bluuebunny/crossref_metadata_2025 huggingface dataset:
Avian evolution: from Darwin's finches to a new way of thinking about avian forebrain organization and behavioural capabilities
Authors: Reiner Anton
Published: October 2008

The study of birds, especially the Galapagos finches, was important to Darwin in the development of the theory of evolution by natural selection. Birds have also been at the centre of a recent reformulation in understanding cerebral evolution and the substrates for higher cognition. While it was once thought that birds possess a simple cerebrum and were thus limited to instinctive behaviours, it is now clear that birds possess a well-developed cerebrum that looks very different from the mammalian cerebrum but can support a cognitive ability that for some avian species rivals that in primates.
Autotomy reduces immune function and antioxidant defence
Authors: Slos Stefanie , De Block Marjan , Stoks Robby
Published: October 2008

Costs of autotomy, an antipredator defence, are typically explained by impaired mobility; yet physiologically mediated costs may also play a role. Given the resemblance to wounding, a decreased immune function and an associated reduction in antioxidant defence is expected after autotomy. In line with this, after lamellae autotomy, larvae of the damselfly
Lestes viridis
showed lower levels of innate immunity (i.e. phenoloxidase, PO) and antioxidant defence (superoxide dismutase, SOD). Levels of catalase (CAT) remained, however, unaffected. In line with its cytotoxicity, PO covaried positively with CAT, yet negatively with SOD. We identified a novel cost of autotomy in terms of a reduced innate immunity, which may provide an alternative explanation for the often observed costs of autotomy and which may generate indirect interactions between predators and parasites.
An interrupted story: French translations from
Philosophical Transactions
in the seventeenth and eighteenth centuries
Authors: Turner Anthony
Published: October 2008

Although consistently recognized as desirable by both the Royal Society and the Académie des Sciences, translations of
Philosophical Transactions of the Royal Society
were only infrequently undertaken officially. More successful were some private attempts, which by the end of the eighteenth century had produced a virtually complete translation, albeit only of Lowthorp's abridgements.
Frequency locking in an injection-locked frequency divider equation
Authors: Bartuccelli Michele V , Deane Jonathan H.B , Gentile Guido
Published: October 2008

We consider a model for a resonant injection-locked frequency divider, and study analytically the locking onto rational multiples of the driving frequency. We provide explicit formulae for the width of the plateaux appearing in the devil's staircase structure of the lockings, and in particular show that the largest plateaux correspond to even integer values for the ratio of the frequency of the driving signal to the frequency of the output signal. Our results prove the experimental and numerical results available in the literature.
Chemical disguise as particular caste of host ants in the ant inquiline parasite
Niphanda fusca
(Lepidoptera: Lycaenidae)
Authors: Hojo Masaru K , Wada-Katsumata Ayako , Akino Toshiharu , Yamaguchi Susumu , Ozaki Mamiko , Yamaoka Ryohei
Published: October 2008

The exploitation of parental care is common in avian and insect ‘cuckoos’ and these species engage in a coevolutionary arms race. Caterpillars of the lycaenid butterfly
Niphanda fusca
develop as parasites inside the nests of host ants (
Camponotus japonicus
) where they grow by feeding on the worker trophallaxis. We hypothesized that
N. fusca
caterpillars chemically mimic host larvae, or some particular castes of the host ant, so that the caterpillars are accepted and cared for by the host workers. Behaviourally, it was observed that the host workers enthusiastically tended glass dummies coated with the cuticular chemicals of larvae or males and those of
N. fusca
caterpillars living together. Cuticular chemical analyses revealed that
N. fusca
caterpillars grown in a host ant nest acquired a colony-specific blend of cuticular hydrocarbons (CHCs). Furthermore, the CHC profiles of the
N. fusca
caterpillars were particularly close to those of the males rather than those of the host larvae and the others. We suggest that
N. fusca
caterpillars exploit worker care by matching their cuticular profile to that of the host males, since the males are fed by trophallaxis with workers in their natal nests for approximately ten months.
Experimental evolution of a sexually selected display in yeast
Authors: Rogers David W , Greig Duncan
Published: October 2008

