low baseline viral load was associated with a higher SVR rate (47.0% vs. 32.4%). For genotype 2 or 3 patients, the SVR was 67.9%. For these patients there was no relevant difference between patients with low and high viral loads; 97.7% of the patients experienced at least one adverse event. The incidence of serious adverse events was distinctly lower in the 24‐week group (4.4% vs. 10.5%). This investigation confirms the well‐known risk–benefit ratio found in controlled studies in a clinical practice setting. The safety profile is similar and shows the highest incidence of adverse events in the first 12 weeks of treatment.
Life on the rocks
Authors: Gorbushina Anna A.
Published: May 2007

Biofilms are interface micro‐habitats formed by microbes that differ markedly from those of the ambient environment. The term ‘subaerial biofilm’ (SAB) was coined for microbial communities that develop on solid mineral surfaces exposed to the atmosphere. Subaerial biofilms are ubiquitous, self‐sufficient, miniature microbial ecosystems that are found on buildings, bare rocks in deserts, mountains, and at all latitudes where direct contact with the atmosphere and solar radiation occurs. Subaerial biofilms on exposed terrestrial surfaces are characterized by patchy growth that is dominated by associations of fungi, algae, cyanobacteria and heterotrophic bacteria. Inherent subaerial settlers include specialized actinobacteria (e.g. Geodermatophilus), cyanobacteria and microcolonial fungi. Individuals within SAB communities avoid sexual reproduction, but cooperate extensively with one another especially to avoid loss of energy and nutrients. Subaerial biofilm metabolic activity centres on retention of water, protecting the cells from fluctuating environmental conditions and solar radiation as well as prolonging their vegetative life. Atmospheric aerosols, gases and propagatory particles serve as sources of nutrients and inoculum for these open communities. Subaerial biofilms induce chemical and physical changes to rock materials, and they penetrate the mineral substrate contributing to rock and mineral decay, which manifests itself as bio‐weathering of rock surfaces. Given their characteristic slow and sensitive growth, SAB may also serve as bioindicators of atmospheric and/or climate change.
Morphological transformation in a freshwater Cyanobium sp. induced by grazers
Authors: Jezberová Jitka , Komárková Jaroslava
Published: May 2007

We document a remarkable morphological transformation, attributable to grazing by nanoflagellate Ochromonas sp. DS, of a phycocyanin‐rich freshwater Cyanobium sp. (10‐NR 98.2% similar 16S rRNA gene sequence to the type species Cyanobium gracile). The single cells aggregated into microcolonies (average size 40 μm) in the presence of the protist. Colonies were characterized by hundreds of tubes (spinae), 100 nm to 1 μm long and 63 ± 6 nm wide, on the surfaces of the Cyanobium cells co‐cultured with Ochromonas. Spinae production, previously unknown for the freshwater Cyanobium species, suggests that picocyanobacterial life strategies are more flexible than previously thought.
Ultrastructural and electron energy‐loss spectroscopic analysis of an extracellular filamentous matrix of an environmental bacterial isolate
Authors: Böckelmann Uta , Lünsdorf Heinrich , Szewzyk Ulrich
Published: May 2007

Strain F8, a bacterial isolate from ‘river snow’, was found to produce extracellular fibres in the form of a filamentous network. These extracellular filaments, which were previously shown to be composed of DNA, have been studied for the first time by ultrastructural and electron energy‐loss spectroscopy in the present work. ‘Whole mount’ preparations of strain F8 indicate these polymers are ultrastructurally homogeneous and form a network of elemental filaments, which have a width of 1.8–2.0 nm. When incubated at pH 3.5 with colloidal cationic ThO2 tracers they become intensely stained (electron dense), affording direct evidence that the fibres are negatively charged and thus acidic chemically. Elemental analysis of the extracellular filaments by Energy‐filtered Transmission Electron Microscopy revealed phosphorus to be the main element present and, because pretreatment of F8 cells with DNase prevented thorium labelling, the fibres must be composed of extracellular DNA (eDNA). Neither ultrathin sections nor ‘whole mount negative stain’ caused DNA release by general cell lysis. Additionally, cells infected with phages were never observed in ultrathin sections and phage particles were never detected in whole mount samples, which rules out the possibility of phages being directly involved in eDNA release.
Calcium buffering systems and calcium signaling in aged rat basal forebrain neurons
Authors: Murchison David , Griffith William H.
Published: May 2007

