bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner
Authors: Tsao Chang-Huei , Su Hong-Lin , Lin Yi-Ling , Yu Han-Pang , Kuo Shu-Ming , Shen Ching-I , Chen Ching-Wen , Liao Ching-Len
Published: July 2008

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, replicates primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected cells. This study investigated the hierarchical activation of the caspase network induced by JEV infection. It was found that JEV activated the initiators caspase-8 and -9, as well as effector caspase-3, in infected baby hamster kidney and mouse neuroblastoma (N18) cells. In neuronal N18 cells, JEV infection triggered cytochrome c release from mitochondria, which in turn activated caspase-9 and -3. Treatment of JEV-infected N18 cells with cyclosporin A or ruthenium red, which attenuate mitochondrial injuries, blocked activation of caspase-9 or -3, typifying that, in neuronal cells, this apoptosis involves the mitochondrial pathway. Alternatively, in caspase-3-deficient MCF-7 cells, JEV persisted and readily triggered a typical apoptotic response, including cytochrome c release and full activation of caspase-9 and -8 along with caspase-6, indicating that JEV did not require caspase-3 to manifest caspase-8 activation and apoptosis. Interestingly, a Fas-associated death-domain-containing protein (FADD) dominant-negative mutant, which interfered with transmission of the extracellular death signals into cells through the Fas/tumour necrosis factor (TNF) receptor, failed to block JEV-induced apoptosis and caspase-8 activation, implying that receptor oligomerization of the Fas/TNF pathway might not participate in JEV-induced apoptosis. Taken together, these results illustrate that JEV infection triggers caspase cascades involving the initiators caspase-8 and -9, probably through FADD-independent but mitochondrion-dependent pathways.
Conserved archetypal configuration of the transcriptional control region during the course of BK polyomavirus evolution
Authors: Yogo Yoshiaki , Zhong Shan , Xu Yawei , Zhu Mengyun , Chao Yuegen , Sugimoto Chie , Ikegaya Hiroshi , Shibuya Ayako , Kitamura Tadaichi
Published: July 2008

BK polyomavirus (BKV) is widespread among humans, asymptomatically infecting children and then persisting in renal tissue. The transcriptional control region (TCR) of the BKV genome is variable among clinical isolates. Thus, archetypal TCRs with a common basic configuration generally occur in BKV isolates from the urine of immunocompromised patients, but rearranged TCRs that possibly arise from the archetypal configuration have also been detected in clinical specimens. To examine the hypothesis that archetypal strains represent wild-type strains circulating in the human population (the archetype hypothesis), we analysed 145 complete viral genomes amplified directly from the urine of non-immunocompromised individuals worldwide. These genomes included 82, three, two and 58 sequences classified as belonging to subtypes I, II, III and IV, respectively. Rearranged TCRs with long duplications or deletions were detected from two subtype I and two subtype IV genomes, but not from the other 141 genomes (thus, the TCRs of these genomes were judged to be archetypal). The variations in the archetypal TCRs were nucleotide substitutions and single-nucleotide deletions, most of which were unique to particular subtypes or subgroups. We confirmed that the four complete BKV genomes with rearranged TCRs did not form a unique lineage on a phylogenetic tree. Collectively, the findings demonstrate that the archetypal TCR configuration has been conserved during the evolution of BKV, providing support for the archetype hypothesis. Additionally, we suggest that ‘archetype’ should be used as a conceptual term that denotes a prototypical structure that can generate various rearranged TCRs during viral growth in vivo and in vitro.
Distinctive pattern of sequence polymorphism in the NS3 protein of hepatitis C virus type 1b reflects conflicting evolutionary pressures
Authors: Irausquin Stephanie Jiménez , Hughes Austin L.
Published: July 2008

Analysis of complete polyprotein-encoding sequences of hepatitis C virus genotype 1b (HCV-1b) showed evidence not only of past purifying selection but also of abundant slightly deleterious non-synonymous variants subject to ongoing purifying selection. The NS3 protein (with protease and NTPase/helicase activity) revealed less evidence of purifying selection acting on the cytotoxic T cells (CTL) epitopes than did the other proteins, whereas outside the CTL epitopes NS3 was more conserved than the other proteins. Moreover, NS3 showed a high incidence of forward-and-backward or parallel non-synonymous changes in CTL epitopes, as measured by the consistency index across the phylogeny of HCV-1b genomes computed at non-singleton non-synonymous polymorphic sites. This result implies that certain non-synonymous mutations have recurred frequently throughout the phylogeny in the codons encoding the epitopes in NS3. This pattern is most easily explained by the frequent re-occurrence of the same set of escape mutations in CTL epitopes of NS3, which are selectively favoured within hosts expressing the presenting class I major histocompatibility complex molecule, but are subject to purifying selection at the population level. The fact that this pattern is most strikingly observed in the case of NS3 suggests that the evolutionary conflict between immune escape and functional constraint on the protein is more acute in the case of NS3 than any of the other proteins of HCV-1b.
Bluetongue virus: dissection of the polymerase complex
Authors: Roy Polly
Published: July 2008

