bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and functional defects of dendritic cells derived from the MUTZ‐3 leukaemia line
Authors: Rasaiyaah Jane , Noursadeghi Mahdad , Kellam Paul , Chain Benjamin 
Published: November 2008

SummaryDendritic cells (DC) generated from MUTZ‐3, an immortalized acute myeloid leukaemia‐derived cell line, have potential application as a model for the study of human DC, and as a tool with which to stimulate immunotherapeutic responses to cancer. However, the relationship of MUTZ‐3 DC to their non‐transformed counterparts remains incompletely understood. Immunoselected CD14+ MUTZ‐3 cells were used to generate a homogeneous population of DC (M3DC). These cells had a cell surface phentoype and morphology characteristic of conventional monocyte‐derived DC (MDDC). Whole genome transcriptome comparison of M3DC and MDDC however, revealed extensive differences between these two cell types. Functional ontology‐based data analysis revealed three enriched clusters of genes downregulated in M3DC, with functions in pathogen recognition, DC maturation and cytokine/chemokine signalling. Downregulation of protein expression was confirmed for several of these genes. The molecular differences were accompanied by a profoundly impaired phenotypic and functional response of M3DC to microbial stimulation. The immortalized phenotype of MUTZ‐3 therefore reflects not only deregulated proliferative capacity, but substantial perturbation of normal antigen‐presenting cell function. These results have important implications for studies using MUTZ‐3 as a model of MDDC or for cancer immunotherapy.
Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti‐HLA antibodies
Authors: Apps Richard , Murphy Shawn P. , Fernando Raymond , Gardner Lucy , Ahad Tashmeeta , Moffett Ashley 
Published: November 2008

SummaryHuman trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class‐I (HLA‐I) loci has made it difficult to generate locus‐specific monoclonal antibodies (mAbs). The problem of defining an antibody’s reactivity against the thousands of existing HLA‐I allotypes has often made it impossible to determine the HLA bound by a mAb in biological samples from a normal outbred population. Here we have used commercially available beads coated with individual HLA‐I to characterize experimentally the reactivity of nine mAb against 96 common HLA‐I allotypes. In conjunction with donor HLA‐I genotyping, we could then define the specific HLA molecules bound by these antibodies in normal individuals. We used this approach to analyse the HLA expression of primary trophoblast cells from normal pregnancies; the choriocarcinoma cells JEG‐3 and JAR; and the placental cell lines HTR‐8/SVneo, Swan‐71 and TEV‐1. We confirm that primary villous trophoblast cells are HLA null whereas extravillous trophoblast cells express HLA‐C, HLA‐G and HLA‐E, but not HLA‐A, HLA‐B or HLA‐DR molecules in normal pregnancy. Tumour‐derived JEG‐3 and JAR cells reflect extravillous and villous trophoblast HLA phenotypes, respectively, but the HLA repertoire of the in vitro derived placental cell lines is not representative of either in vivo trophoblast phenotype. This study raises questions regarding the validity of using the placental cell lines that are currently available as model systems for immunological interactions between fetal trophoblast and maternal leucocytes bearing receptors for HLA molecules.
Elevation of interleukin‐18 in chronic hepatitis C: implications for hepatitis C virus pathogenesis
Authors: Sharma Arpita , Chakraborti Anuradha , Das Ashim , Dhiman Radha Krishan , Chawla Yogesh 
Published: November 2008

SummaryThe outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)‐18, an interferon‐γ‐inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL‐18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL‐18 in the pathogenesis and persistence of HCV. IL‐18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL‐18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL‐18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL‐18 concentrations were related to the Child–Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL‐18 levels with histological activity score and necrosis. IL‐18 mRNA expression was significantly up‐regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL‐18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL‐18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV.
Selected commensal‐related bacteria and Toll‐like receptor 3 agonist combinatorial codes synergistically induce interleukin‐12 production by dendritic cells to trigger a T helper type 1 polarizing programme
Authors: Baba Nobuyasu , Samson Sandrine , Bourdet‐Sicard Raphaëlle , Rubio Manuel , Sarfati Marika 
Published: November 2008

