bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of high‐affinity HLA‐DP specific CLIP‐derived peptides in beryllium binding to the HLA‐DPGlu69 berylliosis‐associated molecules and presentation to beryllium‐sensitized T cells
Authors: Amicosante Massimo , Berretta Floriana , Dweik Raed , Saltini Cesare 
Published: December 2008

SummaryBerylliosis is driven by the accumulation in the lung of beryllium‐specific T helper type 1 (Th1) cells recognizing beryllium as antigen when presented principally by human leucocyte antigen DP molecules carrying a glutamate at position β69 (HLA‐DPGlu69). This study was designed to clarify the precise role of peptides in beryllium binding to the HLA‐DP groove’s pocket 4 and to identify peptides with higher affinity for pocket 4 that might prevent beryllium presentation and T‐cell stimulation. Beryllium/HLA‐DP interactions were analysed by the ability of beryllium to compete with CLIP and CLIP‐derived peptides to HLA‐DPGlu69 soluble molecule. The CLIP‐derived low‐affinity peptide CLIP‐AA, could not outcompete beryllium; while the CLIP‐derived high‐affinity peptides CLIP‐YY, CLIP‐QY and CLIP‐RF were only marginally influenced by the presence of beryllium in the competition assay. The effect of these CLIP‐derived high‐affinity peptides on beryllium presentation was determined by measuring interferon‐γ (IFN‐γ) release upon beryllium stimulation of peripheral blood mononuclear cells obtained from beryllium‐hypersensitive subjects. CLIP‐YY did inhibit beryllium presentation and T‐cell activation, while CLIP‐QY and CLIP‐RF markedly enhanced the IFN‐γ response to beryllium. Anti‐HLA‐DP monoclonal antibody blocked the beryllium‐induced IFN‐γ release in the presence of CLIP‐QY (88%) and CLIP‐RF (76%). A similar effect was observed for CLIP‐YY capability to block IFN‐γ release by beryllium stimulation in the presence of CLIP‐QY (79%) and CLIP‐RF (76%). Overall, these data support the proposal that HLA‐DP high‐affinity peptides might be used as a model for specific berylliosis therapy.
Calpain inhibition induces activation of the distinct signalling pathways and cell migration in human monocytes
Authors: Noma Haruyoshi , Kato Takayuki , Fujita Hisakazu , Kitagawa Maki , Yamano Tsunekazu , Kitagawa Seiichi 
Published: December 2008

SummaryWe have recently reported that constitutively active calpain negatively regulates activation of the distinct signalling pathways and cell migration in human neutrophils. Here, we report that a similar regulatory system is also functioning in human monocytes, but not lymphocytes. Calpain was constitutively active in resting human monocytes, but not lymphocytes. Mitogen‐activated protein kinases, including extracellular signal‐regulated kinase (ERK), p38 and c‐Jun N‐terminal kinase (JNK), phosphatidylinositol 3‐kinase (PI3K)/Akt and p21‐activated kinase (PAK, an effector molecule of Rac) were rapidly (within 1 min) activated in monocytes, but not lymphocytes, upon exposure to calpain inhibitors (PD150606 and N‐acetyl‐Leu‐Leu‐Nle‐CHO), but not PD145305 (the inactive analogue of PD150606). Following activation of these signalling pathways, monocytes displayed active migration within 5 min after exposure to calpain inhibitors, and active migration was sustained for more than 45 min. The micropipette method revealed that calpain inhibition‐mediated monocyte migration was chemotaxis, not random migration. The studies with pharmacological inhibitors suggest that calpain inhibition‐mediated monocyte migration is mediated by activation of ERK, p38, JNK, PI3K/Akt and Rac. NSC23766 (Rac inhibitor) and pertussis toxin (PTX) suppressed calpain inhibitor‐induced phosphorylation of distinct signalling molecules (PAK, ERK, p38, JNK and Akt) as well as cell migration, suggesting that the PTX‐sensitive G protein and Rac axis may be a possible key target of calpain inhibitors. These findings suggest that constitutively active calpain negatively regulates activation of the distinct signalling pathways and cell migration in resting monocytes, but not lymphocytes.
Accurate delineation of biogeographical regions depends on the use of an appropriate distance measure
Authors: Gagné Sara A. , Proulx Raphaël 
Published: December 2008