Bluetongue is a vector-borne viral disease of ruminants that is endemic in tropical and subtropical countries. Since 1998 the virus has also appeared in Europe. Partly due to the seriousness of the disease, bluetongue virus (BTV), a member of genusOrbiviruswithin the familyReoviridae, has been a subject of intense molecular study for the last three decades and is now one of the best understood viruses at the molecular and structural levels. BTV is a complex non-enveloped virus with seven structural proteins arranged in two capsids and a genome of ten double-stranded (ds) RNA segments. Shortly after cell entry, the outer capsid is lost to release an inner capsid (the core) which synthesizes capped mRNAs from each genomic segment, extruding them into the cytoplasm. This requires the efficient co-ordination of a number of enzymes, including helicase, polymerase and RNA capping activities. This review will focus on our current understanding of these catalytic proteins as derived from the use of recombinant proteins, combined with functional assays and thein vitroreconstitution of the transcription/replication complex. In some cases, 3D structures have complemented this analysis to reveal the fine structural detail of these proteins. The combined activities of the core enzymes produce infectious transcripts necessary and sufficient to initiate BTV infection. Such infectious transcripts can now be synthesized whollyin vitroand, when introduced into cells by transfection, lead to the recovery of infectious virus. Future studies thus hold the possibility of analysing the consequence of mutation in a replicating virus system.
An enterovirus strain isolated from diabetic child belongs to a genetic subcluster of echovirus 11, but is also neutralised with monotypic antisera to coxsackievirus A9
Authors: Al-Hello Haider , Paananen Anja , Eskelinen Mervi , Ylipaasto Petri , Hovi Tapani , Salmela K. , Lukashev Alexander N. , Bobegamage Shubhada , Roivainen Merja
Published: July 2008

An enterovirus strain (designated D207) isolated from a Slovakian diabetic child and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid cytolysis coinciding with severe functional damage of the surviving cells in primary cultures of human pancreatic islets. This finding prompted us to clone the isolate for full-length genome sequencing and molecular characterization as the prototype strain of CAV-9 is known to cause only minimal damage to insulin-producing β-cells. Based on capsid-coding sequence comparisons, the isolate turned out to be echovirus 11 (E-11). Phylogenetic analyses demonstrated that E-11/D207 was closely related to a specific subgroup B of E-11 strains known to cause uveitis. To study further antigenic properties of isolate E-11/D207 and uveitis-causing E-11 strains, neutralization experiments were carried out with CAV-9- and E-11-specific antisera. Unlike the prototype strains, the isolate E-11/D207 and uveitis-causing E-11 strains were well neutralized with both CAV-9- and E-11-specific antisera. Attempts to identify recombination of the capsid coding sequences as a reason for double-reactivity using the Simplot analysis failed to reveal major transferred motifs. However, peptide scanning technique was able to identify antigenic regions of capsid proteins of E-11/D207 as well as regions cross-reacting with an antiserum raised to CAV-9. Thus, double specificity of E-11/D207 seems to be a real characteristic shared by the phylogenetically closely related virus strains in the genetic subgroup B of E-11.
Initiation of hepatitis B virus genome replication and production of infectious virus following delivery in HepG2 cells by novel recombinant baculovirus vector
Authors: Lucifora J. , Durantel D. , Belloni L. , Barraud L. , Villet S. , Vincent I. E. , Margeridon-Thermet S. , Hantz O. , Kay A. , Levrero M. , Zoulim F.
Published: July 2008

One of the major problems in gaining further insight into hepatitis B virus (HBV)/host-cell interactions is to improve the existing cellular models for the study of HBV replication. The first objective of this study was to improve the system based on transduction of HepG2 cells with a recombinant baculovirus to study HBV replication. A new HBV recombinant baculovirus, Bac-HBV-1.1, in which the synthesis of pre-genomic RNA is driven by a strong mammalian promoter, was generated. Transduction with this new recombinant baculovirus led to higher levels of HBV replication in HepG2 cells compared with levels obtained with previously described baculovirus vectors. The initiation of a complete HBV DNA replication cycle in Bac-HBV-1.1-transduced HepG2 cells was shown by the presence of HBV replicative intermediates, including covalently closed circular DNA (cccDNA). Only low levels of cccDNA were detected in the nucleus of infected cells. Data showed that cccDNA resulted from the recycling of newly synthesized nucleocapsids and was bound to acetylated histones in a chromatin-like structure. HBV particles released into the supernatant of transduced HepG2 cells were infectious in differentiated HepaRG cells. Several Bac-HBV-1.1 baculoviruses containing HBV strains carrying mutations conferring resistance to lamivudine and/or adefovir were constructed. Phenotypic analysis of these mutants confirmed the results obtained with the transfection procedures. In conclusion, an improved cell-culture system was established for the transduction of replication-competent HBV genomes. This will be useful for future studies of the fitness of HBV mutants.
Differential reactivity of putative genotype 2 hepatitis C virus F protein between chronic and recovered infections
Authors: Chuang Wing Chia-Ming , Allain Jean-Pierre
Published: July 2008

