bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional effects of tau gene mutations ΔN296 and N296H
Authors: Yoshida Hirotaka , Crowther R. Anthony , Goedert Michel 
Published: March 2003

AbstractMutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome‐17 (FTDP‐17). Functionally, about half of the known mutations increase the alternative mRNA splicing of exon 10 of the tau gene, resulting in the overproduction of tau isoforms with four microtubule‐binding repeats. The other mutations reduce the ability of tau to interact with microtubules, with some mutations also increasing the propensity of tau to assemble into filaments. Here we have examined the functional effects of the recently described tau gene mutations ΔN296 and N296H. Both mutations reduced the ability of tau to promote microtubule assembly, without having a significant effect on tau filament formation. By exon trapping, they increased the splicing of exon 10. ΔN296 and N296H thus define a class of tau mutations with effects at both the RNA and the protein level.
Diabetes‐induced nitrative stress in the retina, and correction by aminoguanidine
Authors: Du Yunpeng , Smith Mark A. , Miller Casey M. , Kern T. S. 
Published: March 2003

AbstractAminoguanidine inhibits the development of retinopathy in diabetic animals, but the mechanism remains unclear. Inasmuch as aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of aminoguanidine. In vivo studies utilized retinas from experimentally diabetic rats treated or without aminoguanidine for 2 months, and in vitro studies used bovine retinal endothelial cells and a transformed retinal glial cell line (rMC‐1) incubated in 5 mm and 25 mm glucose with and without aminoguanidine	(100 µg/mL). NO was detected as nitrite and nitrate, and nitrotyrosine and iNOS were detected using immunochemical methods. Retinal homogenates from diabetic animals had greater than normal levels of NO and iNOS (p < 0.05), and nitrotyrosine was greater than normal, especially in one band immunoprecipitated from retinal homogenates. Oral aminoguanidine significantly inhibited all of these increases. Nitrotyrosine was detected immunohistochemically only in the retinal vasculature of non‐diabetic and diabetic animals. Retinal endothelial and rMC‐1 cells cultured in high glucose increased NO and NT, and aminoguanidine inhibited both increases in rMC‐1 cells, but only NT in endothelial cells. Hyperglycemia increases NO production in retinal cells, and aminoguanidine can inhibit this abnormality. Inhibition of diabetic retinopathy by aminoguanidine might be mediated in part by inhibition of sequelae of NO production.
Participation of protease‐activated receptor‐1 in thrombin‐induced microglial activation
Authors: Suo Zhiming , Wu Min , Ameenuddin Syed , Anderson Heidi E. , Zoloty Jamie E. , Citron Bruce A. , Andrade‐Gordon Patricia , Festoff Barry W. 
Published: March 2003

AbstractActivation of microglia, the resident macrophages in the CNS, plays a significant role in neuronal death or degeneration in a broad spectrum of CNS disorders. Recent studies indicate that nanomolar concentrations of the serine protease, thrombin, can activate microglia in culture. However, in contrast to other neural cells responsive to thrombin, the participation of novel protease‐activated receptors (PARs), such as the prototypic thrombin receptor PAR1, in thrombin‐induced microglial activation was cast in doubt. In this report, by utilizing primary microglial cultures from PAR1 knockout (PAR1–/–) mice, application of the PAR1 active peptide TRAP‐6 (SFLLRN) in comparison to a scrambled peptide (LFLNR), we have unambiguously demonstrated that murine microglia constitutively express PAR1 mRNA that is translated into fully functional protein. Activation of the microglial PAR1 induces a rapid cytosolic free [Ca2+]i increase and transient activation of both p38 and p44/42 mitogen‐activated protein kinases. Moreover, although in part, this PAR1 activation directly contributes to thrombin‐induced microglial proliferation. Furthermore, although not directly inducing tumor necrosis factor‐α (TNF‐α) release, PAR1 activation up‐regulates microglial CD40 expression and potentiates CD40 ligand‐induced TNF‐α production, thus indirectly contributing to microglial activation. Taken together, these results demonstrate an essential role of PAR1 in thrombin‐induced microglial activation. In addition, strategies aimed at blocking thrombin signaling through PAR1 may be therapeutically valuable for diseases associated with cerebral vascular damage and significant inflammation with microglial activation.
Na,K‐ATPase α3 subunit in the goldfish retina during optic nerve regeneration
Authors: Liu Z. W. , Matsukawa T. , Arai K. , Devadas M. , Nakashima H. , Tanaka M. , Mawatari K. , Kato S. 
Published: March 2003

