bluuebunny/crossref_metadata_2025 huggingface dataset:
Diuretic hormone 44 receptor in Malpighian tubules of the mosquito Aedes aegypti: evidence for transcriptional regulation paralleling urination
Authors: Jagge C. L. , Pietrantonio P. V.
Published: July 2008

In the mosquito Aedes aegypti (L.), the molecular endocrine mechanisms underlying rapid water elimination upon eclosion and blood feeding are not fully understood. The genome contains a single predicted diuretic hormone 44 (DH44) gene, but two DH44 receptor genes. The identity of the DH44 receptor(s) in the Malpighian tubule is unknown in any mosquito species. We show that VectorBase gene ID AAEL008292 encodes the DH44 receptor (GPRDIH1) most highly expressed in Malpighian tubules. Sequence analysis and transcript localization indicate that AaegGPRDIH1 is the co‐orthologue of the Drosophila melanogaster DH44 receptor (CG12370‐PA). Time‐course quantitative PCR analysis of Malpighian tubule cDNA revealed AaegGPRDIH1 expression changes paralleling periods of excretion. This suggests that target tissue receptor biology is linked to the known periods of release of diuretic hormones from the nervous system pointing to a common up‐stream regulatory mechanism.
Spatial variation of wetland woods in the latitudinal transition to arid regions: a multiscale approach
Authors: Rodríguez‐González Patricia María , Ferreira Maria Teresa , Albuquerque António , Santo Dalila Espirito , Rego Pablo Ramil
Published: July 2008

Aim  In order to investigate the occurrence of wetland woods in the latitudinal transition to arid regions in south‐western Europe, we studied species patterns (richness and abundance), examined floristic differences between woods along the latitudinal gradient, and determined the relative influence of the underlying environmental drivers of plant variation at various scales.

Location  The Atlantic coastal belt of the Iberian Peninsula along the entire latitudinal gradient (44–38° N).

Methods  Large‐scale surveys were carried out in search of woods located in flats or depressions with prolonged waterlogging. Stands were selected for study when they displayed a continuous tree structure and little sign of human disturbance. Sampling included plant inventories in 114 plots, in which presence and abundance cover were recorded for all vascular and bryophyte species. Both diversity and composition were used to investigate plant species patterns. Gamma and alpha diversity (species richness) values were used to compare Ibero‐Atlantic wetland woods with other European woods. Species richness was modelled as a function of environmental variation at regional and finer scales (landscape and local scale), using linear mixed‐effects models and model selection based on the Akaike information criterion. Hierarchical clustering and ordination using perennial species were used to detect floristic differences between sites. Partial canonical correspondence analyses were performed to determine the relative importance of each set of environmental drivers in structuring the vegetation trends at regional and finer scales.

Results  A significant proportion of wetland woods occurred in the transition to the Mediterranean region. Ibero‐Atlantic wetland woods displayed low gamma and alpha diversity compared with other woods. Species richness was strongly influenced by finer‐scale variables, in particular distance to rivers, whereas regional variables were less influential. Based on tree dominance, the classification revealed five vegetation types, but the majority of stands (86%) were included in woods dominated by Salix atrocinerea Brot. and Alnus glutinosa (L.) Gaertner. Species abundances were correlated with both regional and finer‐scale hydrological variables, which explained 37.5% of the variation, 11.9% of which corresponded to regional and 18.5% to finer‐scale environmental descriptors.

Main conclusions  True wetland woods persist in the transition to arid regions of south‐western Europe. The latitudinal gradient influences the spatial variation of species, but local hydrological variables were found to play a significant role in both diversity and compositional patterns.
Cyclic habitat displacements during Pleistocene glaciations have induced independent evolution of Tasimia palpata populations (Trichoptera: Tasimiidae) in isolated subtropical rain forest patches
Authors: Múrria C. , Hughes J. M.
Published: July 2008

Aim  Mechanisms generating biodiversity and endemism are influenced by both historical and ecological patterns, and the relative roles of history vs. ecological interactions are still being debated. The phylogeography of one rain forest‐restricted caddisfly species, Tasimia palpata, thought to have good dispersal abilities, is used to address questions about shifts of highland rain forest habitat during Pleistocene glaciations and about their consequences for haplotype composition and distribution.

Location  Tasimia palpata occurs in highland subtropical rain forest patches, which are separated from one another by lowland dry bush, in south‐eastern Queensland, Australia.

Methods  We sequenced 375 base pairs of the mitochondrial cytochrome oxidase I gene from 169 individuals (20 populations) of T. palpata, mainly from three fragmented subtropical rain forest blocks, revealing 46 haplotypes. Analysis of molecular variance (amova), genetic divergence between populations, nested clade analyses and tests based on coalescent theory were used to analyse phylogeographical relationships among T. palpata populations.

