bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virulence determinants in a natural butterfly-parasite system
Authors: de ROODE J. C. , GOLD L. R. , ALTIZER S. 
Published: December 2006

SUMMARYMuch evolutionary theory assumes that parasite virulence (i.e. parasite-induced host mortality) is determined by within-host parasite reproduction and by the specific parasite genotypes causing infection. However, many other factors could influence the level of virulence experienced by hosts. We studied the protozoan parasite Ophryocystis elektroscirrha in its host, the monarch butterfly, Danaus plexippus. We exposed monarch larvae to wild-isolated parasites and assessed the effects of within-host replication and parasite genotype on host fitness measures, including pre-adult development time and adult weight and longevity. Per capita replication rates of parasites were high, and infection resulted in high parasite loads. Of all host fitness traits, adult longevity showed the clearest relationship with infection status, and decreased continuously with increasing parasite loads. Parasite genotypes differed in their virulence, and these differences were maintained across ecologically relevant variables, including inoculation dose, host sex and host age at infection. Thus, virulence appears to be a robust genetic parasite trait in this system. Although parasite loads and genotypes had strong effects on virulence, inoculation dose, host sex and age at infection were also important. These results have implications for virulence evolution and emphasize the need for a detailed understanding of specific host-parasite systems for addressing theory.
Neuropeptide Y modulates effects of bradykinin and prostaglandin E2 on trigeminal nociceptors via activation of the Y1 and Y2 receptors
Authors: Gibbs J L , Diogenes A , Hargreaves K M 
Published: December 2006

Background and Purpose:Although previous studies have demonstrated that neuropeptide Y (NPY) modulates nociceptors, the relative contributions of the Y1 and Y2 receptors are unknown. Therefore, we evaluated the effect of Y1 and Y2 receptor activation on nociceptors stimulated by bradykinin (BK) and prostaglandin E2 (PGE2).Experimental approach:Combined immunohistochemistry (IHC) with in situ hybridization (ISH) demonstrated that Y1‐ and Y2‐receptors are collocated with bradykinin 2 (B2)‐receptors in rat trigeminal ganglia (TG). The relative functions of the Y1 and Y2 receptors in modulating BK/PGE2‐evoked CGRP release and increased intracellular calcium levels in cultured TG neurons were evaluated.Key results:The Y1 and Y2 receptors are co‐expressed with B2 in TG neurons, suggesting the potential for direct NPY modulation of BK responses. Pretreatment with the Y1 agonist [Leu31,Pro34]‐NPY, inhibited BK/PGE2‐evoked CGRP release. Conversely, pretreatment with PYY(3‐36), a Y2 agonist, increased BK/PGE2 evoked CGRP release. Treatment with NPY evoked an overall inhibitory effect, although of lesser magnitude. Similarly, [Leu31,Pro34]‐NPY inhibited BK/PGE2‐evoked increases in intracellular calcium levels whereas PYY(3‐36) increased responses. NPY inhibition of BK/PGE2‐evoked release of CGRP was reversed by the Y1 receptor antagonist, BIBO3304, and higher concentrations of BIBO3304 significantly facilitated CGRP release. The Y2 receptor antagonist, BIIE0246, enhanced the inhibitory NPY effects.Conclusions and implications:These results demonstrate that NPY modulation of peptidergic neurons is due to net activation of inhibitory Y1 and excitatory Y2 receptor systems. The relative expression or activity of these opposing receptor systems may mediate dynamic responses to injury and pain.British Journal of Pharmacology (2007) 150, 72–79. doi:10.1038/sj.bjp.0706967
Lack of selectivity of URB602 for 2‐oleoylglycerol compared to anandamide hydrolysis in vitro
Authors: Vandevoorde S , Jonsson K‐O , Labar G , Persson E , Lambert D M , Fowler C J 
Published: December 2006