To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression in vitro/in vivo of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture. An ELISA was developed and applied to samples from patients with chronic infection or recovered infection of various genotypes. The anti-F-2 response in 117 samples showed a significantly higher reactivity in chronic than in recovered HCV-infected blood donors (P<0.001), but no difference was found among genotypes. However, the correlation between anti-F and anti-core was more significant in genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly higher in chronic than in recovered individuals (P<0.0001). Antibody titres to recombinant genotype 2 core protein or to genotype 1 multiple proteins used in commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This study thus demonstrated the antigenicity of genotype 2 HCV F protein, although the exact location of the natural frameshift position remains unknown. The difference in anti-F-2 response between chronic and recovered infection, the cross-reactivity irrespective of genotype and the correlation of antibody response with structural and non-structural antigens suggest that the immune response to F protein is an integral part of the natural HCV infection.
Detection of four genetic subgroup-specific antibodies to human metapneumovirus attachment (G) protein in human serum
Authors: Endo Rika , Ebihara Takashi , Ishiguro Nobuhisa , Teramoto Shinobu , Ariga Tadashi , Sakata Chikako , Hayashi Akio , Ishiko Hiroaki , Kikuta Hideaki
Published: July 2008

Human metapneumovirus (hMPV) strains are classified into two genetic groups, A and B, each of which is further divided in two genetic subgroups, A1, A2, B1 and B2. hMPV encodes two major surface glycoproteins, the fusion (F) and attachment (G) proteins, which may be immunogenic and protective antigens. Although the amino acid sequences of hMPV F protein are highly conserved, those of the G protein are highly variable with low amino acid identity between the two groups. To address the antigenic variation between the genetic subgroups, we developed an immunofluorescence assay (IFA) method using Trichoplusia ni (Tn5) insect cells infected with each recombinant baculovirus-expressed hMPV G (Bac-G) protein of the four genetic subgroups. The titre of each antibody to the four Bac-G proteins was measured by the IFA in 12 paired serum samples obtained from children infected with hMPV of each genetic subgroup. Although 11 of the 12 acute-phase serum samples in paired samples were negative for the antibody to any Bac-G proteins, all of the convalescent-phase serum samples in those paired samples were positive for the antibody to only one of the four Bac-G proteins of the infecting genotype of hMPV. Since the antibody response to hMPV G protein was transient and genetic subgroup-specific without cross-reactivity, four genetic subgroups on the basis of hMPV G protein could be identified as different serotypes. This assay may be useful for the study of immune responses of humans to different hMPV strains, especially for clarifying the risk of reinfection with hMPV.
Macrophyte species diversity in formerly cultivated wetlands in Uganda
Authors: Esaete Josephine , Kasenene John M. , Totland Ørjan , Obua Joseph
Published: July 2008

The diversity of major macrophytes was assessed in cultivated areas in Bukasa and Kinawataka wetlands in Central Uganda. One thousand and seventy‐two plots of 1 × 1 m were established in 69 cultivated areas. Data were collected on species richness and abundance. Two‐way analysis of covariance (ANCOVA) showed how cropping regimes affected macrophyte species richness and abundance. There were 127 plant species belonging to 37 families in cultivated areas. Of the 127 species, 42 were macrophytes and of the 37 families, fourteen contained macrophyte species. Plant species diversity was higher in the short‐term cropping regime areas (11.3 species per 1 m2) than in the long‐term cropping regime areas (9.3 species per 1 m2). However, macrophyte species richness was similar in the short‐term (3.2 species per 1 m2) and the long‐term (3.3 species per 1 m2) cropping regimes. The dominant families were Poaceae, Asteraceae and Cyperaceae with more than ten species each. The higher plant species diversity in cultivated areas than in uncultivated was because of nonmacrophyte species, thus cropping regime does not influence macrophyte species diversity. Increase in diversity of nonmacrophyte species in short‐term cropping regime implies that the use of wetlands for agricultural crop growing may alter plant species composition and diversity during secondary succession.
A peri‐operative statin update for non‐cardiac surgery. Part I: The effects of statin therapy on atherosclerotic disease and lessons learnt from statin therapy in medical (non‐surgical) patients
Authors: Biccard B. M.
Published: July 2008