Disturbances of neuronal Ca2+ homeostasis are considered to be important determinants of age‐related cognitive impairment. Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and dementia. During the last several years, we have attempted to link these concepts in a rat model of ‘normal’ aging. In this review, we will describe some changes that we have observed in Ca2+ signaling of aged BF neurons and the reversal of one of these changes by dietary caloric restriction. Our evidence supports a scenario in which subtle changes in the properties of voltage‐gated Ca2+ channels result in increased Ca2+ influx during aging. This increased Ca2+, in turn, triggers an increase in rapid Ca2+ buffering in the somatic compartment of aged BF neurons. However, this nominal ‘compensation’, along with other changes in Ca2+ handling machinery (notably mitochondria) alters the Ca2+ signal with age in a way that is dependent on the magnitude of the Ca2+ load. By combining whole‐cell patch clamp electrophysiology, ratiometric Ca2+‐sensitive microfluorimetry and single‐cell reverse transcription‐polymerase chain reaction, we have determined that age‐related rapid buffering changes are present in identified cholinergic BF neurons and that these changes can be prevented by a caloric restriction dietary regimen. Because caloric restriction extends lifespan and retards the progression of age‐related dysfunction, these findings suggest that increased Ca2+ buffering in cholinergic neurons may be relevant to cognitive decline during normal aging. Importantly, calcium homeostatic mechanisms of BF cholinergic neurons are amenable to dietary interventions that could promote cognitive health during aging.
Oxidative stress and aberrant signaling in aging and cognitive decline
Authors: Dröge Wulf , Schipper Hyman M.
Published: May 2007

Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox‐sensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions. Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the insulin signaling pathway, and impaired autophagic activity has been associated with neurodegeneration. In genetic studies, impairment of insulin receptor signaling causes spectacular lifespan extension in nematodes, fruit flies, and mice. The predicted effects of age‐related oxidative stress on sirtuins and autophagic activity and the corresponding effects of antioxidants remain to be tested experimentally. However, several correlates of aging have been shown to be ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the electron transport chain, perturbations in brain iron and calcium homeostasis, and changes in plasma cysteine homeostasis may altogether represent causes and consequences of increased oxidative stress. Aging and cognitive decline thus appear to involve changes at multiple nodes within a complex regulatory network.
The importance of being subtle: small changes in calcium homeostasis control cognitive decline in normal aging
Authors: Toescu Emil C. , Verkhratsky Alexei
Published: May 2007

Aging is a complex, multifactorial process. One of the features of normal aging of the brain is a decline in cognitive functions and much experimental attention has been devoted to understanding this process. Evidence accumulated in the last decade indicates that such functional changes are not due to gross morphological alterations, but to subtle functional modification of synaptic connectivity and intracellular signalling and metabolism. Such synaptic modifications are compatible with a normal level of activity and allow the maintenance of a certain degree of functional reserve. This is in contrast to the changes in various neurodegenerative diseases, characterized by significant neuronal loss and dramatic and irreversible functional deficit. This whole special issue has been initiated with the intention of focusing on the processes of normal brain aging. In this review, we present data that shows how subtle changes in Ca2+ homeostasis or in the state of various Ca2+‐dependent processes or molecules, which occur in aging can have significant functional consequences.
Alterations in intrinsic neuronal excitability during normal aging
Authors: Disterhoft John F. , Oh M. Matthew
Published: May 2007

Normal aging subjects, including humans, have difficulty learning hippocampus‐dependent tasks. For example, at least 50% of normal aging rabbits and rats fail to meet a learning criterion in trace eyeblink conditioning. Many factors may contribute to this age‐related learning impairment. An important cause is the reduced intrinsic excitability observed in hippocampal pyramidal neurons from normal aging subjects, as reflected by an enlarged postburst afterhyperpolarization (AHP) and an increased spike‐frequency adaptation (accommodation). In this review, we will focus on the alterations in the AHP and accommodation during learning and normal aging. We propose that age‐related increases in the postburst AHP and accommodation in hippocampal pyramidal neurons play an integral role in the learning impairment observed in normal aging subjects.
Age‐dependent changes in Ca2+homeostasis in peripheral neurones: implications for changes in function
Authors: Buchholz John N. , Behringer Erik J. , Pottorf William J. , Pearce William J. , Vanterpool Conwin K.
Published: May 2007

Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability, and regulation of cell death or apoptotic pathways. The magnitude, duration and shape of stimulation‐evoked intracellular calcium ([Ca2+]i) transients are determined by a complex interplay of mechanisms that modulate stimulation‐evoked rises in [Ca2+]i that occur with normal neuronal function. Disruption of any of these mechanisms may have implications for the function and health of peripheral neurones during the aging process. This review focuses on the impact of advancing age on the overall function of peripheral adrenergic neurones and how these changes in function may be linked to age‐related changes in modulation of [Ca2+]i regulation. The data in this review suggest that normal aging in peripheral autonomic neurones is a subtle process and does not always result in dramatic deterioration in their function. We present studies that support the idea that in order to maintain cell viability peripheral neurones are able to compensate for an age‐related decline in the function of at least one of the neuronal calcium‐buffering systems, smooth endoplasmic reticulum calcium ATPases, by increased function of other calcium‐buffering systems, namely, the mitochondria and plasmalemma calcium extrusion. Increased mitochondrial calcium uptake may represent a ‘weak point’ in cellular compensation as this over time may contribute to cell death. In addition, we present more recent studies on [Ca2+]i regulation in the form of the modulation of release of calcium from smooth endoplasmic reticulum calcium stores. These studies suggest that the contribution of the release of calcium from smooth endoplasmic reticulum calcium stores is altered with age through a combination of altered ryanodine receptor levels and modulation of these receptors by neuronal nitric oxide containing neurones.
REDESCRIPTION OF PLATYCRANIELLUS ELEGANS (THERAPSIDA, CYNODONTIA) FROM THE LOWER TRIASSIC OF SOUTH AFRICA, AND THE CLADISTIC RELATIONSHIPS OF EUTHERIODONTS
Authors: ABDALA FERNANDO
Published: May 2007

Abstract:  Platycraniellus elegans is an enigmatic Triassic cynodont from South Africa that has only been briefly described previously. New preparation of the holotype and additional unpublished material allows a detailed redescription and comparison with different cynodonts. Platycraniellus elegans is recognized as a valid species of basal cynodont. The distinct suborbital angulation of the zygomatic process, previously considered as a diagnostic character in chiniquodontid cynodonts, and more recently observed in some galesaurids, is also present in P. elegans. A larger, second specimen was initially referred to P. elegans, but most recently considered to belong to Galesaurus planiceps. Close comparison of this specimen with the holotype of P. elegans and with galesaurid specimens allows a tentative allocation to G. planiceps. A cladistic analysis of 32 taxa (two gorgonopsians, seven therocephalians and 23 cynodonts) and 96 craniodental characters places P. elegans as sister taxon of Eucynodontia. Results from the analysis favour a dichotomy between (1) Cynognathia, including the sectorial‐toothed cynodonts Ecteninion, Cynognathus and the gomphodont cynodonts, and (2) Probainognathia, including most sectorial‐toothed eucynodonts (e.g. Lumkuia, Probainognathus, Chiniquodon), tritheledontids, tritylodontids and mammaliaforms. The Late Triassic sectorial‐toothed Ecteninion is the most basal member of Cynognathia, whereas the Middle Triassic Lumkuia is the basal representative of Probainognathia. Tritylodontids (Oligokyphus and Kayentatherium) are placed among Probainognathia, forming a monophyletic group with the tritheledontid Pachygenelus, whereas Brasilitherium is the sister taxon of Mammaliaformes. The cladistic analysis also indicates paraphyly for Therocephalia, with the whaitsiid Theriognathus identified as sister taxon of Cynodontia.
FIRST OCCURRENCE OF FOOTPRINTS OF LARGE THERAPSIDS FROM THE UPPER PERMIAN OF EUROPEAN RUSSIA
Authors: SURKOV MIKHAIL V. , BENTON MICHAEL J. , TWITCHETT RICHARD J. , TVERDOKHLEBOV VALENTIN P. , NEWELL ANDREW J.
Published: May 2007