Background and purpose:Two compounds, URB602 and URB754, have been reported in the literature to be selective inhibitors of monoacylglycerol lipase, although a recent study has questioned their ability to prevent 2‐arachidonoyl hydrolysis by brain homogenates and cerebellar membranes. In the present study, the ability of these compounds to inhibit monoacylglycerol lipase and fatty acid amide hydrolase has been reinvestigated.Experimental approach:Homogenates and cell lines were incubated with test compounds and, thereafter, with either [3H]‐2‐oleoylglycerol or [3H]‐anandamide. Labelled reaction products were separated from substrate using chloroform: methanol extraction.Key results:In cytosolic fractions from rat brain, URB602 and URB754 inhibited the hydrolysis of 2‐oleoylglycerol with IC50 values of 25 and 48 μM, respectively. Anandamide hydrolysis by brain membranes was not sensitive to URB754, but was inhibited by URB602 (IC50 value 17 μM). Hydrolysis of 2‐oleoylglycerol by human recombinant monoacylglycerol lipase was sensitive to URB602, but not URB754. The lack of selectivity of URB602 for 2‐oleoylglycerol compared to anandamide hydrolysis was also observed for intact RBL2H3 basophilic leukaemia cells. C6 glioma expressed mRNA for monoacylglycerol lipase, and hydrolyzed 2‐oleoylglycerol in a manner sensitive to inhibition by methyl arachidonoyl fluorophosphonate but not URB754 or URB597. MC3T3‐E1 mouse osteoblastic cells, which did not express mRNA for monoacylglycerol lipase, hydrolyzed 2‐oleoylglycerol in the presence of URB597, but the hydrolysis was less sensitive to methyl arachidonoyl fluorophosphonate than for C6 cells.Conclusions and implications:The data demonstrate that the compounds URB602 and URB754 do not behave as selective and/or potent inhibitors of monoacylglycerol lipase.British Journal of Pharmacology (2007) 150, 186–191. doi:10.1038/sj.bjp.0706971
A Boy With Proximal Weakness and Cardiomyopathy
Authors: Mitchell Christopher W , Bertorini Tulio E , Shadle Mariallan 
Published: December 2006

Educational Objectives:
1) To present an adolescent patient with proximal weakness and cardiomyopathy and discuss the differential diagnosis. 2) To appreciate cardiac involvement in a subset of myopathic disorders.

Key Questions:
1) What is the differential diagnosis for an adolescent with proximal muscle weakness and cardiomyopathy? 2) What is the diagnostic workup for this patient? 3) What is the management of a patient with this disorder?
Mechanical deformation model of the western United States instantaneous strain-rate field
Authors: Pollitz Fred F. , Vergnolle Mathilde 
Published: December 2006

SummaryWe present a relationship between the long-term fault slip rates and instantaneous velocities as measured by Global Positioning System (GPS) or other geodetic measurements over a short time span. The main elements are the secularly increasing forces imposed by the bounding Pacific and Juan de Fuca (JdF) plates on the North American plate, viscoelastic relaxation following selected large earthquakes occurring on faults that are locked during their respective interseismic periods, and steady slip along creeping portions of faults in the context of a thin-plate system. In detail, the physical model allows separate treatments of faults with known geometry and slip history, faults with incomplete characterization (i.e. fault geometry but not necessarily slip history is available), creeping faults, and dislocation sources distributed between the faults. We model the western United States strain-rate field, derived from 746 GPS velocity vectors, in order to test the importance of the relaxation from historic events and characterize the tectonic forces imposed by the bounding Pacific and JdF plates. Relaxation following major earthquakes (Mγ 8.0) strongly shapes the present strain-rate field over most of the plate boundary zone. Equally important are lateral shear transmitted across the Pacific–North America plate boundary along ∼1000 km of the continental shelf, downdip forces distributed along the Cascadia subduction interface, and distributed slip in the lower lithosphere. Post-earthquake relaxation and tectonic forcing, combined with distributed deep slip, constructively interfere near the western margin of the plate boundary zone, producing locally large strain accumulation along the San Andreas fault (SAF) system. However, they destructively interfere further into the plate interior, resulting in smaller and more variable strain accumulation patterns in the eastern part of the plate boundary zone. Much of the right-lateral strain accumulation along the SAF system is systematically underpredicted by models which account only for relaxation from known large earthquakes. This strongly suggests that in addition to viscoelastic-cycle effects, steady deep slip in the lower lithosphere is needed to explain the observed strain-rate field.
Stress transfer relations among the earthquakes that occurred in Kerman province, southern Iran since 1981
Authors: Nalbant Suleyman S. , Steacy Sandy , McCloskey John 
Published: December 2006