Results  amova indicates spatial genetic structure between isolated subtropical rain forest patches, with an isolation‐by‐distance effect. Tests based on coalescent theory suggest a repeated process of population reductions and divergence between isolated rain forests during Pleistocene glaciations as a consequence of habitat constrictions followed by population expansions during interglacial periods when subtropical rain forest expanded. In addition, these results suggest that, prior to the Pleistocene, rain forest and T. palpata had more widespread distributions in this region.

Main conclusions  Historical rain forest expansion and contraction during the Pleistocene resulted in changes in demography and genetic diversity of T. palpata, as well as in an increase in genetic divergence between populations from different patches of subtropical rain forest. Despite the fact that this caddisfly species was isolated in separate highland rain forest patches at various times during the Pleistocene, there is no evidence of allopatric speciation during the Quaternary, which contrasts with other examples of endemism and high diversity in rain forest highlands.
A macroevolutionary mosaic: episodic host‐switching, geographical colonization and diversification in complex host–parasite systems
Authors: Hoberg Eric P. , Brooks Daniel R.
Published: July 2008

Aim To integrate ecological fitting, the oscillation hypothesis and the taxon pulse hypothesis into a coherent null model for the evolution of complex host–parasite associations.

Location Global.

Methods This paper reviews and synthesizes literature that focuses on phylogenetic analyses and reciprocal mapping of a model system of hosts and their parasites to determine patterns of host–parasite associations and geographical distributions through time.

Results Host‐switching and geographical dispersal of parasites are common phenomena, occurring on many temporal and spatial scales. Diversification involving both co‐evolution and colonization explains complex host–parasite associations. Across the expanse of Earth history, the major radiations in host–parasite assemblages have been preceded by ecological disruption, ecological breakdown and host‐switching in a context that can be defined by the concept of ecological fitting. This cyclical process sets the stage for co‐diversification during periods of relative stability, punctuated by host‐switching during episodes of regional to global environmental disruption and climatological change.

Main conclusions Most observed host–parasite associations can be explained by an historical interaction between ecological fitting, oscillation (episodes of increasing host range alternating with isolation on particular hosts) and taxon pulses (cyclical episodes of expansion and isolation in geographical range). Major episodes of environmental change appear to be the main drivers for both the persistence and diversification of host–parasite systems, creating opportunities for host‐switching during periods of geographical expansion and allowing for co‐evolution and co‐speciation during periods of geographical isolation.
Recruitment filters in a perennial grassland: the interactive roles of fire, competitors, moisture and seed availability
Authors: Zimmermann Julia , Higgins Steven I. , Grimm Volker , Hoffmann John , Münkemüller Tamara , Linstädter Anja
Published: July 2008

Demographic processes, particularly the recruitment of seedlings, are critical to the long‐term survival and re‐establishment of plant populations. In many perennial grasslands successful recruitment is a rare event that requires the simultaneous favourable alignment of several environmental variables.

Although a few empirical studies have examined demographic processes in perennial grasslands, most of these studies investigate the impact of only one or two environmental factors in isolation. Those studies would lead us to expect that seed availability, irrigation and burning, enhance recruitment rates whereas the presence of established competitors substantially lowers recruitment rates. But how these factors, or recruitment filters, act in concert and how they influence the different components of the recruitment process such as seedling emergence, survival and growth is not understood.

For this reason we explore the relative and combined influence of four factors – seed availability, irrigation, competition by the established vegetation, and fire – on the recruitment process of a perennial grass (Stipagrostis uniplumis) in semi‐arid savanna. We used a full factorial experiment to determine how these four factors influence emergence, growth, survival and flowering of seedlings.

Our results show that all of the factors affected some stage of the recruitment process but not all significant effects contributed to enhancing the final number of recruits.

We found enhanced seed availability to significantly enhance rates of seedling emergence but to play no further role in the recruitment process. Competition by the established vegetation exerted a strong negative effect on every step of the recruitment process. Irrigation had a minor effect on recruitment. It enhanced rates of flowering and survival during the growing season but the effect of the stimulus was short‐lived and did not influence later stages of the recruitment process.

In contradiction to existing theory, seedling recruitment does therefore not seem to be limited to above average rainfall years. Fire acted similarly to the removal of competitors; that is, it positively affected seedling emergence, growth, flowering and survival.

Synthesis. We conclude that recruitment is not limited to above average rainfall years but triggered by events that open up the grass canopy and reduce the abundance of competitors. Specifically it appears that periodic fires enable the recruitment of new individuals into the population. This study shows that fire can play an important positive role in individual turnover of semi‐arid perennial grass populations.
Offering choices to people with intellectual disabilities: an interactional study
Authors: Antaki C. , Finlay W. , Walton C. , Pate L.
Published: July 2008

Background  At the level of policy recommendation, it is agreed that people with intellectual impairments ought to be given opportunities to make choices in their lives; indeed, in the UK, the Mental Capacity Act of 2005 enshrines such a right in law. However, at the level of practice, there is a dearth of evidence as to how choices are actually offered in everyday situations, which must hinder recommendations to change.