AbstractThe goldfish optic nerve can regenerate after injury. To understand the molecular mechanism of optic nerve regrowth, we identified genes whose expression is specifically up‐regulated during the early stage of optic nerve regeneration. A cDNA library constructed from goldfish retina 5 days after transection was screened by differential hybridization with cDNA probes derived from axotomized or normal retina. Of six cDNA clones isolated, one clone was identified as the␣Na,K‐ATPase catalytic subunit α3 isoform by high‐ sequence homology. In northern hybridization, the expression level of the mRNA was significantly increased at 2 days and peaked at 5–10 days, and then gradually decreased and returned to control level by 45 days after optic nerve transection. Both in situ hybridization and immunohistochemical staining have revealed the location of this transient retinal change after optic nerve transection. The increased expression was observed only in the ganglion cell layer and optic nerve fiber layer at 5–20 days after optic nerve transection. In an explant culture system, neurite outgrowth from the retina 7 days after optic nerve transection was spontaneously promoted. A low concentration of ouabain (50–100 nm) completely blocked the spontaneous neurite outgrowth from the lesioned retina. Together, these data indicate that up‐regulation of the Na,K‐ATPase α3 subunit is involved in the regrowth of ganglion cell axons after axotomy.
The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity
Authors: Fischer Frauke , Molinari Maurizio , Bodendorf Ursula , Paganetti Paolo 
Published: March 2003

Abstractβ‐Site APP‐cleaving enzyme (BACE) initiates the processing of the amyloid precursor protein (APP) leading to the generation of β‐amyloid, the main component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a type I transmembrane aspartic protease responsible for the β‐secretase cleavage of APP producing a soluble form of the ectodomain (sAPPβ) and the membrane‐bound, carboxy‐terminal intermediates C99 and C89. BACE maturation involves cysteine bridge formation, N‐glycosylation and propeptide removal. We investigated variants of BACE in which the disulphide bonds of the catalytic domain spanning between Cys216/Cys420, Cys278/Cys443 and Cys330/Cys380 were removed by mutagenesis. When transfected in cultured cells, these mutants showed impaired maturation. Nevertheless, a fraction of mutated protein retained both the competence to mature as well as the activity to process APP. For the generation of a functional enzyme the conserved Cys330/Cys380 bond was the most critical, whereas the two bonds between Cys216/Cys420 and Cys278/Cys443, which are typical for the membrane‐bound BACE, appeared to be less important.
Phylogeography of the ectomycorrhizal Pisolithus species as inferred from nuclear ribosomal DNA ITS sequences
Authors: Martin Francis , Díez Jesús , Dell Bernard , Delaruelle Christine 
Published: March 2003

Summary

The fungal genus Pisolithus is cosmopolitan in warm temperate regions and forms ectomycorrhizal associations with a wide range of woody plants. To delimit phylogenetic Pisolithus species and identify their geographical distribution, 102 collections were made worldwide and their rDNA internal transcribed spacer (ITS) was sequenced.
Phylogenetic analyses of these sequences, together with 46 additional GenBank accessions, identified 11 species.
A strong phylogeographical pattern was observed related to the native geographical origin of the host plants. In the Holarctic, P. tinctorius was widely distributed, associated with Pinus and Quercus. It has been co‐introduced with pines to other biogeographical regions. Several Pisolithus lineages, including P. aurantioscabrosus, occurred in restricted biogeographical regions associated with endemic plants, such as Afzelia in eastern Africa. Pisolithus albus, P. marmoratus and P. microcarpus were associated with Australasian hosts (Eucalyptus, Acacia) and were distributed with their hosts worldwide. By contrast, two additional unnamed species were restricted to Australia.
The present study shows that evolutionary lineages within Pisolithus are related to the biogeographical origin of the hosts. In addition, regional floras and endemic plants could act as hosts of endemic species of Pisolithus.
Myco‐photobiontal selection in a Mediterranean cryptogam community with Fulgensia fulgida
Authors: Beck A. , Kasalicky T. , Rambold G. 
Published: March 2003