The fundamental principle underlying sexual selection theory is that an allele conferring an advantage in the competition for mates will spread through a population. Remarkably, this has never been demonstrated empirically. We have developed an experimental system using yeast for testing genetic models of sexual selection. Yeast signal to potential partners by producing an attractive pheromone; stronger signallers are preferred as mates. We tested the effect of high and low levels of sexual selection on the evolution of a gene determining the strength of this signal. Under high sexual selection, an allele encoding a stronger signal was able to invade a population of weak signallers, and we observed a corresponding increase in the amount of pheromone produced. By contrast, the strong signalling allele failed to invade under low sexual selection. Our results demonstrate, for the first time, the spread of a sexually selected allele through a population, confirming the central assumption of sexual selection theory. Our yeast system is a powerful tool for investigating the genetics of sexual selection.
Indirect genetic effects and the evolution of aggression in a vertebrate system
Authors: Wilson Alastair J , Gelin Uriel , Perron Marie-Claude , Réale Denis
Published: October 2008

Aggressive behaviours are necessarily expressed in a social context, such that individuals may be influenced by the phenotypes, and potentially the genotypes, of their social partners. Consequently, it has been hypothesized that indirect genetic effects (IGEs) arising from the social environment will provide a major source of heritable variation on which selection can act. However, there has been little empirical scrutiny of this to date. Here we test this hypothesis in an experimental population of deer mice (Peromyscus maniculatus). Using quantitative genetic models of five aggression traits, we find repeatable and heritable differences in agonistic behaviours of focal individuals when presented with an opponent mouse. For three of the traits, there is also support for the presence of IGEs, and estimated correlations between direct and indirect genetic (rAO,F) effects were high. As a consequence, any selection for aggression in the focal individuals should cause evolution of the social environment as a correlated response. In two traits, strong positiverAO,Fwill cause the rapid evolution of aggression, while in a third case changes in the phenotypic mean will be constrained by negative covariance between direct and IGEs. Our results illustrate how classical analyses may miss important components of heritable variation, and show that a full understanding of evolutionary dynamics requires explicit consideration of the genetic component of the social environment.
A thin-shelled reptile from the Late Triassic of North America and the origin of the turtle shell
Authors: Joyce Walter G , Lucas Spencer G , Scheyer Torsten M , Heckert Andrew B , Hunt Adrian P
Published: October 2008

A new, thin-shelled fossil from the Upper Triassic (Revueltian: Norian) Chinle Group of New Mexico,
Chinlechelys tenertesta
, is one of the most primitive known unambiguous members of the turtle stem lineage. The thin-shelled nature of the new turtle combined with its likely terrestrial habitat preference hint at taphonomic filters that basal turtles had to overcome before entering the fossil record.
Chinlechelys tenertesta
possesses neck spines formed by multiple osteoderms, indicating that the earliest known turtles were covered with rows of dermal armour. More importantly, the primitive, vertically oriented dorsal ribs of the new turtle are only poorly associated with the overlying costal bones, indicating that these two structures are independent ossifications in basal turtles. These novel observations lend support to the hypothesis that the turtle shell was originally a complex composite in which dermal armour fused with the endoskeletal ribs and vertebrae of an ancestral lineage instead of forming de novo. The critical shell elements (i.e. costals and neurals) are thus not simple outgrowths of the bone of the endoskeletal elements as has been hypothesized from some embryological observations.
Atlantic salmon eggs favour sperm in competition that have similar major histocompatibility alleles
Authors: Yeates Sarah E , Einum Sigurd , Fleming Ian A , Megens Hendrik-Jan , Stet René J.M , Hindar Kjetil , Holt William V , Van Look Katrien J.W , Gage Matthew J.G
Published: October 2008

Polyandry and post-copulatory sexual selection provide opportunities for the evolution of female differential sperm selection. Here, we examined the influence of variation in major histocompatibility (MH) class I allelic composition upon sperm competition dynamics in Atlantic salmon. We ran
in vitro
fertilization competitions that mimicked the gametic microenvironment, and replicated a paired-male experimental design that allowed us to compare differences in sperm competition success among males when their sperm compete for eggs from females that were genetically either similar or dissimilar at the MH class I locus. Concurrently, we measured variation in spermatozoal traits that are known to influence relative fertilization success under these conditions. Contrary to the findings demonstrating mechanisms that promote MH complex heterozygosity, our results showed that males won significantly greater relative fertilization success when competing for eggs from genetically similar females at the MH class I. This result also showed covariation with the known influences of sperm velocity on relative fertilization success. We discuss these unexpected findings in relation to sperm–egg recognition and hybridization avoidance mechanisms based upon immunogenetic variation.
The past is a guide to the future? Comparing Middle Pliocene vegetation with predicted biome distributions for the twenty-first century
Authors: Salzmann U , Haywood A.M , Lunt D.J
Published: October 2008