AbstractThe use of analytical techniques to delineate biogeographical regions is becoming increasingly popular. One recent example, Heikinheimo et al. (Journal of Biogeography, 2007, 34, 1053–1064), applied the k‐means clustering algorithm to define the biogeography of the European land mammal fauna. However, they used the Euclidean distance measure to cluster grid cells described by species‐occurrence data, which is inappropriate. The Euclidian distance yields misleading results when applied to species‐occurrence data because of the double‐zero problem and the species‐abundance paradox. We repeat their analysis using the Hellinger distance, a measure appropriate for species‐occurrence data and which has been shown to outperform other such measures. Our results differ substantially from those presented by Heikinheimo et al. We argue that the rigorous application of appropriate statistical techniques is of crucial concern within conservation biogeography.
Improved outcome in Wegener’s granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts
Authors: Eriksson P. , Jacobsson L. , Lindell Å. , Nilsson J.‐Å. , Skogh T. 
Published: December 2008

Abstract.Objectives.  Mortality rates for Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined.Design.  Survival analyses were performed by Kaplan–Meier survival curves, SMR and proportional hazards regression models.Setting.  The nephrology and rheumatology clinics at Linköping University Hospital, Sweden.Subjects.  All patients diagnosed with WG or MPA in the catchment area during 1978–2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996.Results.  The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 μmol L−1 (16% dialysis‐dependent) vs. 192 μmol L−1 (5% dialysis‐dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43–6.09) and 1.6 (95% CI: 0.6–3.2) in the recent cohort and 5.2 (95% CI: 1.07–15.14) and 2.5 (95% CI: 0.93–5.52) in the old cohort. Five‐year survival was 87% and 81%. Serum creatinine, age, end‐stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death.Conclusion.  Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.
Genetics, behaviour and chemical recognition of the invading ant Pheidole megacephala
Authors: FOURNIER DENIS , DE BISEAU JEAN‐CHRISTOPHE , ARON SERGE 
Published: December 2008

AbstractIntroduced species often become ecologically dominant, displacing native species and posing a serious threat to ecosystem function and global biodiversity. Ants are among the most widespread and damaging alien species; introductions are often accompanied by population‐level behavioural and genetic changes contributing to their success. We investigated the genetic structure, chemical profile and nestmate recognition in introduced populations of the invasive big‐headed ant, Pheidole megacephala, in Australia. Behavioural analyses show that workers are not aggressive towards conspecifics from different nests, even at large geographical scales (up to 3000 km) and between populations encompassing a wide range of environmental conditions. By contrast, interactions with workers of other species invariably result in agonistic behaviours. Genetic analyses reveal that populations have low genetic diversity. No genetic differentiation occurs among nests of the same population; differentiation between populations, though significant, remains weak. Chemical analyses indicate that cuticular lipids are similar between colonies of a population, and that differentiation between populations is low. Altogether, these results indicate that the big‐headed ant P. megacephala forms a large unicolonial population across northern/eastern Australia.
High genetic diversity and connectivity in the polyploid invasive seaweedAsparagopsis taxiformis(Bonnemaisoniales) in the Mediterranean, explored with microsatellite alleles and multilocus genotypes
Authors: ANDREAKIS NIKOS , KOOISTRA WIEBE H. C. F. , PROCACCINI GABRIELE 
Published: December 2008