Summary

To examine the mode of dispersal and photobiont selectivity of Fulgensia fulgida we investigated the photobionts associated with the lichens of a community related to the Toninio–Psoretum decipientis association.
Photobionts and mycobionts were analysed using morphological (light microscopy) and molecular (internal transcribed spacer (ITS) and partial large subunit (LSU) nuclear ribosomal DNA sequencing) techniques.
The thalli of the mycobiont of F. fulgida, which were identical in their ITS and partial LSU‐sequence, contained two strains of Trebouxia asymmetrica, one of them also present in a thallus of Toninia sedifolia. Other co‐occurring lichens, namely Squamarina lentigera, Catapyrenium michelii and Collema cristatum, were shown to have Asterochloris irregularis, Myrmecia and Nostoc as photobionts.
It is suggested that F. fulgida is selective in its photobiont choice, that dispersal of the lichen has occurred by way of ascospores and subsequent independent relichenization events and that F. fulgida and T. sedifolia share the same photobiont pool. The results also suggest possible mechanisms of relichenization and strategies for future research on the selectivity of lichen bionts.
Identification and transmission of Piper yellow mottle virus and Cucumber mosaic virus infecting black pepper (Piper nigrum) in Sri Lanka
Authors: De Silva D. P. P. , Jones P. , Shaw M. W. 
Published: March 2003

Sri Lankan black pepper with symptoms of yellow mottle disease contained a mixture of viruses: Piper yellow mottle virus (PYMV) particles (30 × 130 nm), Cucumber mosaic virus (CMV, 30 nm diameter isometric particles), and unidentified, isometric virus‐like particles (30 nm diameter). An effective purification procedure is described for PYMV. Immunosorbent and conventional electron microscopy successfully detected badnavirus particles only when at least partially purified extracts were used. PYMV was confirmed as the cause of the disease, with the other two viruses apparently playing no part in producing symptoms. PYMV was transmitted by grafting, by the insect vectors citrus mealy bug (Planococcus citri) and black pepper lace bug (Diconocoris distanti), but not by mechanical inoculation or through seeds. The CMV isolate was transmitted to indicator plants by mechanical inoculation and by the vector Aphis gossypii, but not by Myzus persicae; but neither mechanical nor insect transmission of CMV to black pepper was successful. A sensitive polymerase chain reaction assay was developed to detect PYMV in black pepper.
Metamorphism at a late Mesozoic accretionary margin: a study from the Coast Belt of the North American Cordillera
Authors: Mezger J. E. , Chacko T. , Erdmer P. 
Published: March 2003

AbstractThe late Mesozoic and Cenozoic metamorphic evolution of the western North American continental margin is recorded in a belt of homogeneous metapelitic rocks, the Kluane metamorphic assemblage (KMA), in the northern Coast Belt of Yukon Territory. A record of Late Cretaceous medium‐pressure and ‐temperature (c. 7 kbar, 500 °C) metamorphism, M1, is preserved in Ca‐rich garnet and Na‐rich plagioclase cores in rocks that were little affected by later events. M1 was synchronous with mylonitization and is attributed to accretion of the KMA to the ancient continental margin. Isothermal decompression during rapid uplift was followed by early Eocene emplacement of the Ruby Range Batholith (RRB), part of a magmatic arc produced by subduction of the Kula plate. The intrusion of the RRB led to a contact metamorphic overprint, M2, producing a 5–6 km wide aureole in which the grade ranges from subgarnet zone to garnet–cordierite–K‐feldspar zone. Pressure and temperature estimates for M2, calculated from mineral equilibria, are 3.5–4.5 kbar and 530–720 °C, generally consistent with the stability limits of the observed mineral assemblages. Comparison of mineral assemblages and P–T conditions in the KMA with those in the Mclaren Glacier metamorphic belt in Alaska does not support the correlation of the two metamorphic sequences. This weakens the hypothesis proposing 400 km of dextral slip along the Denali fault zone.
Cretaceous evolution of a metamorphic core complex, the Veporic unit, Western Carpathians (Slovakia): P–T conditions and in situ40Ar/39Ar UV laser probe dating of metapelites
Authors: Janák M. , Plašienka D. , Frey M. , Cosca M. , Schmidt S. TH. , Lupták B. , Méres Š. 
Published: March 2003