During the Middle Pliocene, the Earth experienced greater global warmth compared with today, coupled with higher atmospheric CO
2
concentrations. To determine the extent to which the Middle Pliocene can be used as a ‘test bed’ for future warming, we compare data and model-based Middle Pliocene vegetation with simulated global biome distributions for the mid- and late twenty-first century. The best agreement is found when a Middle Pliocene biome reconstruction is compared with a future scenario using 560 ppmv atmospheric CO
2
. In accordance with palaeobotanical data, all model simulations indicate a generally warmer and wetter climate, resulting in a northward shift of the taiga–tundra boundary and a spread of tropical savannahs and woodland in Africa and Australia at the expense of deserts. Our data–model comparison reveals differences in the distribution of polar vegetation, which indicate that the high latitudes during the Middle Pliocene were still warmer than its predicted modern analogue by several degrees. However, our future scenarios do not consider multipliers associated with ‘long-term’ climate sensitivity. Changes in global temperature, and thus biome distributions, at higher atmospheric CO
2
levels will not have reached an equilibrium state (as is the case for the Middle Pliocene) by the end of this century.
LAB-1 antagonizes the Aurora B kinase in C. elegans
Authors: de Carvalho Carlos Egydio , Zaaijer Sophie , Smolikov Sarit , Gu Yanjie , Schumacher Jill M. , Colaiácovo Monica P.
Published: October 2008

The Shugoshin/Aurora circuitry that controls the timely release of cohesins from sister chromatids in meiosis and mitosis is widely conserved among eukaryotes, although little is known about its function in organisms whose chromosomes lack a localized centromere. Here we show that Caenorhabditis elegans chromosomes rely on an alternative mechanism to protect meiotic cohesin that is shugoshin-independent and instead involves the activity of a new chromosome-associated protein named LAB-1 (Long Arm of the Bivalent). LAB-1 preserves meiotic sister chromatid cohesion by restricting the localization of the C. elegans Aurora B kinase, AIR-2, to the interface between homologs via the activity of the PP1/Glc7 phosphatase GSP-2. The localization of LAB-1 to chromosomes of dividing embryos and the suppression of mitotic-specific defects in air-2 mutant embryos with reduced LAB-1 activity support a global role of LAB-1 in antagonizing AIR-2 in both meiosis and mitosis. Although the localization of a GFP fusion and the analysis of mutants and RNAi-mediated knockdowns downplay a role for the C. elegans shugoshin protein in cohesin protection, shugoshin nevertheless helps to ensure the high fidelity of chromosome segregation at metaphase I. We propose that, in C. elegans, a LAB-1-mediated mechanism evolved to offset the challenges of providing protection against separase activity throughout a larger chromosome area.
More complexity to the Bloom’s syndrome complex
Authors: Liu Yilun , West Stephen C.
Published: October 2008

Bloom’s syndrome is caused by mutations in the BLM gene. The BLM gene product, BLM helicase, forms a complex with two other proteins, DNA topoisomerase IIIα and RMI1. In this issue of Genes & Development, Wang and colleagues (2843–2855) and Meetei and colleagues (2856–2868) report the discovery of a fourth component of this complex called RMI2. RMI2 may be a representative of a new family of OB-fold-containing proteins that are important for complex stabilization and checkpoint response.
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing
Authors: Lagarou Anna , Mohd-Sarip Adone , Moshkin Yuri M. , Chalkley Gillian E. , Bezstarosti Karel , Demmers Jeroen A.A. , Verrijzer C. Peter
Published: October 2008

Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
The Arabidopsis COP9 Signalosome Subunit 7 Is a Model PCI Domain Protein with Subdomains Involved in COP9 Signalosome Assembly
Authors: Dessau Moshe , Halimi Yair , Erez Tamir , Chomsky-Hecht Orna , Chamovitz Daniel A. , Hirsch Joel A.
Published: October 2008