SummaryWe explore the possible stress triggering relationship of the M≥ 6.4 earthquakes that occurred in Kerman Province, southern Iran since 1981. We calculated stress changes due to both coseismic sudden movement in the upper crust and the time-dependent viscous relaxation of the lower crust and/or upper mantle following the event. Four events of M≥ 6.4 occurred between 1981 and 2005, on and close to the Gowk fault, show a clear Coulomb stress load to failure relationship. The 2003 M= 6.5 Bam earthquake, however, which occurred approximately 95 km SW of the closest Gowk event, shows a very weak stress relation to preceding earthquakes. The coseismic static stress change at the hypocentre of the Bam earthquake is quite small (∼0.006 bars). The time-dependent post-seismic stress change could be 26 times larger or 7 times lower than that of coseismic static stress alone depending on the choice of viscoelastic crustal model and the effective coefficient of friction. Given the uncertainties in the viscoelastic earth models and the effective coefficient of friction, we cannot confidently conclude that the 2003 Bam event was brought closer to failure through coseismic or post-seismic stress loading. Interestingly, the southern Gowk segment with a similar strike to that of the Bam fault, experienced a stress load of up to 8.3 bars between 1981 and 2003, and is yet to have a damaging earthquake.
Isolated lymphoid follicle maturation induces the development of follicular dendritic cells
Authors: Glaysher Bridget R. , Mabbott Neil A. 
Published: December 2006

SummaryIsolated lymphoid follicles (ILFs) are recently identified lymphoid structures in the small intestine with features similar to Peyer's patches (PPs). Using immunohistochemistry we characterized the composition of ILFs in the small intestines of immunocompetent mice and of mice that lacked PPs as a result of either genetic deficiency of lymphotoxin or temporary in utero lymphotoxin‐β receptor‐signalling blockade. We showed that although both immature and mature ILFs were present in the intestines of immunocompetent mice, PP‐deficiency induced a significantly greater number of mature ILFs. We found that in addition to B‐lymphocyte‐containing germinal centres, mature ILFs also possessed large networks of follicular dendritic cells (FDCs). These features were not detected within immature ILFs. Indeed, the presence of FDCs could be used to reliably distinguish ILF maturity. Further analysis revealed that the area occupied by the FDCs within mature ILFs was substantial. The total area occupied by FDCs in all the mature ILFs in mice lacking PPs was equivalent to the total area occupied by FDCs in all the PPs and the few mature ILFs in immunocompetent mice. Based on these data we reasoned that in the absence of PPs, mature ILFs are important inductive sites for intestinal immune responses. Indeed, in mice that lacked PPs, ILF maturation coincided with a restoration of faecal immunoglobulin A levels to values that were comparable to those found in immunocompetent mice. Taken together, these data imply that the induction of germinal centres and FDC networks within mature ILFs in response to PP deficiency provides an important compensatory mechanism.
Cryptic behaviours, inverse genetic landscapes, and spatial avoidance of inbreeding in the Pacific jumping mouse
Authors: VIGNIERI SACHA N. 
Published: December 2006