AbstractAlpine metamorphism, related to the development of a metamorphic core complex during Cretaceous orogenic events, has been recognized in the Veporic unit, Western Carpathians (Slovakia). Three metamorphic zones have been distinguished in the metapelites: 1, chloritoid + chlorite + garnet; 2, garnet + staurolite + chlorite; 3, staurolite + biotite + kyanite. The isograds separating the metamorphic zones have been modelled by discontinuous reactions in the system K2O–FeO–MgO–Al2O3–SiO2–H2O (KFMASH). The isograds are roughly parallel to the north‐east‐dipping foliation related to extensional updoming along low‐angle normal faults. Thermobarometric data document increasing P–T conditions from c. 500 °C and 7–8 kbar to c. 620 °C and 9–10 kbar, reflecting a coherent metamorphic field gradient from greenschist to middle amphibolite facies. 40Ar/39Ar data obtained by high spatial resolution in situ ultraviolet (UV) laser ablation of white micas from the rock slabs constrain the timing of cooling and exhumation in the Late Cretaceous. Mean dates are between 77 and 72 Ma; however, individual white mica grains record a range of apparent 40Ar/39Ar ages indicating that cooling below the blocking temperature for argon diffusion was not instantaneous. The reconstructed metamorphic P–T–t path is ‘clockwise’, reflecting post‐burial decompression and cooling during a single Alpine orogenic cycle. The presented data suggest that the Veporic unit evolved as a metamorphic core complex during the Cretaceous growth of the Western Carpathian orogenic wedge. Metamorphism was related to collisional crustal shortening and stacking, following closure of the Meliata Ocean. Exhumation was accomplished by synorogenic (orogen‐parallel) extension and unroofing in an overall compressive regime.
Interaction of metamorphism, deformation and exhumation in large convergent orogens
Authors: Jamieson R. A. , Beaumont C. , Nguyen M. H. , Lee B. 
Published: March 2003

AbstractCoupled thermal‐mechanical models are used to investigate interactions between metamorphism, deformation and exhumation in large convergent orogens, and the implications of coupling and feedback between these processes for observed structural and metamorphic styles. The models involve subduction of suborogenic mantle lithosphere, large amounts of convergence (≥ 450 km) at 1 cm yr−1, and a slope‐dependent erosion rate. The model crust is layered with respect to thermal and rheological properties — the upper crust (0–20 km) follows a wet quartzite flow law, with heat production of 2.0 μW m−3, and the lower crust (20–35 km) follows a modified dry diabase flow law, with heat production of 0.75 μW m−3. After 45 Myr, the model orogens develop crustal thicknesses of the order of 60 km, with lower crustal temperatures in excess of 700 °C. In some models, an additional increment of weakening is introduced so that the effective viscosity decreases to 1019 Pa.s at 700 °C in the upper crust and 900 °C in the lower crust. In these models, a narrow zone of outward channel flow develops at the base of the weak upper crustal layer where T≥600 °C. The channel flow zone is characterised by a reversal in velocity direction on the pro‐side of the system, and is driven by a depth‐dependent pressure gradient that is facilitated by the development of a temperature‐dependent low viscosity horizon in the mid‐crust. Different exhumation styles produce contrasting effects on models with channel flow zones. Post‐convergent crustal extension leads to thinning in the orogenic core and a corresponding zone of shortening and thrust‐related exhumation on the flanks. Velocities in the pro‐side channel flow zone are enhanced but the channel itself is not exhumed. In contrast, exhumation resulting from erosion that is focused on the pro‐side flank of the plateau leads to ‘ductile extrusion’ of the channel flow zone. The exhumed channel displays apparent normal‐sense offset at its upper boundary, reverse‐sense offset at its lower boundary, and an ‘inverted’ metamorphic sequence across the zone. The different styles of exhumation produce contrasting peak grade profiles across the model surfaces. However, P–T–t paths in both cases are loops where Pmax precedes Tmax, typical of regional metamorphism; individual paths are not diagnostic of either the thickening or the exhumation mechanism. Possible natural examples of the channel flow zones produced in these models include the Main Central Thrust zone of the Himalayas and the Muskoka domain of the western Grenville orogen.
Quality of web‐based medical information on stable COPD: comparison of non‐commercial and commercial websites
Authors: Kunst Heinke , Khan Khalid S. 
Published: March 2003