The utility of peri‐operative statin therapy is currently considered to be inconclusive. To provide a platform for more meaningful peri‐operative statin literature in the future, this is the first of two review articles evaluating peri‐operative statin therapy. This review examines the predictors of cardiovascular outcome and therapeutic targets which are established in medical (non‐surgical) patients. In patients with stable coronary artery disease at least 4–6 weeks of standard statin therapy are required to realise most of the beneficial cellular and metabolic effects of statin therapy. Low‐density lipoprotein‐cholesterol reduction is associated with improved survival in these patients. In comparison, patients who sustain an acute coronary event require high‐dose statin therapy probably initiated within 24 h with a therapeutic target of C‐reactive protein reduction. Withdrawal of statin therapy results in a rapid return to endothelial dysfunction and amplification of the inflammatory process, which may increase cardiovascular risk.
Peritonsillar infiltration with bupivacaine and pethidine for relief of post‐tonsillectomy pain: a randomised double‐blind study
Authors: Nikandish R. , Maghsoodi B. , Khademi S. , Motazedian S. , Kaboodkhani R.
Published: July 2008

Previous studies of infiltration of local anaesthetics in children undergoing tonsillectomy resulted in conflicting results. The aim of this study was to evaluate the effect of the peritonsillar injection of bupivacaine and pethidine on postoperative pain in children undergoing snare‐dissection tonsillectomy. In a double‐blind study, 80 children (aged 7–15 years) were randomly divided into two groups receiving peritonsillar injection of either bupivacaine (1 mg.kg−1) and pethidine (1 mg.kg−1) in adrenaline 1 : 200 000 (treatment group) or an equivalent volume of saline (placebo group) pre‐operatively. The time needed for first demand of analgesia and analgesic consumption to reduce the visual analogue scale (VAS) for resting throat pain to≤30, the VAS for pain on swallowing, drinking liquid and eating a soft diet, incidence of nausea and vomiting, and the need for rescue anti‐emetics in the first 24 h after operation were compared in both groups. The combination of bupivacaine and pethidine could significantly decrease the consumption of analgesics for resting pain at 4, 6, 8, 12, and 24 h after operation but did not reduce pain on swallowing, drinking liquid and eating a soft diet. The times to demand of first dose of analgesic and to first oral intake were not significantly different. The overall satisfaction of patients in relation to relief of postoperative pain was not significantly different between the two groups. Although peritonsillar injection of pethidine and bupivacaine in children reduces the analgesic consumption, it does not affect the dynamic pain state in the first 24 h after snare‐dissection tonsillectomy.
Osmotic demyelination syndrome following rapid correction of hyponatraemia
Authors: Snell D. M. , Bartley C.
Published: July 2008

We report a case of a young male with adrenal hypoplasia who presented following water intoxication with severe hyponatraemia and seizures. He required a period of intensive care and over the initial 24 h his serum sodium corrected at average of 0.9 mmol.l−1 h−1. He subsequently developed osmotic demyelination syndrome. Following supportive treatment he made a full recovery. Severe hyponatraemia carries a risk of cerebral oedema with a significant mortality, yet correcting it too rapidly can result in osmotic demyelination syndrome, again with potentially disastrous consequences. It may be difficult to determine the duration and aetiology of the hyponatraemia and this is necessary to guide treatment. There is no consensus about the optimal rate of correction of hyponatraemia but formulae such as the Adrogue and Madias formula can be used to guide treatment with normal or hypertonic saline. Continuous veno‐venous haemofiltration has been used effectively in this setting.
Magnetic polarity stratigraphy of the Neogene foreland basin deposits of Nepal
Authors: Ojha T. P. , Butler R. F. , DeCelles P. G. , Quade J.
Published: July 2008