Abstract:  Large footprints of terrestrial tetrapods have been found in the Cis‐Urals region of European Russia. The footprint horizon is in Late Permian (Changhsingian) deposits of the Vyatkian Gorizont (uppermost Tatarian) approximately 50 m below the local Permian/Triassic boundary. Seventeen randomly orientated footprints were excavated and are referred to the ichnospecies Brontopus giganteus. The footprints were emplaced in a reddish‐brown mudstone that was deposited from suspension beneath shallow ponded water in a floodplain environment. They were subsequently cast by the base of the overlying fine‐grained sandstone, which was deposited from a sheet‐flood event. The footprints were produced by a large therapsid, possibly a dinocephalian, but more probably a dicynodont, and represent the first ichnological record of the Therapsida from the Upper Permian of Russia.
AMMONOIDS AND THE TRIASSIC/JURASSIC BOUNDARY IN THE HIMALAYAS OF SOUTHERN TIBET
Authors: YIN JIARUN , SMITH PAUL L. , PÁLFY JÓZSEF , ENAY RAYMOND
Published: May 2007

Abstract:  The sections of Germig in the Nyalam area, southern Tibet, provide a continuous exposure of ammonoid‐bearing, uppermost Triassic and basal Jurassic strata. Eighteen species (three of them new) are described and illustrated: Choristoceras marshi Hauer, C. aff. marshi, C. cf. nobile Mojsisovics, C. nyalamense sp. nov., Eopsiloceras germigense sp. nov., Pleuroacanthites aff. biformis (Sowerby), Rhacophyllites sp., Nevadaphyllites cf. psilomorphus (Neumayr), Neophyllites sp. indet., Neophyllites cf. biptychus (Lange), Psiloceras tibeticum sp. nov., P. calliphyllum (Neumayr), Euphyllites cf. struckmanni (Neumayr), Discamphiceras pleuronotum (Canavari), Alsatites spp., Kammerkarites frigga, and K. sp. The ammonoid fauna shows a strong affinity to that of the Northern Calcareous Alps, although diversity in the Calliphyllum Zone is markedly lower. The ammonoid succession across the Triassic/Jurassic boundary is subdivided into four zones: the Rhaetian Marshi, the basal Hettangian Tibeticum, the lower Hettangian Calliphyllum, and the middle Hettangian Pleuronotum zones. It is the only known succession across the Triassic/Jurassic boundary in the Tethyan Realm that is not condensed. The Marshi and Calliphyllum zones are correlated with the same zones in the Northern Calcareous Alps. The Tibeticum Zone, a new local zone, is transitional between the Marshi and the Calliphyllum zones in that it yields both choristoceratids and psiloceratids. Its base is taken to mark the base of the Jurassic System in the eastern Tethys.
AN ALMOST COMPLETE JUVENILE SPECIMEN OF THE CHELONIID TURTLE CTENOCHELYS STENOPORUS (HAY, 1905) FROM THE UPPER CRETACEOUS NIOBRARA FORMATION OF KANSAS, USA
Authors: MATZKE ANDREAS T.
Published: May 2007

Abstract:  A new, unusually well‐preserved juvenile specimen of Ctenochelys stenoporus from the Niobrara Formation is described. The skull has come apart at its sutures and all bones of the braincase and ear region are preserved three‐dimensionally. This allows a detailed reconstruction of the important brain structures of a basal juvenile cheloniid turtle. It is compared with adult Ctenochelys specimens, and the major ontogenetic changes in the skull and postcranial skeleton are described. Furthermore, the specimen is compared with other fossil and extant cheloniids with well‐known braincases and the differences between basal and advanced cheloniids turtles are specified.
A SECOND GONDWANAN DIPLODOCID DINOSAUR FROM THE UPPER JURASSIC TENDAGURU BEDS OF TANZANIA, EAST AFRICA
Authors: REMES KRISTIAN
Published: May 2007