AbstractAlthough the behaviour of individuals is known to impact the genetic make‐up of a population, observed behavioural patterns do not always correspond to patterns of genetic structure. In particular, philopatric or dispersal‐limited species often display lower‐than‐expected values of relatedness or inbreeding suggestive of the presence of cryptic migration, dispersal, or mating behaviours. I used a combination of microsatellite and mark–recapture data to test for the influence of such behaviours in a dispersal‐limited species, the Pacific jumping mouse, within a semi‐isolated population over three seasons. Despite short dispersal distances and a low rate of first generation migrants, heterozygosities were high and inbreeding values were low. Dispersal was male‐biased; interestingly however, this pattern was only present when dispersal was considered to include movement away from paternal home range. Not unexpectedly, males were polygynous; notably, some females were also found to be polyandrous, selecting multiple neighbouring mates for their single annual litter. Patterns of genetic structure were consistent with these more inconspicuous behavioural patterns. Females were more closely related than males and isolation by distance was present only in females. Furthermore, detailed genetic landscapes revealed the existence of strong, significant negative correlations, with areas of low genetic distance among females overlapping spatially with areas of high genetic distance among males. These results support the hypothesis that the detected cryptic components of dispersal and mating behaviour are reducing the likelihood of inbreeding in this population through paternally driven spatial mixing of male genotypes and polyandry of females.
Phylogeography and population history of the crab‐eating fox (Cerdocyon thous)
Authors: TCHAICKA LIGIA , EIZIRIK EDUARDO , DE OLIVEIRA TADEU G. , CÂNDIDO JOSÉ FLÁVIO , FREITAS THALES R. O. 
Published: December 2006

AbstractThe crab‐eating fox is a medium‐sized Neotropical canid with generalist habits and a broad distribution in South America. We have investigated its genetic diversity, population structure and demographic history across most of its geographic range by analysing 512 base pairs (bp) of the mitochondrial DNA (mtDNA) control region, 615 bp of the mtDNA cytochrome b gene and 1573 total nucleotides from three different nuclear fragments. MtDNA data revealed a strong phylogeographic partition between northeastern Brazil and other portions of the species’ distribution, with complete separation between southern and northern components of the Atlantic Forest. We estimated that the two groups diverged from each other c. 400 000–600 000 years ago, and have had contrasting population histories. A recent demographic expansion was inferred for the southern group, while northern populations seem to have had a longer history of large population size. Nuclear sequence data did not support this north–south pattern of subdivision, likely due at least in part to secondary male‐mediated historical gene flow, inferred from multilocus coalescent‐based analyses. We have compared the inferred phylogeographic patterns to those observed for other Neotropical vertebrates, and report evidence for a major north–south demographic discontinuity that seems to have marked the history of the Atlantic Forest biota.
The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium
Authors: Sittka Alexandra , Pfeiffer Verena , Tedin Karsten , Vogel Jörg 
Published: December 2006

SummaryThe RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Qβ RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium. A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro. Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non‐coding RNAs, placing Hfq at the centre of post‐transcriptional regulation of virulence gene expression in Salmonella. In addition, the hfq mutation appears to cause a chronic activation of the RpoE‐mediated envelope stress response which is likely due to a misregulation of membrane protein expression.
Mutations in transmembrane domains 1, 4 and 9 of thePlasmodium falciparumchloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine
Authors: Cooper Roland A. , Lane Kristin D. , Deng Bingbing , Mu Jianbing , Patel Jigar J. , Wellems Thomas E. , Su Xinzhuan , Ferdig Michael T. 
Published: December 2006

SummaryMutations in thePlasmodium falciparumchloroquine (CQ) resistance transporter (PfCRT) can result in verapamil‐reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane‐spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of theP. falciparum106/1K76parasite line, we used single‐step drug selection to generate isogenic clones containing uniquepfcrtpoint mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I and K76T) and 9 (Q352K, Q352R). The resulting changes of charge and hydropathy affected quantitative CQ susceptibility and accumulation as well as the stereospecific responses to quinine and quinidine. These results, together with a previously described S163R mutation in transmembrane domain 4, indicate that transmembrane segments 1, 4 and 9 of PfCRT provide important structural components of a substrate recognition and translocation domain. Charge‐affecting mutations within these segments may affect the ability of PfCRT to bind different quinoline drugs and determine their net accumulation in the DV.
A fail‐safe system for the ribosome under zinc‐limiting conditions inBacillus subtilis
Authors: Natori Yousuke , Nanamiya Hideaki , Akanuma Genki , Kosono Saori , Kudo Toshiaki , Ochi Kozo , Kawamura Fujio 
Published: December 2006