AbstractThe red alga,Asparagopsis taxiformis, has recently expanded its distribution range into the Western Mediterranean Sea, and populations have now even been found on the Portuguese South coast. All Western Mediterranean populations belong to a single mitochondrial cryptic lineage (referred to as lineage 2 in earlier studies) and probably result from a recent invasion of Indo‐Pacific origin. Here we investigate fine‐scale population genetic diversity and structure within and among Mediterranean populations of lineage 2 using eight microsatellite loci and compare the obtained patterns with those observed in a Californian population of the same lineage. To generate an appropriate analytical method suitable to the polyploid status of this species, we score microsatellite loci as in a dominant marker system. Thereafter, we produce robust descriptors inferred from frequencies of both microsatellite alleles and multilocus genotypes. Populations from California and the Mediterranean Sea differ considerably in their levels of genetic diversity. In the Mediterranean, populations reproduce predominantly sexually and exhibit high levels of genotypic variation, suggestive either of multiple introductions or of a single introduction by a genetically diverse and large group of individuals. Bayesian clustering revealed one or possibly two weakly supported panmictic subpopulations, indicative of extensive admixture. The expansion of this lineage is rapid, possibly due to the absence of eco–physiological barriers to gene flow throughout its invasive trajectory.
Molecular genetic data provide support for a model of transmission dynamics in an Australian reptile tick, Bothriocroton hydrosauri
Authors: GUZINSKI JARO , BULL C. MICHAEL , DONNELLAN STEPHEN C. , GARDNER MICHAEL G. 
Published: December 2008

Abstract Bothriocroton hydrosauri is a three‐host ixodid tick that infests large reptiles in southeastern Australia, where its most common host is a large scincid lizard Tiliqua rugosa. Based on previous ecological and behavioural studies of this system, we propose a ‘ripple’ model of tick population dynamics, where only a few female ticks succeed in producing surviving offspring. These females then are the centres of ripples of their progeny spreading into the broader landscape. The model predicts higher relatedness among larvae than among nymphs or adults on a host, and significant spatial autocorrelation in larvae extending further than for the later life stages. The model also predicts that adult ticks are likely to encounter related partners and that this will generate inbreeding within the population. We tested those predictions using nine polymorphic microsatellite loci on a sample of 848 ticks (464 larvae, 140 nymphs and 244 adults) collected from 98 lizard hosts from near Bundey Bore Station in South Australia. Our data support the predictions and indicate that the dynamics of transmission among hosts play an important role in parasite population structure.
Statistical hypothesis testing in intraspecific phylogeography: nested clade phylogeographical analysis vs. approximate Bayesian computation
Authors: TEMPLETON ALAN R. 
Published: December 2008

AbstractNested clade phylogeographical analysis (NCPA) and approximate Bayesian computation (ABC) have been used to test phylogeographical hypotheses. Multilocus NCPA tests null hypotheses, whereas ABC discriminates among a finite set of alternatives. The interpretive criteria of NCPA are explicit and allow complex models to be built from simple components. The interpretive criteria of ABC are ad hoc and require the specification of a complete phylogeographical model. The conclusions from ABC are often influenced by implicit assumptions arising from the many parameters needed to specify a complex model. These complex models confound many assumptions so that biological interpretations are difficult. Sampling error is accounted for in NCPA, but ABC ignores important sources of sampling error that creates pseudo‐statistical power. NCPA generates the full sampling distribution of its statistics, but ABC only yields local probabilities, which in turn make it impossible to distinguish between a good fitting model, a non‐informative model, and an over‐determined model. Both NCPA and ABC use approximations, but convergences of the approximations used in NCPA are well defined whereas those in ABC are not. NCPA can analyse a large number of locations, but ABC cannot. Finally, the dimensionality of tested hypothesis is known in NCPA, but not for ABC. As a consequence, the ‘probabilities’ generated by ABC are not true probabilities and are statistically non‐interpretable. Accordingly, ABC should not be used for hypothesis testing, but simulation approaches are valuable when used in conjunction with NCPA or other methods that do not rely on highly parameterized models.
Amino acid 310 determines the donor substrate specificity of serogroup W‐135 and Y capsule polymerases of Neisseria meningitidis
Authors: Claus Heike , Stummeyer Katharina , Batzilla Julia , Mühlenhoff Martina , Vogel Ulrich 
Published: December 2008