Method  This qualitative interactional study, based on video recordings in British residential homes, combines ethnography with the fine‐grained methods of Conversation Analysis.

Results  We identify six conversational practices that staff use to offer choices to residents with intellectual disabilities.

Conclusions  We describe the unwanted consequences of some of these practices, and how the institutional imperative to solicit clear and decisive choice may sometimes succeed only in producing the opposite.
Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation
Authors: Sarafoff N. , Ndrepepa G. , Mehilli J. , Dörrler K. , Schulz S. , Iijima R. , Byrne R. , Schömig A. , Kastrati A.
Published: July 2008

Objectives.  Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug‐eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC.

Methods.  We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent‐related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke.

Results.  During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan–Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29–1.28; P = 0.19]. At 2 years of follow‐up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan–Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48–1.21; P = 0.25). Two‐year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34).

Conclusions.  In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.
Direct Inhibitory Effect of Glucocorticoids on Corticotrophin‐Releasing Hormone Gene Expression in Neurones of the Paraventricular Nucleus in Rat Hypothalamic Organotypic Cultures
Authors: Bali B. , Ferenczi S. , Kovács K. J.
Published: July 2008

Corticotrophin‐releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1 μm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24 h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin‐stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin‐induced CRH mRNA expression in explant cultures of the rat hypothalamus.
Development of an Immortalised, Post‐Pubertal Gonadotrophon‐Releasing Hormone Neuronal Cell Line
Authors: Wolfe A. , Ng Y. , Divall S. A. , Singh S. P. , Radovick S.
Published: July 2008

Gonadotrophin‐releasing hormone (GnRH) is important in reproduction, although some of the mechanisms for its synthesis and release remain elusive. Progress in understanding the GnRH neurone has been hampered by the limited number and diffuse distribution of the neurone in the mammalian brain. Several stable GnRH‐expressing cell lines have been developed using in vivo expression of the simian virus 40 T Antigen (TAg), and they have been helpful for the study of gene expression and neuronal function. However, expression of an immortalising gene may interfere with normal cellular function. We developed a novel GnRH‐secreting cell line transgenic mouse model suitable for targeted transformation in post‐pubertal mice using a tetracycline‐regulated TAg transgene. This clonal cell line, GRT, expresses neuronal markers and GnRH. GRT cells grown in medium containing tetracycline‐free serum express increasing mRNA levels of GnRH associated with declining levels of TAg expression. The novelty and ultimately the usefulness of this cell line is that TAg expression, which could affect the GnRH neuronal phenotype, can be regulated by tetracycline.
Expression of Neurotensin and its Receptors in Pituitary Adenomas
Authors: Giorgi R. R. , Chile T. , Bello A. R. , Reyes R. , Fortes M. A. H. Z. , Machado M. C. , Cescato V. A. , Musolino N. R. , Bronstein M. D. , Giannella‐Neto D. , Corrêa‐Giannella M. L.
Published: July 2008

The neurotensin (NT) produced in the hypothalamus and in pituitary gonadotrophs and thyrotrophs participates in neuroendocrine regulation. Recently, the involvement of this peptide in normal and neoplastic cell proliferation has been postulated. In the present study, we evaluated the expression of NT and its receptors (NTR1, 2 and 3) in a series of 50 pituitary adenomas [11 growth hormone (GH)‐, eight prolactin (PRL)‐, four adrenocorticotrophic hormone (ACTH)‐ and 27 nonfunctioning adenomas]. NT mRNA expression was significantly higher in functioning compared to nonfunctioning adenomas and with normal pituitary. Nonfunctioning pituitary adenomas showed lower expression of NT mRNA than normal pituitary. In the immunohistochemical study of functioning adenomas, NT was colocalised with GH, PRL and ACTH secreting cells. In nonfunctioning adenomas, the NT immunoreactivity intensity was variable among the samples. NTR3 mRNA expression was observed in all examined samples and was higher in the adenomas, both functioning and nonfunctioning, compared to normal pituitary. By contrast, NTR1 and NTR2 mRNA were not detected in either pituitary adenomas or normal tissue. The higher expression of NTR3, as well as the expression of NT by tumoural corticotrophs, lactotrophs and somatotrophs, which are cells types that do not express this peptide in the normal pituitary, suggests that NT autocrine and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with the tumourigenesis of functioning adenomas.
A prospective study of patients absconding from a general hospital psychiatry unit in a developing country
Authors: KHISTY N. , RAVAL N. , DHADPHALE M. , KALE K. , JAVADEKAR A.
Published: July 2008