SummaryAs zinc is an essential trace metal ion for all living cells, cells elaborate a variety of strategies to cope with zinc starvation. InBacillus subtilis, genes encoding ribosomal proteins L31 and S14 are duplicated into two types: one type contains a zinc‐binding motif (RpmE or RpsN), whereas the other does not (YtiA or YhzA). We have previously shown that displacement of RpmE (L31) by YtiA from already assembled ribosomes is controlled by zinc, and this replacement could contribute to zinc mobilization under zinc‐limiting conditions. We propose here that the switch between the two types of S14 has a different significance.rpsNis indispensable for growth and depletion of RpsN results in defective 30S subunits. YhzA can functionally replace RpsN to allow continued ribosome assembly under zinc‐limiting conditions. Unlike YtiA, YhzA appeared in the ribosome at a slower rate consistent with incorporation into newly synthesized, rather than pre‐existing ribosomes. These results raise the possibility that YhzA is involved in a fail‐safe system for thede novosynthesis of ribosomes under zinc‐limiting conditions.
NifX and NifEN exchange NifB cofactor and the VK‐cluster, a newly isolated intermediate of the iron‐molybdenum cofactor biosynthetic pathway
Authors: Hernandez Jose A. , Igarashi Robert Y. , Soboh Basem , Curatti Leonardo , Dean Dennis R. , Ludden Paul W. , Rubio Luis M. 
Published: December 2006

SummaryThe iron‐molybdenum cofactor of nitrogenase (FeMo‐co) is synthesized in a multistep process catalysed by several Nif proteins and is finally inserted into a pre‐synthesized apo‐dinitrogenase to generate mature dinitrogenase protein. The NifEN complex serves as scaffold for some steps of this synthesis, while NifX belongs to a family of small proteins that bind either FeMo‐co precursors or FeMo‐co during cofactor synthesis. In this work, the binding of FeMo‐co precursors and their transfer between purified Azotobacter vinelandii NifX and NifEN proteins was studied to shed light on the role of NifX on FeMo‐co synthesis. Purified NifX binds NifB cofactor (NifB‐co), a precursor to FeMo‐co, with high affinity and is able to transfer it to the NifEN complex. In addition, NifEN and NifX exchange another [Fe‐S] cluster that serves as a FeMo‐co precursor, and we have designated it as the VK‐cluster. In contrast to NifB‐co, the VK‐cluster is electronic paramagnetic resonance (EPR)‐active in the reduced and the oxidized states. The NifX/VK‐cluster complex is unable to support in vitro FeMo‐co synthesis in the absence of NifEN because further processing of the VK‐cluster into FeMo‐co requires the simultaneous activities of NifEN and NifH. Our in vitro studies suggest that the role of NifX in vivo is to serve as transient reservoir of FeMo‐co precursors and thus help control their flux during FeMo‐co synthesis.
The major chemotaxis gene cluster of Rhizobium leguminosarum bv. viciae is essential for competitive nodulation
Authors: Miller Lance D. , Yost Christopher K. , Hynes Michael F. , Alexandre Gladys 
Published: December 2006

SummaryRhizobium leguminosarum biovar viciae strain 3841 is a motile alpha‐proteobacterium that can establish a nitrogen‐fixing symbiosis within the roots of pea plants. In order to determine the contribution of chemotaxis to the lifestyle of R. leguminosarum, we have characterized the function of two chemotaxis gene clusters (che1 and che2) in controlling motility behaviour. We have found that both chemotaxis gene clusters modulate the motility swimming bias of R. leguminosarum cells and that the che1 cluster is the major pathway controlling swimming bias and chemotaxis. The che2 cluster also contributes to swimming bias, but has a minor effect on chemotaxis. Using competitive nodulation assays, we have demonstrated that a functional che1 cluster, but not the che2 cluster, promotes competitive nodulation of the peas. This finding implies that the environmental cue(s) triggering chemotaxis of R. leguminosarum bv. viciae cells towards the roots of pea and facilitating colonization are likely to be processed through the che1 cluster despite the contribution of both che clusters to swimming behaviour. A phylogenetic analysis of the distribution of che1 and che2 orthologues in the alpha‐proteobacteria together with our results allow us to propose that che1 homologues are major controllers of chemotaxis and host association in the Rhizobiaceae.