SummaryThe capsular polysaccharides of serogroup W‐135 and Y meningococci are sialic acid‐containing heteropolymers, with either galactose or glucose as the second sugar residue. As shown previously, sequences of the predicted enzymes that catalyse capsule polymerization, i.e. SiaDW‐135 and SiaDY, differ in only a few amino acids. By in vitro assays with purified recombinant proteins, SiaDW‐135 and SiaDY were now confirmed to be the capsule polymerases harbouring both hexosyltransferase and sialyltransferase activity. In order to identify amino acids crucial for substrate specificity of the capsule polymerases, polymorphic sites were narrowed down by DNA sequence comparisons and subsequent site‐directed mutagenesis. Serogroup‐specific amino acids were restricted to the N‐terminal part of the proteins. Exclusively amino acid 310, located within the nucleotide recognition domain of the enzymes' predicted hexosyltransferase moiety, accounted for substrate specificity as shown by immunochemistry and in vitro activity assay. Pro‐310 determined galactosyltransferase activity that resulted in a serogroup W‐135 capsule and Gly‐310 determined glucosyltransferase activity that resulted in a serogroup Y capsule. In silico analysis revealed a similar amino acid‐based association in other members of the same glycosyltransferase family irrespective of the bacterial species.
Genome‐wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis
Authors: Sala Claudia , Haouz Ahmed , Saul Frederick A. , Miras Isabelle , Rosenkrands Ida , Alzari Pedro M. , Cole Stewart T. 
Published: December 2008

SummaryComparative genomics with Staphylococcus aureus suggested the existence of a regulatory system governing beta‐lactamase (BlaC) production in Mycobacterium tuberculosis. The crystal structure of Rv1846c, a winged helix regulator of previously unknown function, was solved thus revealing strong similarity to the BlaI and MecI repressors of S. aureus, which both respond to beta‐lactam treatment. Using chromatin immunoprecipitation and hybridization to microarrays (ChIP‐on‐chip), the Rv1846c regulon was shown to comprise five separate genomic loci. Two of these mediate responses and resistance to beta‐lactam antibiotics (rv1845c, rv1846c–rv1847; blaC–sigC); two encode membrane proteins of unknown function (rv1456c, rv3921c) while the last codes for ATP synthase (rv1303–atpBEFHAGDC–rv1312). The ChIP‐on‐chip findings were confirmed independently using electrophoretic mobility shift assays, DNAse footprinting and transcript analysis leading to Rv1846c being renamed BlaI. When cells were treated with beta‐lactams, BlaI was released from its operator sites causing derepression of the regulon and upregulation of ATP synthase transcription. The existence of a potential regulatory loop between cell wall integrity and ATP production was previously unknown.
DnaA protein interacts with RNA polymerase and partially protects it from the effect of rifampicin
Authors: Flåtten Ingvild , Morigen  , Skarstad Kirsten 
Published: December 2008

SummaryThe Escherichia coli DnaA protein forms an oligomer at the origin and initiates chromosome replication with the aid of architectural elements and transcription by RNA polymerase. Rifampicin inhibits initiation of transcription by RNA polymerase and thus also initiation of replication. Here, we report that wild‐type cells undergo rifampicin‐resistant initiation of replication during slow growth in acetate medium. The rifampicin‐resistant initiation was prevented by reducing the availability of DnaA. In vitro experiments showed that the DnaA protein interacted with RNA polymerase and that it afforded a partial protection from the negative effect of rifampicin. It is possible that rifampicin‐resistant rounds of replication occur when a surplus of DnaA is available at the origin. In rich medium wild‐type cells do not exhibit rifampicin‐resistant rounds of replication, possibly indicating that there is no surplus DnaA, and that DnaA activity is the factor limiting the process of initiation. During growth in acetate medium, on the contrary, DnaA activity is not limiting in the same way because an initiation potential is present and can be turned into extra rounds of replication when rifampicin is added. The result suggests that regulation of replication initiation may differ at different growth rates.
The role of the Mediterranean region in the development of sedimentary geology: a historical overview
Authors: FISCHER ALFRED G. , GARRISON ROBERT E. 
Published: December 2008