SummaryEnteric infections remain a major health problem causing millions of deaths in developing countries. The interplay among the host intestinal epithelium, the mucosa‐associated immune system and microbiota performs an essential role in gut homeostasis and protection against infectious diseases. Dendritic cells (DCs) play a key role in orchestrating protective immunity and tolerance in the gut. The mechanisms by which DCs adapt their responses and discriminate between virulent microbes and trillions of innocuous bacteria remain ill‐defined. Here we investigated the effect of cross‐talk between commensal‐related bacteria (CB) and Toll‐like receptor (TLR) agonists on DC activation and the outcome of the in vitro T helper response. Human monocyte‐derived DCs were exposed to eight different Gram‐positive or Gram‐negative CB strains prior to activation with five different TLR agonists. The key polarizing cytokines interleukin (IL)‐12p70, IL‐10, IL‐1β and IL‐6 were quantified and the fate of naïve T‐cell differentiation was evaluated. We identified a unique combination of Lactobacillus casei and TLR3 signals that acted in synergy to selectively increase IL‐12p70 secretion. Exposure to poly(I:C) converted L. casei‐treated DCs into potent promoters of T helper type 1 (Th1) responses. We propose that DCs can integrate harmless and dangerous non‐self signals delivered by viral products, to mount robust Th1 responses. Thus, in vivo DC targeting with selective probiotics may improve strategies for the management of enteric diseases.
Indicators of pain in neonates at risk for neurological impairment
Authors: Stevens Bonnie , McGrath Patrick , Dupuis Annie , Gibbins Sharyn , Beyene Joseph , Breau Lynn , Camfield Carol , Allen Finley Gordon , Franck Linda S. , Howlett Alexandra , Johnston Celeste , McKeever Patricia , O’Brien Karel , Ohlsson Arne , Yamada Janet 
Published: November 2008

AbstractTitle.  Indicators of pain in neonates at risk for neurological impairment. Aim.  This paper is a report of a study to compare the importance and usefulness ratings of physiological and behavioural indicators of pain in neonates at risk for neurological impairment by nurse clinicians and pain researchers.Background.  Neonates at risk for neurological impairment have not been systematically included in neonatal pain measure development and how clinicians and researchers view pain indicators in these infants is unknown.Methods.  Data triangulation was undertaken in three Canadian Neonatal Intensive Care Units using data from: (a) 149 neonates at high, moderate and low risk for neurological impairment, (b) 95 nurse clinicians from the three units where infant data were collected and (c) 14 international pain researchers. Thirteen indicators were assessed following heel lance in neonates and 39 indicators generated from nurse clinicians and pain researchers were assessed for importance and accuracy. Data were collected between 2004 and 2005.Results.  Across risk groups, indicators with the highest accuracy for discriminating ‘pain’ among neonates were: brow bulge (77–83%), eye squeeze (75–84%), nasolabial furrow (79–81%), and total facial expression (78–83%). Correlations between nurse ratings and neonatal accuracy scores ranged from moderate to none (mild risk r = 0·52, P = 0·07; moderate r = 0·43, P = 0·15; high r = −0·12, P = 0·69). Researchers demonstrated a better understanding of the importance of pain indicators (mild risk, r = 0·91, P < 0·001; moderate 0·85, P < 0·001; 0·0002; high r = 0·64, P = 0·019) than nurse clinicians.Conclusion/Discussion.  Facial actions were rated as the most important indicators of neonatal pain. However, as neurological impairment risk increased, physiological indicators were rated more important by nurse clinicians and pain researchers, opposite to pain indicators demonstrated by neonates.
Modelling late Quaternary changes in plant distribution, vegetation and climate using pollen data from Georgia, Caucasus
Authors: Connor Simon E. , Kvavadze Eliso V. 
Published: November 2008