Abstract:  A new genus and species of diplodocid sauropod (Sauropoda, Diplodocoidea), Australodocus bohetii, is described. The type material from the Upper Jurassic (Tithonian) Tendaguru Beds of Tanzania, East Africa, consists of two successive mid‐cervical vertebrae. These vertebrae do not show the extreme elongation of the cervical vertebrae that is diagnostic for Tornieria, and, apart from proportional differences, exhibit four autapomorphic characters not seen in other diplodocids: (1) pleurocoel weakly developed; (2) ridge posterolateral to the anterior condyle strongly posteroventrally orientated; (3) triangular pneumatic cavity ventral to the prezygapophysis, enclosed by the lateral ramus of the centroprezygapophyseal lamina and an anteriorly extended prezygodiapophyseal lamina; and (4) prominent prezygapophyseal process pointed, laterally keeled and surpassing the prezygapophysis anteriorly. Australodocus bohetii is the second diplodocid known from Tendaguru, and thereby the second diplodocid known from Gondwana. This impedes the customary reference of isolated East African diplodocid material to Tornieria, which can now only be assigned to Diplodocidae indet. The find supports previously proposed vicariance models of diplodocid palaeobiogeography.
AMMONOIDS ACROSS THE PERMIAN/TRIASSIC BOUNDARY: A CLADISTIC PERSPECTIVE
Authors: McGOWAN ALISTAIR J. , SMITH ANDREW B.
Published: May 2007

Abstract:  The rapid diversification of ceratitid ammonoids during the earliest Mesozoic has been taken at face value as an example of explosive radiation following the Permian/Triassic mass extinction. However, the validity of this interpretation has never been tested within a phylogenetic framework. A total evidence cladistic analysis of Mid–Late Permian and Induan (earliest Triassic) ammonoids confirms the monophyly of the Ceratitida. Partitioned phylogenetic analysis of suture line characters vs. shell shape and ornament characters confirms the importance of suture‐line characters for resolving the higher taxonomy of ammonoids. When the cladogram is compared with the observed fossil record, the resultant tree implies that the divergence of a number of early Triassic lineages actually occurred during the latest Permian. If these range extensions are taken into account the ammonoid per‐genus extinction rate across the Permian/Triassic boundary drops from c. 85 per cent to c. 60 per cent.
THE TAXONOMIC AND PHYLOGENETIC POSITION OF THE PLESIOSAUROIDEA FROM THE LOWER JURASSIC POSIDONIA SHALE OF SOUTH‐WEST GERMANY
Authors: GROßMANN FRANZISKA
Published: May 2007

Abstract:  The two plesiosauroid species from the Posidonia shale of Holzmaden, ‘Plesiosaurus’guilelmiimperatoris and ‘Plesiosaurus’brachypterygius, do not belong to Plesiosaurus but form new monotypic genera. The new genus Hydrorion is erected for ‘P.’brachypterygius, and the genus Seeleyosaurus is re‐established for ‘P.’guilelmiimperatoris. The recently described species Plesiopterys wildii is regarded as a junior synonym of S. guilelmiimperatoris. A short phylogenetic analysis shows that S. guilelmiimperatoris and Muraenosaurus are basal elasmosaurs. H. brachypterygius, Occitanosaurus tournemirensis from France and Microcleidus homalospondylus from England form a monophyletic clade, which is the sister taxon to the Cretaceous elasmosaurs. A palaeobiogeographical comparison of plesiosaur localities in the Lower Jurassic shows distinct palaeobiogeographical zones for the Toarcian, with different plesiosaur taxa in England, Germany and France.
Prehypertension and Insulin Resistance in a Nationally Representative Adult Population
Authors: Player Marty S. , Mainous III Arch G. , Diaz Vanessa A. , Everett Charles J.
Published: May 2007

Prehypertension is associated with increased risk of cardiovascular disease and progression to hypertension. Insulin resistance (IR) is also related to cardiovascular risk. It is unknown whether individuals with prehypertension also have higher IR. The purpose of this study was to examine the association between prehypertension and IR. The National Health and Nutrition Examination Survey 1999–2002 was used to determine odds of IR by fasting insulin level >12.2 μU/mL or homeostasis model assessment (HOMA) ≥2.6 among nondiabetic adults aged 20 to 80 years across blood pressure categories. Compared with normotensives, odds of IR were over 60% higher for prehypertensive individuals by both IR measures: fasting insulin (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.12–2.48) and HOMA (OR, 1.67; 95% CI, 1.22–2.30). After stratifying by sex, IR was associated with prehypertension in only men for both IR measures. In conclusion, prehypertension is associated with higher IR in men, which may confer additional cardiovascular disease risk.
The Pathophysiologic Role of the Brain Renin‐Angiotensin System in Stroke Protection: Clinical Implications
Authors: Chrysant Steven G.
Published: May 2007