Characteristics of patients absconding from an open psychiatry ward in a developing country may be different from both those in developed countries and a mental hospital setting. The aim of this paper is to study the incidence and characteristics of patients absconding from an open psychiatric ward in a general hospital‐based psychiatric unit in India. We studied patients consecutively admitted to an open psychiatric ward over a 2‐month period. We compared those who absconded with those who did not. Out of 231 patients admitted, 33 absconded. Among those who absconded, 15 had bipolar disorder, 11 had schizophrenia and five had substance‐related disorders. Nine had indicated their intention to do so at admission. Ten patients had absconded by the second day. The treatment cost was the likely influencing factor for seven patients who absconded after deemed fit for discharge on clinical grounds. Only 10 patients were readmitted to the hospital within 2 weeks of absconding. The risk of absconding is highest in the early days following. Absconding patients did not differ significantly from others in many socio‐demographic and clinical features. Treatment costs are an important consideration in India.
An examination of the services provided by Psychiatric Consultation Liaison Nurses in a general hospital
Authors: JOHNSTON M. L. , COWMAN S.
Published: July 2008

The political, professional and economic context in which mental health care is delivered has witnessed significant changes in recent times. The movement of psychiatric patients from institutions to community settings has seen the emphasis of the loci of care delivery shifting with increasing numbers presenting to general hospitals. The speciality of the Psychiatric Consultation Liaison Nurse (PCLN) has emerged as a bridge between mental health and general hospital services. A descriptive, non‐experimental research approach was employed to establish patient profiles and to provide an overview of the depth of service provision. This design was selected as the most appropriate because of the limited information on the PCLN in an Irish setting and secondly, as the study was limited to one rural geographical location. A questionnaire was utilized to collate the details of patients who had received a mental health assessment. The findings presented here are the profiles of patients assessed by the PCLN during the 3‐month study period. The results add further credence to the existing evaluative studies in presenting the characteristics of patients within the Irish context and further contribute to the unique body of evidence that defines the mental health nurse in an advancing role.
Carbon metabolism of Listeria monocytogenes growing inside macrophages
Authors: Eylert Eva , Schär Jennifer , Mertins Sonja , Stoll Regina , Bacher Adelbert , Goebel Werner , Eisenreich Wolfgang
Published: July 2008

The intracellular metabolism of Listeria monocytogenes was studied by 13C‐isotopologue profiling using murine J774A.1 macrophages as host cells. Six hours after infection, bacteria were separated from the macrophages and hydrolyzed. Amino acids were converted into tert‐butyl‐dimethylsilyl derivatives and subjected to gas chromatography/mass spectrometry. When the macrophages were supplied with [U‐13C6]glucose prior to infection, but not during infection, label was detected only in Ala, Asp and Glu of the macrophage and bacterial protein with equal isotope distribution. When [U‐13C6]glucose was provided during the infection period, 13C label was found again in Ala, Asp and Glu from host and bacterial protein, but also in Ser, Gly, Thr and Val from the bacterial fraction. Mutants of L. monocytogenes defective in the uptake and catabolism of the C3‐metabolites, glycerol and/or dihydroxyacetone, showed reduced incorporation of [U‐13C6]glucose into bacterial amino acids under the same experimental settings. The 13C pattern suggests that (i) significant fractions (50–100%) of bacterial amino acids were provided by the host cell, (ii) a C3‐metabolite can serve as carbon source for L. monocytogenes under intracellular conditions and (iii) bacterial biosynthesis of Asp, Thr and Glu proceeds via oxaloacetate by carboxylation of pyruvate.
System‐level mapping of Escherichia coli response regulator dimerization with FRET hybrids
Authors: Gao Rong , Tao Yuan , Stock Ann M.
Published: July 2008

Two‐component signal transduction, featuring highly conserved histidine kinases (HKs) and response regulators (RRs), is one of the most prevalent signalling schemes in prokaryotes. RRs function as phosphorylation‐activated switches to mediate diverse output responses, mostly via transcription regulation. As bacterial genomes typically encode multiple two‐component proteins for distinct signalling pathways, the sequence and structural similarities of RR receiver domains create significant challenges to maintain interaction specificity. It is especially demanding for members of the OmpR/PhoB subfamily, the largest RR subfamily, which share a conserved dimerization interface for phosphorylation‐mediated transcription regulation. We developed a strategy to investigate RR interaction by analysing Förster resonance energy transfer (FRET) between cyan fluorescent protein (CFP)‐ and yellow fluorescent protein (YFP)‐fused RRs in vitro. Using the Escherichia coli RR PhoB as a model system, we were able to observe phosphorylation‐dependent FRET between fluorescent protein (FP)–PhoB proteins and validated the FRET method by determining dimerization affinity and dimerization‐coupled phosphorylation kinetics that recapitulated values determined by alternative methods. Further application of the FRET method to all E. coli OmpR/PhoB subfamily RRs revealed that phosphorylation–activated RR interaction is indeed a common theme for OmpR/PhoB subfamily RRs and these RRs display significant interaction specificity. Weak hetero‐pair interactions were also identified between several different RRs, suggesting potential cross‐regulation between distinct pathways.
Characterization of the NapGH quinol dehydrogenase complex involved in Wolinella succinogenes nitrate respiration
Authors: Kern Melanie , Simon Jörg
Published: July 2008