The COP9 Signalosome (CSN) is a multiprotein complex that was originally identified in Arabidopsis thaliana as a negative regulator of photomorphogenesis and subsequently shown to be a general eukaryotic regulator of developmental signaling. The CSN plays various roles, but it has been most often implicated in regulating protein degradation pathways. Six of eight CSN subunits bear a sequence motif called PCI. Here, we report studies of subunit 7 (CSN7) from Arabidopsis, which contains such a motif. Our in vitro and structural results, based on 1.5 Å crystallographic data, enable a definition of a PCI domain, built from helical bundle and winged helix subdomains. Using functional binding assays, we demonstrate that the PCI domain (residues 1 to 169) interacts with two other PCI proteins, CSN8 and CSN1. CSN7 interactions with CSN8 use both PCI subdomains. Furthermore, we show that a C-terminal tail outside of this PCI domain is responsible for association with the non-PCI subunit, CSN6. In vivo studies of transgenic plants revealed that the overexpressed CSN7 PCI domain does not assemble into the CSN, nor can it complement a null mutation of CSN7. However, a CSN7 clone that contains the PCI domain plus part of the CSN6 binding domain can complement the null mutation in terms of seedling viability and photomorphogenesis. These transgenic plants, though, are defective in adult growth, suggesting that the CSN7 C-terminal tail plays additional functional roles. Together, the findings have implications for CSN assembly and function, highlighting necessary interactions between subunits.
The effects of melatonin on sleep–wake rhythm of daytime haemodialysis patients: a randomized, placebo‐controlled, cross‐over study (EMSCAP study)
Authors: Koch Birgit C. P. , Nagtegaal J. Elsbeth , Hagen E. Chris , Van Der Westerlaken Monique M. L. , Boringa Jan B. S. , Kerkhof Gerard A. , Ter Wee Piet M.
Published: October 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Disturbances of sleep–wake rhythm are frequently reported in daytime haemodialysis patients.

• The melatonin rhythm, which plays an important role in synchronization of the sleep–wake rhythm, is disturbed in this patient group.

• In other patient groups with disturbed melatonin rhythm, use of exogenous melatonin resulted in an improvement of sleep quality and melatonin rhythm.

WHAT THIS STUDY ADDS

• This is the first study on the effects of exogenous melatonin on sleep–wake rhythm in haemodialysis patients.

• Due to exogenous melatonin, sleep parameters such as sleep fragmentation, sleep onset latency and subjective sleep quality improved.

• Nocturnal melatonin rise was recovered.

AIM

The aim of this study was to investigate the effects of exogenous melatonin on sleep–wake rhythm in haemodialysis patients.

METHODS

The study design is a randomized, double‐blind, placebo‐controlled, cross‐over study of 3 × 6 weeks melatonin 3 mg at 22.00 h every night. Haemodialysis patients were asked to fill out a sleep questionnaire and to wear an actometer to record their sleep problems objectively. Furthermore, melatonin concentrations in saliva were sampled the night after daytime haemodialysis and the consecutive night. Actometers, the sleep questionnaire and melatonin concentrations were repeated during the study.

RESULTS

In total, 20 patients (six female, median age 71 years) completed the investigation. On nights after daytime dialysis, objective sleep onset latency decreased significantly from a median of 44.5 (placebo) to a median of 15.5 min with melatonin (P < 0.01). Sleep efficiency increased from 67.3 to 73.1% with melatonin (P < 0.05). Actual sleep time increased from 376 min (placebo) to 388 min with melatonin (P < 0.01), and sleep fragmentation decreased from 4.5 to 3.1 (P < 0.01). Furthermore, subjective sleep parameters improved also. Patients reported less time needed to fall asleep (P < 0.05) and fewer wake periods (P < 0.05) on the nights with and without daytime dialysis and an increase in sleep time on the night of daytime dialysis (P < 0.05). Furthermore, the nocturnal melatonin rise was recovered.

CONCLUSION

Treatment with melatonin resulted in an improvement of subjective and objective sleep parameters, as well as a recovered nocturnal melatonin rhythm.
Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study
Authors: Rakic Ignjatovic Anita , Miljkovic Branislava , Todorovic Dejan , Timotijevic Ivana , Pokrajac Milena
Published: October 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs.

• Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad‐spectrum inhibitor, and CBZ as a potent inducer of a variety of drug‐metabolizing enzymes.

• There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders.

WHAT THIS STUDY ADDS

• VPA does not significantly affect PK or metabolism of MCB at steady state.

• CBZ significantly decreases MCB exposure. This effect is time‐dependent, being more pronounced after 3–5 weeks of co‐administration.

AIM

To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients.

METHODS

Twenty‐one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady‐state plasma PK parameters of MCB and its two metabolites, Ro 12‐8095 and Ro 12‐5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales.