The early Miocene Dumri Formation and middle Miocene–Pliocene Siwalik Group were deposited in the Himalayan foreland basin in response to uplift and erosion in the Himalayan fold‐thrust belt. We report magnetostratigraphic data from four sections of these rocks in Nepal. Three of these sections are in the Siwalik Group in the hanging wall of the Main Frontal thrust, and one section is from the Dumri Formation in the hanging wall of the Main Boundary thrust (MBT). Thermal demagnetization experiments demonstrate that laminated siltstones yield palaeomagnetic data useful for tectonic and magnetostratigraphic studies whereas other lithofacies yield data of questionable reliability. Magnetostratigraphic data have been acquired from 297 sites within a 4200‐m‐thick section of Siwalik deposits at Surai Khola. The observed sequence of polarity zones correlates with the geomagnetic polarity time scale (GPTS) from chron C5Ar.1n to chron C2r.2n, spanning the time frameca. 12.5–2.0 Ma. At Muksar Khola (eastern Nepal), 111 palaeomagnetic sites from a 2600‐m‐thick section of the Siwalik Group define a polarity zonation that correlates with the GPTS from chron C4Ar.2n to chron C2Br.1r, indicating an age range ofca. 10.0–3.5 Ma. At Tinau Khola, 121 sites from a 1824‐m‐thick section of the Siwalik Group are correlated to chrons C5An.1n through C4r.1n, equivalent to the time spanca. 11.8–8.1 Ma. At Swat Khola, 68 sites within a 1200‐m‐thick section of lower Miocene Dumri Formation are correlated with chrons C6n through C5Bn.2n, covering the time spanca. 19.9–15.1 Ma. Together with previous results from Khutia Khola and Bakiya Khola, these data provide the first magnetostratigraphic correlation along nearly the entire NW–SE length of Nepal. The correlation demonstrates that major lithostratigraphic boundaries in the Siwalik Group are highly diachronous, with roughly 2 Myr of variability. In turn, this suggests that the major sedimentological changes commonly inferred to reflect strengthening of the Asian monsoon are not isochronous. Sediment accumulation curves exhibit a 30–50% increase in accumulation rate in four of the five sections of the Siwalik Group, but the timing of this increase ranges systematically from ∼11.1 Ma in western Nepal to ∼5.3 Ma in eastern Nepal. If this increase in sediment accumulation rate is interpreted as a result of more rapid subsidence owing to thrust loading in the Himalaya, then the diachroneity of this increase suggests lateral propagation of a major thrust system, perhaps the MBT, at a rate ofca. 103 mm year−1across the length of Nepal.
Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort
Authors: Asarnoj A. , Östblom E. , Kull I. , Lilja G. , Pershagen G. , Hedlin G. , Van Hage M. , Wickman M.
Published: July 2008

Background
There is limited knowledge of the development of IgE‐antibody levels over time in childhood, with respect to persistency and co‐sensitization to specific inhalant allergens.

Methods
Data from 2033 children participating in the BAMSE birth cohort was used. Background factors and clinical parameters were obtained and IgE antibody (ab) levels to eight common airborne allergens were measured (0.35 kUA/L) when the children were 4 and 8 years of age.

Results
Between 4 and 8 years the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At 4 years IgE‐ab to birch and cat dominated, whereas at the age of 8, there was a considerable increase in the proportion of sensitization to timothy and dog. Except for mites and moulds, IgE‐ab levels to all aeroallergens increased significantly between 4 and 8 years among those already sensitized at 4. Transient sensitization to inhalant allergen was uncommon. Furthermore, sensitization to birch pollen at 4 years increased the risk for becoming sensitized to timothy, cat and dog later in life. Such an association was not observed among those sensitized primarily to animal dander.

Conclusions
There is a prominent process of sensitization at pre‐school age to inhalant allergens, and in Northern Europe sensitization to birch pollen early in life seems to be important for this process. Such a process has a probable impact on the development of allergic disease in the growing child.
Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma
Authors: Barbas A. S. , Downing T. E. , Balsara K. R. , Tan H. E. , Rubinstein G. J. , Holzknecht Z. E. , Collins B. H. , Parker W. , Davis R. D. , Lin S. S.
Published: July 2008

Background  Chronic aspiration associated with gastro oesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice.

Materials and methods  Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57.

Results  Chronic aspiration of 10 µL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin‐induced airway hypersensitivity was associated with a trend toward decreased production of antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response.

Conclusion  These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.
Parental diabetes in Taiwanese diabetic women with and without previous gestational diabetes
Authors: Tseng C. H.
Published: July 2008

Background   Gestational diabetes mellitus (GDM) is reported to be associated with maternal but not paternal diabetes. This study examined the relative contribution of maternal and paternal diabetes among type 2 diabetic women with and without a GDM history.

Materials and methods   A total of 48 502 type 2 diabetic women from a national sample were interviewed by telephone. Among them, 510 reported a GDM history. Parental diabetes was compared between patients with and without a GDM history considering the confounding effects of age, body mass index, smoking, hypertension, duration of diabetes and insulin use.

Results   Patients with a GDM history were younger in age, had younger age of onset, longer duration of diabetes, slightly lower body mass index, higher prevalence of insulin use and lower prevalence of hypertension, but smoking rates were similar. The percentages of parental diabetes of nil, mother only, father only and both father and mother for those without a GDM history were 76·2, 15·2, 5·8 and 2·8%, respectively; and were 47·8, 26·8, 17·5 and 7·9%, respectively, for those with a GDM history (P < 0·001). The adjusted odds ratios for patients with versus without a GDM history for parental diabetes of nil, mother only, father only, and both father and mother were 1·000, 1·210 (0·948–1·544), 1·783 (1·341–2·371) and 2·094 (1·440–3·045), respectively.