Nitrate respiration catalysed by the ε‐proteobacterium Wolinella succinogenes relies on the NapAGHBFLD system that comprises periplasmic nitrate reductase (NapA) and various other Nap proteins required for electron transport from menaquinol to NapA or maturation of Nap components. The W. succinogenes Nap system is unusual as electron transfer to NapA was shown previously to depend on both subunits of the predicted menaquinol dehydrogenase complex NapGH but did not require a cytochrome c of the NapC/NrfH family. Nonetheless, minor residual growth by nitrate respiration was observed in napG and napH gene inactivation mutants. Here, the question is addressed whether alternative membrane‐bound menaquinol dehydrogenases, like NrfH and NosGH, involved in nitrite or N2O reduction systems, are able to functionally replace NapGH. The phenotypes of various gene deletion mutants as well as strains expressing chimeric nap/nos operons demonstrate that NosH is able to donate electrons to the respiratory chain of nitrate respiration at a physiologically relevant rate, whereas NrfH and NosG are not. The iron‐sulphur protein NapG was shown to form a complex with NapH in the membrane but was detected in the periplasmic cell fraction in the absence of NapH. Likewise, NosH is able to bind NapG. Each of the eight poly‐cysteine motifs present in either NapG or NapH was shown to be essential for nitrate respiration. The NapG homologue NosG could not substitute for NapG, even after adjusting the cysteine spacing to that of NapG, implying that NapG and NosG are specific adapter proteins that channel electrons into either the Nap or Nos system. The current model on the structure and function of the NapGH menaquinol dehydrogenase complex is presented and the composition of the electron transport chains that deliver electrons to periplasmic reductases for either nitrate, nitrite or N2O is discussed.
Lack of TAR‐DNA binding protein‐43 (TDP‐43) pathology in human prion diseases
Authors: Isaacs A. M. , Powell C. , Webb T. E. , Linehan J. M. , Collinge J. , Brandner S.
Published: July 2008

Aims: TAR‐DNA binding protein‐43 (TDP‐43) is the major ubiquitinated protein in the aggregates in frontotemporal dementia with ubiquitin‐positive, tau‐negative inclusions and motor neurone disease. Abnormal TDP‐43 immunoreactivity has also been described in Alzheimer's disease, Lewy body diseases and Guam parkinsonism–dementia complex. We therefore aimed to determine whether there is TDP‐43 pathology in human prion diseases, which are characterised by variable deposition of prion protein (PrP) aggregates in the brain as amyloid plaques or more diffuse deposits. Material and methods: TDP‐43, ubiquitin and PrP were analysed by immunohistochemistry and double‐labelling immunofluorescence, in sporadic, acquired and inherited forms of human prion disease. Results: Most PrP plaques contained ubiquitin, while synaptic PrP deposits were not associated with ubiquitin. No abnormal TDP‐43 inclusions were identified in any type of prion disease case, and TDP‐43 did not co‐localize with ubiquitin‐positive PrP plaques or with diffuse PrP aggregates. Conclusions: These data do not support a role for TDP‐43 in prion disease pathogenesis and argue that TDP‐43 inclusions define a distinct group of neurodegenerative disorders.
Epidermal growth factor receptor extracellular domain mutations in primary glioblastoma
Authors: Idbaih A. , Aimard J. , Boisselier B. , Marie Y. , Paris S. , Crinière E. , Carvalho Silva R. , Laigle‐Donadey F. , Rousseau A. , Mokhtari K. , Thillet J. , Sanson M. , Hoang‐Xuan K. , Delattre J.‐Y.
Published: July 2008

Aims: Novel missense mutations of the epidermal growth factor receptor (EGFR) extracellular domain have been recently described in a large series of glioblastomas. Methods: The exons 2, 3, 7, 8 and 15 coding for the EGFR extracellular domain were sequenced in a series of 161 consecutive primary glioblastomas and correlated with clinical features of patients in order to determine whether these alterations are linked to specific clinical characteristics of the disease. Results: Missense mutations were observed in 18 cases (11.2%), and 4 novel mutations were detected, including G178C, A271C, C818A and C1860G. Mutations of the EGFR extracellular domain were not associated with overall survival or with age at onset of the disease. In contrast, the EGFR extracellular domain mutations were significantly associated with patients' gender. Indeed, 15 mutations were observed in men vs. 3 in women (P < 0.05). EGFR extracellular domain mutations were also strongly associated with EGFR amplification (P < 0.0001). Conclusions: To our knowledge, EGFR extracellular domain mutations are the first genomic abnormalities associated with gender in primary glioblastomas, although a link between mutations of the EGFR tyrosine kinase domain and gender has been previously made in lung cancer.
Effect of Specific Colostral Antibodies and Selected Lactobacilli on the Adhesion of Helicobacter pylori on AGS Cells and the Helicobacter‐Induced IL‐8 Production
Authors: Rokka S. , Myllykangas S. , Joutsjoki V.
Published: July 2008