AbstractAim  To use pollen data, numerical analysis and modelling to reconstruct late Quaternary vegetation and climate in a complex, mountainous environment.Location  Georgia (Caucasus region).Methods  Pollen data were assembled from various sources and used to map: (1) changing frequencies of individual taxa; (2) vegetation changes; and (3) reconstructed climatic parameters for the past 14,000 years. Numerical analyses were performed using two‐way indicator species analysis (twinspan), detrended correspondence analysis (DCA), the modern analogue technique (MAT) and weighted averaging (WA).Results  Mapping of pollen taxa showed that Chenopodiaceae, Artemisia and Ephedra were most abundant in the study area during the late‐glacial. Betula and Corylus expanded during the early Holocene, yielding to Abies, Carpinus, Fagus, Quercus and Castanea. Picea, Pinus, Juglans and Ostrya‐type expanded during the late Holocene. Mixed forests grew in the moist, Black Sea refugium throughout the late Quaternary. Elsewhere in Georgia, the Pleistocene–Holocene transition is recorded as a shift from desert‐steppes to oak‐xerophyte communities and mixed forests. This kind of vegetation remained relatively stable until the mid–late Holocene, when coniferous forests and mountain grasslands advanced. DCA showed that rainfall was most strongly correlated with pollen composition in the study area (r2 = 0.55). No temperature signal was detected. A weighted‐averaging transfer function linking pollen percentages to annual precipitation was selected over a MAT model as it performed better when applied to a validation data set. Rainfall reconstructions indicate widespread aridity at the terminal Pleistocene, followed by a gradual increase in precipitation, peaking during the mid Holocene (7000–4000 cal. yr bp) and generally decreasing thereafter.Main conclusions  On a regional scale, the results confirm those from previous studies of palaeovegetation and palaeoclimate in Western Asia. On a local scale, reconstructions from individual sites often diverge from the regional trend because of edaphic changes, ecological succession, human impacts and other disturbances. Some of these factors are probably responsible for the increasing heterogeneity of Georgia’s vegetation in the latter half of the Holocene.
Microrefugia
Authors: Rull Valentí 
Published: November 2008

AbstractThe concept of microrefugia is widely accepted to explain the post‐glacial colonization of continents, which led to the present‐day biotic configuration of the Earth. However, so far, microrefugia are no more than a ‘theoretical necessity’ without an appropriate biogeographical and ecological characterization. Here, a tentative definition and a classification of microrefugia, based on the existing literature, are proposed for discussion. A deeper biogeographical analysis of the concept is suggested using novel ecological models and methods, in order to develop new hypotheses to be tested with palaeoecological and molecular phylogenetic tools.
Marine, intertidal, freshwater and terrestrial biodiversity of an isolated polar archipelago
Authors: Barnes David K. A. , Kaiser Stefanie , Griffiths Huw J. , Linse Katrin 
Published: November 2008

AbstractAim  We ask how biodiverse is a polar archipelago; how this faunal richness is spread across marine, intertidal, freshwater, terrestrial and parasitic realms; and how fast species are accumulated with increased sampling effort.Location  The South Orkney Islands (SOI), Scotia Arc, Southern Ocean.Methods  We sampled mega‐ and macro‐benthos at the SOI using scuba in the shallows (0–10 m), a rough bottom otter trawl at 150–250 m and an Agassiz trawl and epibenthic sledge, both at depths of 200, 500, 1000 and 1500 m. We also collated species occurrence at the SOI in each realm from a century of literature and modern databases to investigate patterns in species accumulation, endemism, faunistic affinities and bathymetric ranges in three model taxa.Results  Our 11 benthic samples showed that point biodiversity at the SOI is high, yielding 19 classes and 158 species. Nearly a third were new to the area, whilst five species and one genus were new to science. The shallowest samples were richest but had fewest new records of species. Known richness at the SOI is dominated by marine species (1026), of which 821 (83.3%) were benthic. Across all realms, 1224 species (50 classes, 24 phyla) were recorded, of which 43 were intertidal, 64 freshwater, 100 terrestrial, 60 parasitic and 40 birds. Species accumulation curves for model taxa showed new sampling yields about 0.75% per sample of known benthic richness, so by Antarctic standards we know the SOI quite well. Most species are Southern Ocean endemics, but very few occur only at the SOI.Main conclusions  This first estimate of faunal biodiversity of a polar locality demonstrates both high richness and high levels of knowledge at the SOI. As suspected but never quantified, the benthos dominates polar biodiversity, at least at the SOI. Marine species there constitute 20% of those recently listed for the entire Southern Ocean, whilst > 60% of terrestrial species are known from Antarctica. The SOI, being one of the better‐studied polar locations, of known age and with a discrete shelf, represent an important source of comparison for biodiversity studies. Our data clearly show that richness and our knowledge of the polar fauna differ across environments.
Phylogeography: retrospect and prospect
Authors: Avise John C. 
Published: November 2008