Conclusions   Although maternal diabetes is more commonly seen, the disproportionately higher paternal diabetes in patients with a GDM history suggests an important role for paternal diabetes on the development of GDM into type 2 diabetes mellitus.
Interannual and seasonal changes in the soil exchange rates of monoterpenes and other VOCs in a Mediterranean shrubland
Authors: Asensio D. , Peñuelas J. , Prieto P. , Estiarte M. , Filella I. , Llusià J.
Published: July 2008

Information about soil VOC inventories and exchange rates in different soils is very scarce. Seasonality of soil VOC exchange rates is also largely unknown, despite the increasing interest in some soil volatile compounds, such as monoterpenes, because of their important role in soil ecology. We aimed to explore and quantify soil VOC exchange rates in a Mediterranean shrubland and their seasonality. Measurements of soil VOC exchange were taken using GC‐MS and PTR‐MS techniques, together with soil temperature, soil moisture and soil CO2 efflux measurements, during two annual campaigns with contrasting precipitation. Methanol, acetic acid, ethyl acetate, acetaldehyde, acetone, C3 and C4 carbonyls (such as methyl ethyl ketone), α‐pinene and limonene, showed the highest emission rates. Maximum soil monoterpene emission rates were very low (0.003 nmol m−2 s−1) compared with foliar monoterpene emission rates. The emission rates of the other VOCs were also low (maximum 0.8 nmol m−2 s−1) except for methanol (1.2 nmol m−2 s−1). Maximum soil uptake rates for some VOCs, such as methanol and acetonitrile (ranging from −0.1 to −0.5 nmol m−2 s−1) were, however, comparable with foliar uptake rates. Further studies are needed to corroborate these results and the possible importance of the soil VOC sink in regional chemistry‐climate models. Long‐term severe drought increased soil monoterpene emission rates in this Mediterranean shrubland. The increases seem to be linked to changes in the soil’s physical properties induced by low soil moisture. Unlike monoterpenes, other soil VOC emission rates decreased when soil moisture was low. The results suggest a seasonal control of soil temperature on the emission rates of monoterpenes and other VOCs. The emission rates increase with soil temperature. Positive correlations between the VOC exchange rates and the soil CO2 fluxes suggest that phenology of roots and microorganisms also controls seasonal changes in soil VOCs in this Mediterranean shrubland.
Pathways for algal recolonization in seasonally‐flowing streams
Authors: ROBSON BELINDA J. , MATTHEWS TY G. , LIND PETER R. , THOMAS NIGEL A.
Published: July 2008

1. In semi‐arid climates, seasonally‐flowing streams provide most of the water required for human use, but knowledge of how water extraction affects ecological processes is limited. Predicted alterations in stream flows associated with the impacts of climate change further emphasize the need to understand these processes. Benthic algae are an important base for stream food webs, but we have little knowledge of how algae survive dry periods or respond to altered flow regimes.

2. We sampled 19 streams within the Grampians National Park, south‐eastern Australia and included four components: a survey of different drought refuges (e.g. permanent pools, dry biofilm on stones and dry leaf packs) and associated algal taxa; a survey of algal regrowth on stones after flows recommenced to determine which refuges contributed to regrowth; reciprocal transplant experiments to determine the relative importance of algal drift and regrowth from dry biofilm in recolonization; direct measurement of algal drift to determine taxonomic composition in relation to benthic assemblage composition.

3. Algae showed little specificity for drought refuges but did depend on them; no species were found that were not present in at least one of the perennial pool, dry biofilm or leaf pack refuges. Perennial pools were most closely correlated with the composition of algal assemblages once flows resumed, but the loss or gain of perennial pools that might arise from stream regulation is unlikely to affect the composition of algal regrowth. However, regulated streams were associated with strong increases in algal density in dry biofilm, including increased densities of Cyanobacteria.

4. A model for algal recolonization in seasonally‐flowing streams identified three pathways for algal recolonization (drift‐dependent, dry biofilm‐dependent and contributions from both), depending on whether streams are diatom‐dominated or dominated by filamentous algae. The model predicted the effects of changes to stream flow regimes on benthic algal recolonization and provides a basis for hypotheses testable in streams elsewhere.
Variation in the trophic basis of production and energy flow associated with emergence of larval salamander assemblages from forest ponds
Authors: REGESTER KURT J. , WHILES MATT R. , LIPS KAREN R.
Published: July 2008

1. Larval amphibians are a dominant consumer in many freshwater systems, yet limited data on energy transfers between aquatic food resources and larvae and between metamorphosed larvae and adjacent habitats preclude an accurate assessment of their roles as links between aquatic and terrestrial food webs.