Helicobacter pylori infection is the most common cause of gastritis, gastric ulcer and adenocarcinoma. It has proven difficult to cure because of its capability to develop strains resistant to antibiotics. The effect of three strains of lactic acid bacteria (LAB) and bovine colostral preparations on the adhesion of H. pylori NCTC 11637 on gastric adenocarcinoma (AGS) cells and on the interleukin (IL)‐8 production was studied. Before infection, H. pylori were pretreated with Lactobacillus plantarum MLBPL1, Lactobacillus rhamnosus GG, Lactococcus lactis, or with a colostral preparation with or without specific H. pylori antibodies. The relative number of H. pylori adhered on AGS cells was determined by urease test. IL‐8 produced by the cells was studied by enzyme‐linked immunosorbent assay. Colostral preparations with and without specific antibodies reduced the adhesion of H. pylori on AGS cells in a dose‐dependent manner. Live LAB at a concentration of 1010 CFU/ml reduced the adhesion by approximately 50% (P < 0.05). After the infection of AGS cells by H. pylori, the IL‐8 level rose up to about 10‐fold (5500 ± 1600 pg/ml). Pretreatment of H. pylori with colostral preparations or high concentrations of LAB prevented this IL‐8 rise. Similar effect was seen with live and heat‐killed LAB, the live LAB being more effective. Heat‐killed LAB at a concentration of 1010 CFU/ml rose the IL‐8 level of non‐infected cells significantly. Suppression of IL‐8 production by LAB or colostral products could have a suppressive effect on inflammation in Helicobacter infection.
Shallow lacustrine carbonate microfacies document orbitally paced lake‐level history in the Miocene Teruel Basin (North‐East Spain)
Authors: ABELS HEMMO A. , ABDUL AZIZ HAYFAA , CALVO JOSÉ P. , TUENTER ERIK
Published: July 2008

Results are presented of a detailed carbonate petrographic study of an Upper Miocene lacustrine mixed carbonate–siliciclastic succession in the Teruel Basin (Spain) with the aim of constraining lake‐level variability at different stratigraphic scales. Regular alternations of red to green mudstone and lacustrine limestone, termed the ‘basic cycle’, reflect lake‐level variations at the metre‐scale. In an earlier study, the basic cycle was shown to be controlled by the climatic precession cycle. Petrographic analysis made it possible to distinguish two main carbonate microfacies groups characteristic of very shallow transient and shallow permanent lake environments, respectively. In addition to the basic cyclicity, the microfacies analysis reveals lake‐level variations on a larger scale. As a consequence, the astronomical forcing hypothesis of the cyclicity in the Cascante section is explored further. A climate modelling study of orbital extremes indicates that high lake levels could relate to enhanced net winter precipitation and runoff during precession minima, consistent with Mediterranean geological data. Using this phase relationship, an astronomical tuning of the cycles is established starting from astronomical ages of magnetic reversal boundaries. Subsequently, successive basic cycles are correlated to precession minima. The tuning reveals an identical number of basic cycles in the Cascante section as precession‐related sapropel cycles in the deep marine succession at Monte dei Corvi (Italy), corroborating the precessional control of the basic cycles at Cascante. Lake‐level highstands in the large‐scale cycle identified by the microfacies analysis relate to maxima in both the ca 100 and 405 kyr eccentricity cycles, again consistent with Mediterranean geological data. Subtraction of the identified astronomically related (lake‐level) variations from the palaeoenvironmental record at Cascante indicates a shift to deeper and more permanent lacustrine environments in the upper half of the section. The cause of this shift remains unclear, but it may be linked to tectonics, non‐astronomical climate, long‐period astronomical cycles or autogenic processes.
Thermochemical sulphate reduction in the Upper Devonian Cairn Formation of the Fairholme carbonate complex (South‐West Alberta, Canadian Rockies): evidence from fluid inclusions and isotopic data
Authors: VANDEGINSTE VEERLE , SWENNEN RUDY , GLEESON SARAH A. , ELLAM ROB M. , OSADETZ KIRK , ROURE FRANÇOIS
Published: July 2008