AbstractPhylogeography has grown explosively in the two decades since the word was coined and the discipline was outlined in 1987. Here I summarize the many achievements and novel perspectives that phylogeography has brought to population genetics, phylogenetic biology and biogeography. I also address future directions for the field. From the introduction of mitochondrial DNA assays in the late 1970s, to the key distinction between gene trees and species phylogenies, to the ongoing era of multi‐locus coalescent theory, phylogeographic perspectives have consistently challenged conventional genetic and evolutionary paradigms, and they have forged empirical and conceptual bridges between the formerly separate disciplines of population genetics (microevolutionary analysis) and phylogenetic biology (in macroevolution).
Local–regional diversity relationship varies with spatial scale in lotic diatoms
Authors: Soininen Janne , Heino Jani , Kokocinski Mikolaj , Muotka Timo 
Published: November 2008

AbstractAim  Ecologists have shown increasing interest in the relative roles of local and regional factors in structuring biotic communities. One approach to studying this is to examine the relationship between local species richness (LSR) and regional species richness (RSR). We examined the LSR–RSR relationship in stream diatoms, using two data sets that varied in spatial extent. At broad spatial extent ranging across drainage systems, we expected climatic and dispersal‐related factors to constrain LSR, thus resulting in a linear LSR–RSR relationship. However, at small spatial scales dispersal across sites should be unconstrained, resulting in strong local interactions and a weak or asymptotic LSR–RSR relationship.Location  Boreal streams in Finland.Methods  For data set 1, we sampled 15 stream riffles (localities) in each of eight drainage systems (regions), with the latitudinal gradient between the southernmost and northernmost sites being almost 1100 km. For data set 2, a locality for estimating LSR was a single stone, and each riffle represented a region for estimating RSR. We sampled 20 stones in each of eight riffles. We used linear regressions to examine the relationship between LSR and RSR across regions. We used both observed richness values, as well as values estimated with the Chao1 estimator.Results  We found a relatively strong linear relationship between the Chao1‐estimated mean LSR and RSR (R2 = 0.654, P = 0.015) across drainage systems. The slope of the regression was 0.643 and it did not differ from 1.0, thus indicating linearity. At the riffle scale, however, LSR and RSR were not linearly related, and the slope of the regression (0.039) differed significantly from 1.0, indicating curvilinearity.Main conclusions  These results suggest that the relationship between mean LSR and RSR varies across spatial scales in diatoms – from significantly linear at large scales to curvilinear at small scales. These plots imply strong regional enrichment in stream diatoms across drainage systems. Their diversity is thus determined largely by the composition of the regional species pool, as also in many macroorganisms. In contrast, at small spatial scales the LSR–RSR relationship implied a hard limit to local diversity, reflecting the primacy of local processes.
A matter of life and death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction pathway
Authors: Dubrac Sarah , Bisicchia Paola , Devine Kevin M. , Msadek Tarek 
Published: November 2008