2. During 2003–04, we derived prey‐specific assimilation efficiencies, analysed stomach contents, and intensively sampled ambystomatid salamander assemblages in four ponds to quantify the trophic basis of larval production. Using estimates of the contribution of each prey taxon to larval production, we constructed quantitative food webs and assessed variation in pathways of energy flow associated with emergences.

3. Overall, metamorphosed salamanders exported 3–8% of total prey production, required to account for total salamander production, to adjacent forest. Aquatic insects, zooplankton and amphibian prey were most important to energy flow associated with emergence; amounts of larval production attributed to each of these prey types shifted during development and varied among salamander taxa.

4. The majority of variation in the trophic basis of production among species was attributed to copepods (Cyclopidae) and three families of aquatic insects (Chironomidae, Chaoboridae and Culicidae). Dominant prey types contributing to the production of metamorphosed salamanders varied among ponds, representing different pathways for energy transfers between aquatic resources and forest habitats. These findings further our understanding of the ecological roles of amphibians and thus the consequences of amphibian declines and extinctions.
PAX‐5 is invariably expressed in B‐cell lymphomas without plasma cell differentiation
Authors: Dong H Y , Browne P , Liu Z , Gangi M
Published: July 2008

Aims:  The B‐cell‐specific transcription factor PAX‐5 is physiologically expressed in normal B cells and silenced in plasma cells. The aim of this study was to determine whether PAX‐5 expression is universal among B‐cell malignancies.

Methods and results:  A wide spectrum of B‐cell malignancies were subjected to immunohistochemical analysis for PAX‐5 expression. The study was especially focused on cases lacking CD20, such as precursor B‐cell acute lymphoblastic leukaemia (preB‐ALL), CD20− B‐cell lymphomas, classical Hodgkin’s lymphoma (CHL) and B‐cell lymphomas with significant plasmacytic differentiation. Strong PAX‐5 expression was identified, without exception, in all cases of CD20+ B‐lymphoproliferative disorders. It was also invariably detected in 31/31 cases of preB‐ALL, 14/14 cases of CD20− diffuse large B‐cell lymphoma without plasmacytic differentiation and 26/26 CD20− B‐cell lymphoma status post rituximab treatment. The vast majority of CHLs had unequivocal PAX‐5 expression of varying intensity (80/86). However, variants of B‐cell malignancies with characteristic plasmacytic differentiation exhibited no detectable PAX‐5 expression (0/17).

Conclusions:  PAX‐5 is the most sensitive and reliable immunohistochemical marker for B‐cell malignancies. Lack of PAX‐5 expression correlates with the presence of marked plasma cell differentiation.
Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases
Authors: Diebold J , Le Tourneau A , Marmey B , Prevot S , Müller‐Hermelink H K , Sevestre H , Molina T , Billotet C , Gaulard P , Knopf J‐F , Bendjaballah S , Mangnan‐Marai A , Brière J , Fabiani B , Audouin J
Published: July 2008

Aims:  To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp.

Methods and results:  Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10–150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases.

Conclusions:  SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.
Malignant lesions in the ventral prostate of alloxan‐induced diabetic rats
Authors: Ribeiro Daniele Lisboa , Marques Silvio Fernando Guideti , Alberti Sandra , Spadella César Tadeu , Manzato Antônio José , Taboga Sebastião Roberto , Dizeyi Nishtman , Abrahamsson Per‐Anders , Góes Rejane Maira
Published: July 2008

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra‐epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl‐2‐positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.
Effects of early postnatal hyperglycaemia on renal cortex maturity, endothelial nitric oxide synthase expression and nephron deficit in mice
Authors: Cunha Ana Rosa , Aguila Marcia Barbosa , Mandarim‐de‐Lacerda Carlos Alberto
Published: July 2008

The influence of hyperglycaemia on nephrogenesis on Swiss mice pups treated with streptozotocin (STZ) (40 mg/kg, i.p.) was studied after birth, at 7 and 21 days. Kidneys were prepared for light microscopy, immunohistochemistry and stereology. In 7‐day‐old pups, both immature and mature glomeruli were evaluated separately. Proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) immunostaining were performed and quantified. At age 7 days, the immature‐to‐mature glomeruli ratio (IMGR) was significantly higher in the STZ group than in the control group. There was no difference in the number of glomeruli between the STZ and control groups; however, the number of glomeruli increased by more than 20% in the control group until 21 days of age, but not in the STZ group. STZ pups showed numerous PCNA‐positive nuclei mainly in tubular cells, but not control pups. At 21 days, eNOS expression in the outer layer of glomerular endothelial nuclei was strong in control pups, but weaker in STZ pups. Treatment with STZ during the early neonatal period disturbs the normal nephrogenesis occurring at this stage of the rodent’s life and causes retardation in renal cortical maturity, as indicated by the increase in both PCNA expression and IMGR, and reduction in eNOS expression.
Liposome‐based diclofenac for the treatment of inflammation in an acute synovitis model in horses
Authors: SCHLEINING J. A. , McCLURE S. R. , EVANS R. B. , HYDE W. G. , WULF L. W. , KIND A. J.
Published: July 2008