AbstractThe Mediterranean region, source of so much knowledge in the world, is the site of major advances in sedimentary geology. In addition to its economic and cultural richness, the geological and geographic diversity of the region, plus its active geological processes, have long stimulated indigenous scholars, along with attracting talented outsiders such as Steno, Lyell, Walther, Kuenen and Bagnold. Since classical Hellenic times, debates about the origin of fossils and the changing positions of sea‐level served as catalysts for studies of sediments, sedimentary rocks and ancient life. The presence of geologically young and easily interpreted marine shell beds in many Mediterranean coastal areas adjacent to their modern analogues was a particular stimulus for progress in sedimentary geology, for example, the very advanced stratigraphic ideas of Leonardo da Vinci, expressed solely in his unpublished notebooks. Impeding progress was the geological complexity of facies, faunas and structure in the circum‐Mediterranean Alpine belts. Once the secrets of these were unlocked, however, the Mediterranean region became the source of major discoveries about syn‐sedimentary tectonics, carbonate platforms, pelagic and anoxic sediments, turbidites, evaporites, aeolian processes, cyclostratigraphy, magnetic stratigraphy and impact events. In many of these Mediterranean discoveries, the critical element is the occurrence of extensive Mesozoic‐Cenozoic pelagic successions whose precise age dating was made possible by pioneering biostratgraphic studies using microfossils.
Controls on clastic sequence geometries in a shallow‐marine, transtensional basin: the Bohemian Cretaceous Basin, Czech Republic
Authors: ULIČNÝ DAVID , LAURIN JIŘÍ , ČECH STANISLAV 
Published: December 2008

AbstractThe Bohemian Cretaceous Basin combines features of a shallow‐water (mostly < 100 m) epicontinental seaway formed during a global transgression with those of a tectonically active, transtensional setting. The basin formed under a greenhouse climate and was affected by strong axial currents. Dense well‐log coverage, combined with locally high‐quality exposures and biostratigraphic control, make it possible to examine in three dimensions the geometries of genetic sequences and interpret their controlling variables. Sand‐dominated deltas formed sequences at several spatial scales that reflect nested transgressive–regressive cycles with durations ranging from tens of thousands of years to millions of years. Progradation directions and distances, thicknesses and internal geometry of the individual sequences were controlled primarily by intrabasinal faulting, basin‐scale changes in subsidence rate, eustatic fluctuations and localized bathymetric changes due to successive filling of the basin. Along‐strike change in sediment input from different parts of the source area and a short‐lived uplift of a secondary clastic source provided additional controls on the sequence geometry. Efficient hypopycnal transport combined with redeposition of fine clastics in shallow water promoted development of steep slopes of sand‐dominated deltas while preventing downlap of muddy clinoforms; most of the suspended load became deposited downcurrent in subhorizontal or gently dipping bottomsets. Long‐term accommodation rates were low during the Early to Middle Turonian, with minor intrabasinal faulting, but became accelerated in the Late Turonian and Early Coniacian. This acceleration was caused at least partly by increased subsidence rate accompanied by structural partitioning of the depocentre and partly compensated by increased sediment input indicating increased uplift rates in the Western Sudetic Island source area. This event probably reflected an increase in the regional strain rate in Central Europe. The succession of two major flooding events in the Early Turonian and late Early Coniacian, separated by a low‐accommodation interval in the Middle Turonian, shows a close similarity to published estimates of long‐term eustatic curves. However, the eustatic component of accommodation rate in the Bohemian Late Turonian and Coniacian is difficult to separate from accelerated subsidence. In several cases, evidence for short‐term (100 kyr scale) forced regressions, independent of basinal structural activity, suggests small‐scale eustatic falls at rates which, as presently understood, cannot be explained other than by a glacio‐eustatic mechanism.