The Fairholme carbonate complex is part of the extensively dolomitized Upper Devonian carbonate reefs in west‐central Alberta. The studied formations contain moulds (up to 10 cm in diameter), which are filled partially with (saddle) dolomite, quartz and calcite cements. These cements precipitated from a mixture of brines that acquired high salinity by dissolution of halite and brines derived from evaporated sea water. The fluids were warm (homogenization temperature of primary fluid inclusions of 76 to 200 °C) and saline (20 to 25 wt% NaCl equivalent) and testify to thermochemical sulphate reduction processes. The latter is deduced from S in solid inclusions, CO2 and H2S in volatile‐rich aqueous inclusions and depleted δ13C values down to −26‰ Vienna Pee Dee Belemnite. High 87Sr/86Sr values (0·7094 to 0·7110) of the cements also indicate interaction of the fluids with siliciclastic sequences. The thermochemical sulphate reduction‐related cements probably formed during early Laramide burial. Another (younger) calcite phase, characterized by depleted δ18O values (−23·9‰ to −13·9‰ Vienna Pee Dee Belemnite), low Na (27 to 37 p.p.m.) and Sr (39 to 150 p.p.m.) concentrations and non‐saline (∼0 wt% NaCl equivalent) fluid inclusions, is attributed to post‐Laramide meteoric water.
The effect of otic vehicle and concentration of dexamethasone on liver enzyme activities and adrenal function in small breed healthy dogs
Authors: Aniya Jennifer S. , Griffin Craig E.
Published: July 2008

Dexamethasone 0.1% in propylene glycol vehicle has been shown to cause adrenal suppression and increased liver enzyme concentrations in normal dogs. The objectives of this study were to determine if these effects are concentration or vehicle dependent and to evaluate a dexamethasone 0.01% solution. Twenty‐one privately owned normal dogs were included in this double‐blinded study. Chemistry panels and adrenocorticotropin hormone (ACTH) stimulation tests were performed on day 0 and 15. Dogs were randomly assigned treatment with dexamethasone 0.01% in saline, 0.1% in saline, or 0.1% in a commercial preparation (Tresaderm®: Merial, Duluth, GA, USA) in each ear twice daily for 2 weeks. Nineteen dogs completed the study. After 2 weeks of treatment, all dogs receiving dexamethasone 0.01% in saline had normal ACTH stimulation tests and liver enzyme values. In contrast, four of seven dogs (57.14%) receiving dexamethasone 0.1% in saline experienced adrenal suppression, and four of six dogs (66.67%) receiving Tresaderm® experienced adrenal suppression with three of those dogs (50%) experiencing marked adrenal suppression. No dogs receiving dexamethasone 0.1% in saline had increased liver enzyme concentration, while one of six dogs (16.67%) experienced a slight elevation in alkaline phosphatase. In conclusion, it appears that adrenal suppression caused by otic dexamethasone is concentration and perhaps vehicle dependent. Veterinarians who formulate dexamethasone 0.1% otic solutions should be cognizant of potential adrenal suppression similar to that seen with Tresaderm® although not to the same degree. Dexamethasone at 0.01% did not cause adrenal suppression or liver enzyme alterations after 2 weeks of treatment.
Mouse allergen exposure, wheeze and atopy in the first seven years of life
Authors: Phipatanakul W. , Celedón J. C. , Hoffman E. B. , Abdulkerim H. , Ryan L. M. , Gold D. R.
Published: July 2008

Background:  Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood.

Objective:  To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life.

Methods:  Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months.

Results:  Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis.

Conclusions:  Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.
Memory T cells in cancer immunotherapy: which CD8+ T‐cell population provides the best protection against tumours?
Authors: Perret R. , Ronchese F
Published: July 2008

Cancer immunotherapy strategies often fail because of immunosuppressive mechanisms present in the tumour‐bearing host. Adoptive T‐cell transfer therapy circumvents this problem by activating tumour‐specific CD8+ T cells in vitro and transferring them back into the patient. Classically, effector T cells have been used in these studies because of their potent anti‐tumour activity. However, it is becoming apparent that highly activated effector cells may become terminally differentiated, display impaired proliferation and survival in vivo, and mediate short‐term anti‐tumour effects. In contrast to effector cells, memory cells have enhanced proliferative potential and survival, and the potential to provide more robust and enduring protection against tumours. Here, we discuss key studies in the field of adoptive T‐cell transfer, along with some of our own results relating to this area. Based on the body of existing research, it is clear that CD8+ T cells with memory potential are superior to terminally differentiated effectors in mediating successful tumour clearance. Opinions remain divided as to whether the central memory or effector memory T‐cell subset is capable of providing the best protection against tumours. We propose that as these cell types have different but complementary benefits for the anti‐tumour immune response, the ideal cell population to use for adoptive T‐cell transfer should consist of a heterogeneous mixture of memory cells.
Investigation of CD69 as a new candidate gene for rheumatoid arthritis
Authors: Rueda B. , Fernandez‐Gutierrez B. , Balsa A. , Pacual‐Salcedo D. , Lamas J. R. , Raya E. , Gonzalez‐Gay M. A. , Martin J.
Published: July 2008