Lameness as a result of joint disease is a major source of decreased athletic performance in the horse. Most treatment protocols include the administration of nonsteroidal anti‐inflammatory drugs (NSAIDs). Phenylbutazone, alone or in combination with other treatments, is the most commonly and widely used NSAID, however it has the potential for serious side effects. The introduction of the liposome‐based formulation of the NSAID diclofenac has shown promising effect as a safe and convenient treatment for lameness associated with osteoarthritis. The purpose of this study was to evaluate the effect of topical liposome‐based diclofenac in an acute inflammation model using subjective lameness scores and objective lameness evaluation, carpal surface temperature and circumference, synovial fluid cell count and total protein content, and the biochemical markers interleukin‐1 (IL‐1), IL‐6, and prostaglandin E2as determinants of inflammation. In this acute inflammation model, there was no overall difference between treatment and control groups.
Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model
Authors: TERRITO P. R. , SHANNON H. E. , NEWHALL K. , BARNHART S. D. , PETERS S. C. , ENGLEKING D. R. , BIN T. , BURNETT T. J. , RODEWALD J. M. , ABDUL‐KARIM B. , FREISE K. J.
Published: July 2008

The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration‐time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half‐life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration‐anticonvulsant relationship preclinically in dogs.
Solving cryptogenic histories using host and parasite molecular genetics: the resolution of Littorina littorea's North American origin
Authors: BLAKESLEE APRIL M. H. , BYERS JAMES E. , LESSER MICHAEL P.
Published: July 2008

Even after decades of investigation using multiple sources of evidence, the natural histories of some species remain unclear (i.e. cryptogenic). A key example is Littorina littorea, the most abundant intertidal snail in northeastern North America. Native to Europe, the snail's ecological history in North America has been debated for over 100 years with no definitive resolution. To resolve its cryptogenic status, we used molecular genetics from a novel combination of the snail and a highly associated trematode parasite, Cryptocotyle lingua. Based on mitochondrial sequences of 370 L. littorea and 196 C. lingua individuals, our results demonstrate a significant reduction in genetic diversity in North America vs. Europe, North American haplotypes nested within European haplotypes, and mean divergence estimates of ~500 years ago from Europe for both host and parasite — thus supporting a recent introduction of both host and parasite to North America from Europe. Our study therefore resolves not only a specific cryptogenic history, but it also demonstrates the success of our approach generally and could be used in resolving difficult invasion histories worldwide.
Effective population size dynamics reveal impacts of historic climatic events and recent anthropogenic pressure in African elephants
Authors: OKELLO J. B. A. , WITTEMYER G. , RASMUSSEN H. B. , ARCTANDER P. , NYAKAANA S. , DOUGLAS‐HAMILTON I. , SIEGISMUND H. R.
Published: July 2008

Two hundred years of elephant hunting for ivory, peaking in 1970–1980s, caused local extirpations and massive population declines across Africa. The resulting genetic impacts on surviving populations have not been studied, despite the importance of understanding the evolutionary repercussions of such human‐mediated events on this keystone species. Using Bayesian coalescent‐based genetic methods to evaluate time‐specific changes in effective population size, we analysed genetic variation in 20 highly polymorphic microsatellite loci from 400 elephants inhabiting the greater Samburu‐Laikipia region of northern Kenya. This area experienced a decline of between 80% and 90% in the last few decades when ivory harvesting was rampant. The most significant change in effective population size, however, occurred approximately 2500 years ago during a mid–Holocene period of climatic drying in tropical Africa. Contrary to expectations, detailed analyses of four contemporary age‐based cohorts showed that the peak poaching epidemic in the 1970s caused detectable temporary genetic impacts, with genetic diversity rebounding as juveniles surviving the poaching era became reproductively mature. This study demonstrates the importance of climatic history in shaping the distribution and genetic history of a keystone species and highlights the utility of coalescent‐based demographic approaches in unravelling ancestral demographic events despite a lack of ancient samples. Unique insights into the genetic signature of mid‐Holocene climatic change in Africa and effects of recent poaching pressure on elephants are discussed.