The brain possesses the same renin‐angiotensin system (RAS) as the systemic circulation. Recent experimental studies have shown that the brain RAS plays an important role in stroke and neuronal protection through its effector peptide angiotensin (Ang) II. Ang II exerts its stroke‐protective effects through stimulation of Ang II type 2 (AT2) receptors. Angiotensin receptor blockers (ARBs) exert a dual influence, which is important in their stroke protective effects. They selectively block the Ang II type 1 (AT1) receptors, decreasing local vasoconstriction, and allow free Ang II to stimulate the unoccupied AT2 receptor and increase local vasodilation, resulting in the alleviation of local brain ischemia and limiting the volume and extent of brain loss. In contrast, angiotensin‐converting enzyme (ACE) inhibitors, by decreasing the amount of Ang II production, may diminish the stroke‐protective effects of Ang II. This perhaps could be a reason for the inferior stroke‐protective effect of ACE inhibitors compared with ARBs, which has been demonstrated in several clinical trials. The evidence for this effect of ARBs compared with ACE inhibitors, however, is only indirect. Ongoing clinical trials with head‐to‐head comparisons of ARBs and ACE inhibitors will hopefully provide the needed information.
Statins and Blood Pressure: Is There an Effect or Not?
Authors: Sarafidis Pantelis A. , Kanaki Angeliki I. , Lasaridis Anastasios N.
Published: May 2007

In addition to the lipid‐lowering effects of statins, several basic and clinical studies in recent years have examined the effects of these agents on other cardiovascular parameters. Some of these studies investigated the general impact of a statin on blood pressure (BP) among various other factors, while others were specifically designed to determine this effect. Data from animal studies are conflicting but the majority of human studies in the field report a beneficial effect, and most available statin compounds are reported to lower BP levels. Recent clinical studies using ambulatory BP measurements support these findings. Although the exact actions of statins involved in this effect are unknown, several possible mechanisms can be hypothesized. This review summarizes existing data on the effect of statins on BP, aiming to give an overview of the current knowledge and to provide perspectives for future research in the field.
Cyclosporin A‐induced oxidative stress is not the consequence of an increase in mitochondrial membrane potential
Authors: van der Toorn Marco , Kauffman Henk F. , van der Deen Margaretha , Slebos Dirk‐Jan , Koëter Gerard H. , Gans Rijk O. B. , Bakker Stephan J. L.
Published: May 2007

Cyclosporin A induces closure of the mitochondrial permeability transition pore. We aimed to investigate whether this closure results in concomitant increases in mitochondrial membrane potential (ΔΨm) and the production of reactive oxygen species. Fluorescent probes were used to assess ΔΨm (JC‐1, 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐benzimidazolyl‐carbocyanine iodide), reactive oxygen species [DCF, 5‐ (and 6)‐chloromethyl‐2′,7′‐dichlorodihydrofluorescein diacetate, acetyl ester] and [Ca2+][Fluo‐3, glycine N‐[4‐[6‐[(acetyloxy)methoxy]‐2,7‐dichloro‐3‐oxo‐3H‐xanthen‐9‐yl]‐2‐[2‐[2‐[bis[2‐[(acetyloxy)methoxy]‐2‐oxyethyl]amino]‐5‐methylphenoxy]ethoxy]phenyl]‐N‐[2‐[(acetyloxy)methoxy]‐2‐oxyethyl]‐(acetyloxy)methyl ester] in human kidney cells (HK‐2 cells) and in a line of human small cell carcinoma cells (GLC4 cells), because these do not express cyclosporin A‐sensitive P‐glycoprotein. We used transfected GLC4 cells expressing P‐glycoprotein as control for GLC4 cells. NIM811 (N‐methyl‐4‐isoleucine‐cyclosporin) and PSC833 (SDZ‐PSC833) were applied as selective mitochondrial permeability transition pore and P‐glycoprotein blockers, respectively. To study the effect of cyclosporin A on mitochondrial function, we isolated mitochondria from fresh pig livers. Cyclosporin A and PSC833 induced a more than two‐fold increase in JC‐1 fluorescence in HK‐2 cells, whereas NIM811 had no effect. None of the three substances induced a significant increase in JC‐1 fluorescence in GLC4 cells. Despite this, cyclosporin A, NIM811 and PSC833 induced a 1.5‐fold increase in DCF fluorescence (P < 0.05) and a two‐fold increase in Fluo‐3 fluorescence (P < 0.05). Studies in isolated mitochondria showed that blockage of mitochondrial permeability transition pores by cyclosporin A affected neither ΔΨm, ATP synthesis, nor respiration rate. The mitochondrial permeability transition pore blockers cyclosporin A and NIM811, but also the non‐mitochondrial permeability transition pore blocker PSC833, induced comparable degrees of reactive oxygen species production and cytosolic [Ca2+]. Neither mitochondria, effects on P‐glycoprotein nor inhibition of calcineurin therefore play a role in cyclosporin A‐induced oxidative stress and disturbed Ca2+ homeostasis.
Irreversible cross‐linking of heme to the distal tryptophan of stromal ascorbate peroxidase in response to rapid inactivation by H2O2
Authors: Kitajima Sakihito , Shimaoka Taise , Kurioka Miyo , Yokota Akiho
Published: May 2007