AbstractThe Internet provides an easy and accessible way to deliver medical information about the management of various diseases, both to practitioners and to their patients. As there is no control over who posts information on the Web, there is a risk that the interests of the web producer may bias the quality of information. The quality of medical information on the management of chronic obstructive pulmonary disease (COPD) on the Internet was evaluated, comparing non‐commercial and commercial websites. An internet search was conducted to locate relevant websites using a metasearch engine. The quality of websites was scored on a scale of 0–10, based on three items about the credibility of the site and seven items about the accuracy of the information provided by the site. Quality differences between commercial and non‐commercial websites were explored. The search revealed 23 relevant websites (12 non‐commercial and 11 commercial). The overall quality of non‐commercial websites was better than that of commercial websites (median score 7 vs. 4, p= 0.01). Compared to commercial sites, non‐commercial websites more often provided information about cessation of smoking (100% vs. 64%, p= 0.03), preventative influenza vaccinations (42% vs. 9%, p= 0.07) and use of long‐term oxygen therapy (92% vs. 45%, p= 0.02). Among websites providing information on COPD, commercial sites were much more likely to be of poorer quality compared to sites of non‐commercial organizations. In particular, commercial sites do not provide information about simple preventative treatments. There is a need to be vigilant about the quality of health information about COPD on the Internet.
Electroantennogram and behavioural responses of the malaria vector Anopheles gambiae to human‐specific sweat components
Authors: Costantini C. , Birkett M. A. , Gibson G. , Ziesmann J. , Sagnon N'F. , Mohammed H. A. , Coluzzi M. , Pickett J. A. 
Published: March 2003

Abstract. Afrotropical malaria vectors of the Anopheles gambiae complex (Diptera: Culicidae), particularly An. gambiae sensu stricto, are attracted mainly to human hosts. A major source of human volatile emissions is sweat, from which key human‐specific components are the carboxylic acids (E)‐ and (Z)‐3‐methyl‐2‐hexenoic acid and 7‐octenoic acid. Electrophysiological studies on the antennae of An. gambiae s.s. showed selective sensitivity to these compounds, with a threshold at 10−6 g comparable to that of known olfactory stimulants 1‐octen‐3‐ol, p‐cresol, isovaleric acid, and lower than threshold sensitivity to l‐lactic acid and the synthetic mosquito repellent N,N‐diethyltoluamide (DEET). A combination of the acids released at concentrations > 10−5 g in wind tunnel bioassays significantly reduced the response to CO2, the major attractant released by human hosts, for strains of An. gambiae s.s. originating from East and West Africa.Field trials with odour‐baited entry traps (OBETs) in Burkina Faso showed that 7‐octenoic acid significantly increased (by 1.7‐fold) the catch of females of An. gambiae sensu lato (comprising two sibling species: An. arabiensis Patton and An. gambiae s.s.) in OBETs baited with CO2, whereas combinations of the acids significantly reduced the catch in CO2‐baited traps (by 2.1‐fold) and in whole human odour‐baited traps (by 1.5‐fold). The pure (E) and (Z) geometric isomers of 3‐methyl‐2‐hexenoic acid gave comparable results to the (E/Z) isomer mixture. These results provide the first experimental evidence that human‐specific compounds affect the behaviour of highly anthropophilic An. gambiae s.l. mosquitoes. The compounds appear to inhibit the ‘upwind flight’ response to known long‐range attractants, and may serve either to ‘mask’ the attractants present or, more probably, to ‘arrest’ upwind flight when mosquitoes arrive at a host under natural conditions. In the final approach to hosts, vectors are known to reduce their flight speed and increase their turning rate, to avoid overshooting the source. In our experimental apparatus, these changes in flight behaviour would reduce the number of mosquitoes entering the ports of the collection devices.
Phylogeny of the Strepsiptera based on morphological data of the first instar larvae
Authors: Pohl Hans 
Published: March 2003

This investigation was the first cladistic analysis using morphological data of first instar larvae of Strepsiptera. The analysis of representatives of nearly all known families of Strepsiptera supports the division of Strepsiptera into Mengenillidia and Stylopidia. Corioxenidae and Elenchidae are placed at the base of Stylopidia. Halictophagidae is the sister group to Xeninae + Myrmecolacidae + Stylopinae. Xeninae is placed as the sister group to Myrmecolacidae + Stylopinae. Stylopidae are paraphyletic. Thus, Xenidae stat. n. is re‐established. A sister‐group relationship between Myrmecolacidae and Elenchidae is not supported on characters of first instar larvae.