The aim of this study was to investigate the CD69 gene as a new functional candidate gene for rheumatoid arthritis (RA) genetic predisposition. A case–control association study including 933 RA patients and 800 healthy individuals was conducted. Five haplotype‐tagging single nucleotide polymorphisms (SNPs) (rs929615, rs3176806, rs4763299, rs11052877, and rs3176789) covering the CD69 gene coding, 5′ and 3′ untranslated regions were selected as CD69 genetic markers and genotyped using a Taqman 5′ allelic discrimination assay. No statistically significant differences were observed in the single marker association study with regard to either genotypic or allelic frequencies when considering the rs929615, rs3176806, rs4763299, rs11052877, and rs3176789 CD69 SNPs independently. According to these findings, no statistically significant skewing was observed between the RA patients and the controls in the distribution of CD69 haplotypes. In summary, our results do not support a major role for the CD69 gene polymorphisms in RA genetic predisposition in our population.
Preservation of organs from brain dead donors with hyperbaric oxygen
Authors: Bayrakci Benan
Published: July 2008

Abstract:  Hyperbaric oxygen therapy is a technology that involves oxygen treatment at supra‐atmospheric pressures in high concentrations, generating increased levels of physically dissolved oxygen in blood plasma. This form of transported oxygen, compared with oxygen chemically bound to hemoglobin, is able to enter tissues with minimal or almost no blood flow. Experimental studies have suggested that hyperoxemia provided by hyperbaric oxygen may be beneficial in the treatment of reperfusion injury. Organs procured from brain‐dead hyperbaric oxygen‐treated donors may have less cellular injury from ischemia, reperfusion, and no‐reflow phenomenon, thus yielding organs in an optimized state for transplantation. This current report consists of a gratifying experience about hyperbaric oxygen treatment playing a possible role on preservation of donor organs in vivo. In the siblings reported here, improved organ function prior to transplantation and the successful organ functioning after transplantation suggests the possible beneficial effect of hyperbaric oxygen treatment on the ischemic insult generated from brain death and repetitive cardiac arrests. Hyperbaric oxygen seems to be a promising candidate as a bridge to transplantation, keeping the donated organs viable until the harvesting procedure can take place for potential brain dead donors. This experience may lead to further investigations on hyperbaric oxygen’s role in donor organ preservation.
Influence of cytokine and intercellular adhesion molecule‐1 gene polymorphisms on acute rejection in pediatric renal transplantation
Authors: Mendoza‐Carrera Francisco , Ojeda‐Durán Simón , Angulo Eduardo , Rivas Fernando , Macías‐López Griselda , Buen Eliseo Portilla‐de , Leal Caridad
Published: July 2008

Abstract:  Immune response regulation by cytokines is a key to understanding AGR. The influence of the functional polymorphisms in genes coding for TNF‐α (−308G > A), IL‐10 (−819C > T, and −1082A > G), IFN‐γ [(CA)n], TGF‐β1 (+869T > C), and iCAM‐1 (R241G and E469K), in addition to HLA and gender matching on the presentation of AGR in 51 pediatric renal recipients during a 36‐month post‐transplantation follow‐up were analyzed. Also, donors and a control group were genotyped. All groups were within Hardy‐Weinberg equilibrium for all polymorphisms except IL‐10–819C > T and TNF‐α (p < 0.005 and p < 0.01, respectively) in recipients. Transplants with gender mismatch showed a higher risk for AGR than those between individuals with gender match (OR, 4.227; p = 0.010). Recipients with a high‐production compared with low‐production TNF‐α allele experienced earlier AGR (p = 0.030), and those with high‐production alleles of both TNF‐α and IFN‐γ showed a further increased risk (OR = 11.129, p = 0.024). These findings support the notion that a single genotype cannot by itself explain an event as complex as AGR. The sum or combination of different specific alleles of these genes could better account for the immune response to an allograft.
Relative longevity and field metabolic rate in birds
Authors: MØLLER A. P.
Published: July 2008

Metabolism is a defining feature of all living organisms, with the metabolic process resulting in the production of free radicals that can cause permanent damage to DNA and other molecules. Surprisingly, birds, bats and other organisms with high metabolic rates have some of the slowest rates of senescence begging the question whether species with high metabolic rates also have evolved mechanisms to cope with damage induced by metabolism. To test whether species with the highest metabolic rates also lived the longest I determined the relationship between relative longevity (maximum lifespan), after adjusting for annual adult survival rate, body mass and sampling effort, and mass‐specific field metabolic rate (FMR) in 35 species of birds. There was a strongly positive relationship between relative longevity and FMR, consistent with the hypothesis. This conclusion was robust to statistical control for effects of potentially confounding variables such as age at first reproduction, latitude and migration distance, and similarity in phenotype among species because of common phylogenetic descent. Therefore, species of birds with high metabolic rates senesce more slowly than species with low metabolic rates.