Ascorbate peroxidase (APX) isoforms localized in the stroma and thylakoid membrane of chloroplasts play a central role in scavenging reactive oxygen species generated by photosystems. These enzymes are inactivated within minutes by H2O2 when the reducing substrate, ascorbate, is depleted. We found that, when the enzyme is inactivated by H2O2, a heme at the catalytic site of a stromal APX isoform is irreversibly cross‐linked to a tryptophan residue facing the distal cavity. Mutation of this tryptophan to phenylalanine abolished the cross‐linking and increased the half‐time for inactivation from < 10 to 62 s. In contrast with H2O2‐tolerant peroxidases, rapid formation of the cross‐link in APXs suggests that a radical in the reaction intermediate tends to be located in the distal tryptophan so that heme is easily cross‐linked to it. This is the first report of a mutation that improves the tolerance of chloroplast APXs to H2O2.
Progress for dengue virus diseases
Authors: Melino Sonia , Paci Maurizio
Published: May 2007

Transmitted by the Aedes aegypti mosquito, the dengue virus is the etiological agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, and, as such, is a significant factor in the high death rate found in most tropical and subtropical areas of the world. Dengue diseases are not only a health burden to developing countries, but pose an emerging problem worldwide. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators during dengue disease plays a key role in inducing plasma leakage, shock and hemorrhagic manifestations. Currently, there are no vaccines available against dengue virus, although several tetravalent live‐attenuated dengue vaccines are in clinical phases I or II, and prevention through vaccination has become a major priority on the agendas of the World Health Organization and of national ministries of health and military organizations. An alternative to vaccines is found in therapeutic‐based approaches. Understanding the molecular mechanisms of viral replication has led to the development of potential drugs, and new molecular viral targets for therapy are emerging. The NS3 protease domain of the NS3 protein is responsible for processing the viral polyprotein and its inhibition is one of the principal aims of pharmacological therapy. This review is an overview of the progress made against dengue virus; in particular, it examines the unique properties – structural and functional – of the NS3 protease for the treatment of dengue virus infections by the inhibition of viral polyprotein processing.
Complete reconstitution of an ATP‐binding cassette transporter LolCDE complex from separately isolated subunits
Authors: Kanamaru Kyoko , Taniguchi Naohiro , Miyamoto Shigehiko , Narita Shin‐ichiro , Tokuda Hajime
Published: May 2007