SummaryThe WalK/WalR (aka YycG/YycF) two‐component system (TCS), originally identified in Bacillus subtilis, is very highly conserved and specific to low G+C Gram‐positive bacteria, including a number of important pathogens. An unusual feature is that this system is essential for viability in most of these bacteria. Recent studies have revealed conserved functions for this system, defining this signal transduction pathway as a crucial regulatory system for cell wall metabolism, that we have accordingly renamed WalK/WalR. Here we review the cellular role of the WalK/WalR TCS in different bacterial species, focusing on the function of genes in its regulon, as well as variations in walRK operon structure and the composition of its regulon. We also discuss the nature of its essentiality and the potential type of signal being sensed. The WalK histidine kinase of B. subtilis has been shown to localize to the divisome and we suggest that the WalKR system acts as an information conduit between extracytoplasmic cellular structures and intracellular processes required for their synthesis, playing a vital role in effectively co‐ordinating peptidoglycan plasticity with the cell division process.
The Pta–AckA pathway controlling acetyl phosphate levels and the phosphorylation state of the DegU orphan response regulator both play a role in regulating Listeria monocytogenes motility and chemotaxis
Authors: Gueriri Ibtissem , Bay Sylvie , Dubrac Sarah , Cyncynatus Camille , Msadek Tarek 
Published: November 2008

SummaryDegU is considered to be an orphan response regulator in Listeria monocytogenes since the gene encoding the cognate histidine kinase DegS is absent from the genome. We have previously shown that DegU is involved in motility, chemotaxis and biofilm formation and contributes to L. monocytogenes virulence. Here, we have investigated the role of DegU phosphorylation in Listeria and shown that DegS of Bacillus subtilis can phosphorylate DegU of L. monocytogenes in vitro. We introduced the B. subtilis degS gene into L. monocytogenes, and showed that this leads to highly increased expression of motility and chemotaxis genes, in a DegU‐dependent fashion. We inactivated the predicted phosphorylation site of DegU by replacing aspartate residue 55 with asparagine and showed that this modified protein (DegUD55N) is no longer phosphorylated by DegS in vitro. We show that although the unphosphorylated form of DegU retains much of its activity in vivo, expression of motility and chemotaxis genes is lowered in the degUD55N mutant. We also show that the small‐molecular‐weight metabolite acetyl phosphate is an efficient phosphodonor for DegU in vitro and our evidence suggests this is also true in vivo. Indeed, a L. monocytogenesΔptaΔackA mutant that can no longer synthesize acetyl phosphate was found to be strongly affected in chemotaxis and motility gene expression and biofilm formation. Our findings suggest that phosphorylation by acetyl phosphate could play an important role in modulating DegU activity in vivo, linking its phosphorylation state to the metabolic status of L.  monocytogenes.
Spa32 interaction with the inner‐membrane Spa40 component of the type III secretion system of Shigella flexneri is required for the control of the needle length by a molecular tape measure mechanism
Authors: Botteaux Anne , Sani Musa , Kayath Christian A. , Boekema Egbert J. , Allaoui Abdelmounaaïm 
Published: November 2008

SummaryThe effectors of enterocyte invasion by Shigella are dependent on a type III secretion system that contains a needle whose length average does not exceed 50 nm. Previously, we reported that Spa32 is required for needle length control as well as to switch substrate specificity from MxiH to Ipa proteins secretion. To identify functional domains of Spa32, 11 truncated variants were constructed and analysed for their capacity (i) to control the needle's length; (ii) to secrete the Ipa proteins; and (iii) to invade HeLa cells. Deletion at either the N‐terminus or C‐terminus affect Spa32 function in all cases, but Spa32 variants lacking internal residues 37–94 or 130–159 retained full Spa32 function. Similarly, a Spa32 variant obtained by inserting of the YscP's ruler domain retained Spa32 function although it programmed slightly elongated needles. Using the GST pull‐down assay, we show that residues 206–246 are required for Spa32 binding to the C‐terminus of Spa40, an inner membrane protein required for Ipa proteins secretion. Our data clearly demonstrate that shortening Spa32 affects the length of the needle in a comparable manner to the spa32 mutant, indicating that the control of needle length does not require a molecular ruler mechanism.