The LolCDE complex of Escherichia coli belongs to the ATP‐binding cassette transporter superfamily and mediates the detachment of lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane. The complex is composed of one copy each of membrane subunits LolC and LolE, and two copies of ATPase subunit LolD. To establish the conditions for reconstituting the LolCDE complex from separately isolated subunits, the ATPase activities of LolD and LolCDE were examined under various conditions. We found that both LolD and LolCDE were inactivated on incubation at 30 °C in a detergent solution. ATP and phospholipids protected LolCDE, but not LolD. Furthermore, phospholipids reactivated LolCDE even after its near complete inactivation. LolD was also protected from inactivation when membrane subunits and phospholipids were present together, suggesting the phospholipid‐dependent reassembly of LolCDE subunits. Indeed, the functional lipoprotein‐releasing machinery was reconstituted into proteoliposomes with E. coli phospholipids and separately purified LolC, LolD and LolE. Preincubation with phospholipids at 30 °C was essential for the reconstitution of the functional machinery from subunits. Strikingly, the lipoprotein‐releasing activity was also reconstituted from LolE and LolD without LolC, suggesting the intriguing possibility that the minimum lipoprotein‐releasing machinery can be formed from LolD and LolE. We report here the complete reconstitution of a functional ATP‐binding cassette transporter from separately purified subunits.
Cadmium‐Induced Enteropathy in Domestic Cocks: A Biochemical and Histological Study after Subchronic Exposure
Authors: Berzina Nadezhda , Markovs Jurijs , Isajevs Sergejs , Apsite Mirdza , Smirnova Galina
Published: May 2007

Abstract: The biochemical and histological sequelae resulting from a diet containing 50.20 mg cadmium/kg were studied in Lohmann brown cockerels from hatching until 30 days of age. The additional cadmium chloride (CdCl2) to the diet induced the formation of lipid peroxides, which via a chain reaction led to accumulation of malondialdehyde in intestinal mucosa. At the end of the study (after 30 days of cadmium exposure) total protein and metallothionein levels in the intestinal mucosa and the relative ileal and duodenal weight increased. Histological data show that CdCl2causes an increase in number of goblet cells and granular lymphocytes in the intestinal mucosa. Down‐regulation of the serotonin‐positive cells in the cadmium‐treated animals was observed. Growth retardation (by 27%) occurred in chicken fed the cadmium‐enriched diet for 30 days. Cadmium accumulation in the intestine was markedly higher (154 times) in the cadmium‐treated animals compared to the control group. Cadmium induced a decrease in zinc (but not copper) content in intestinal mucosa. We suggest that cadmium uptake triggers an inflammatory and secretory response in chicken small intestine.
1H‐1,2,4‐Triazol‐3‐yl‐anilines: Novel Potent Inhibitors of Vascular Endothelial Growth Factor Receptors 1 and 2
Authors: Kiselyov Alexander S. , Piatnitski Evgueni , Milligan Daniel , Ouyang Xiaohu
Published: May 2007

Novel derivatives of 1,2,4‐triazoles are described as potent ATP‐competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR‐1/2). A number of compounds display VEGFR‐2 inhibitory activity comparable to that of VatalanibTM and VandetanibTM in both homogenous time‐resolved fluorescence enzymatic and cellular assays. Several active molecules feature high intrinsic permeability (>30 × 10−5 cm/min) across Caco‐2 cell monolayer.
Natural Products Active in Aberrant c‐Kit Signaling
Authors: Henrich Curtis J. , Goncharova Ekaterina I. , Wilson Jennifer A. , Gardella Roberta S. , Johnson Tanya R. , McMahon James B. , Takada Kentaro , Bokesch Heidi R. , Gustafson Kirk R.
Published: May 2007

Development of modulators of constitutively active, kinase domain mutants of c‐Kit has proved to be very difficult. Therefore, a high‐throughput differential cytotoxicity assay was developed to screen for compounds that preferentially kill cells expressing constitutively active c‐Kit. The cells used in the assay, murine IC2 mast cells, express either the D814Y activating mutation (functionally equivalent to human D816Y) or wild type protein. This assay is robust and highly reproducible. When applied to libraries of natural product extracts (followed by assay‐guided fractionation), two differentially active compounds were identified. To assess possible mechanisms of action, the active compounds were tested for inhibitory activity against a panel of signaling enzymes (including wild type and mutant c‐Kit). Neither of the compounds significantly affected any of the 73 enzymes tested. The effects of commercially available modulators of known signaling components were also assessed using the screening assay. None of these inhibitors reproduced the differential activity seen with the natural products. Finally, both compounds were found to affect mitochondrial potential in cells expressing c‐KitD814Y. These results suggest that the newly identified natural products may provide new avenues for intervention in aberrant c‐Kit signaling pathways.