RESULTS

CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l−1; 95% confidence interval (CI) −4.84863, −0.66194; P = 0.01] and Cmax by 28% (from 1.911 to 1.383 mg l−1; 95% CI −0.98197, −0.07518; P < 0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h−1 kg−1; 95% CI 0.00086, 0.26171; P < 0.05) after 4 weeks of co‐administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l−1; 95% CI −0.77479, −0.03301; P < 0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good.

CONCLUSIONS

VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time‐dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB–CBZ PK interaction needs to be further evaluated in a more comprehensive study.
The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patients
Authors: Montes Ramón , Nantes Óscar , Alonso Álvaro , Zozaya José M. , Hermida José
Published: October 2008

The VKORC1 c.−1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty‐nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4·19 (1·59–11·04)]; amiodarone use [adjusted OR (95% CI) = 9·97 (1·75–56·89)]; or aspirin use [adjusted OR (95% CI) = 8·97 (1·66–48·34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0·50 (0·26–0·99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.
Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells
Authors: Nielsen C H , Albertsen L , Bendtzen K , Baslund B
Published: October 2008

The mechanism of action of methotrexate (MTX) in autoimmune diseases (AID) is unclear. A pro-apoptotic effect has been demonstrated in mitogen-stimulated peripheral blood mononuclear cells (PBMC), but studies employing conventional antigens have disputed a pro-apoptotic effect. CD4+ T helper (Th) cells play a significant role in most AID. We therefore examined directly, by flow cytometry, the uptake of MTX by the T helper (Th) cells stimulated for 6 days with Candida albicans (CA) or tetanus toxoid (TT), and its consequences with respect to induction of apoptosis. While none of the resting Th cells took up MTX, nearly all the dividing Th cells did, and this abrogated further cell division. Among dividing Th cells, MTX induced an approximately sixfold increase over baseline levels in the proportion of apoptotic cells. This proportion could be reverted to baseline by the addition of folic acid. Exposure of CA-stimulated PBMC to MTX significantly increased their level of cleaved poly(ADP-ribose) polymerase (PARP), and a similar tendency was observed in TT-stimulated cells. Unlike CA and TT, the mitogen phytohaemagglutinin (PHA) induced proliferation of both CD4– and CD4+ T cells, and induced apoptosis in both undivided and divided Th cells. PHA-induced apoptosis involved activation of caspase-3 and the anti-apoptotic protein Bcl-2 in addition to PARP cleavage, suggesting that PHA induces apoptosis via different pathways than CA and TT. We suggest that the latter are more representative of stimulation with self-antigens in AID, and that a pro-apoptotic effect of MTX on self-antigen-stimulated Th cells contributes to the effect of MTX in the treatment of AID.
Clinical significance of autoantibodies recognizing Sjögren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjögren's syndrome
Authors: Goëb V , Salle V , Duhaut P , Jouen F , Smail A , Ducroix J-P , Tron F , Le Loët X , Vittecoq O
Published: October 2008

The aim of our study was (i) to compare the clinical and biological characteristics of 148 (137 women, 11 men) primary Sjögren's syndrome (pSS) patients at diagnosis as a function of their sex and (ii) to assess the prognostic value of anti-calpastatin and anti-alpha-fodrin autoantibodies. In addition, the presence of anti-nuclear antibodies (ANA), anti-52- and 60-kDa Sjögren's syndrome A (SSA), anti-Sjögren's syndrome B (SSB), anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factors (RF) of IgA, IgG and IgM isotypes was sought in sera collected at pSS onset. Raynaud's syndrome, significantly more frequent in women, was the only systemic manifestation of pSS whose frequency differed significantly as a function of the patient's sex (P = 0·02). ANA (P = 0·001) and anti-60-kDa SSA autoantibodies (P = 0·03) were significantly more common in women, while men never synthesized detectable levels of anti-SSB, anti-calpastatin or IgG anti-alpha-fodrin autoantibodies. In addition, anti-CCP autoantibodies were found in low percentages of pSS patients (4% F/18% M). The absence of autoantibodies does not exclude the diagnosis of pSS in men that will be based mainly on the anatomopathological findings of a minor salivary gland biopsy. Positivity of anti-60-kDa SSA, anti-SSB, anti-calpastatin, IgA and IgG anti-alpha-fodrin antibodies is not associated with pSS clinical and biological severity.
The loss of immunodominant epitopes affects interferon-γ production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte responsein vitro
Authors: Berkhoff E G M , Geelhoed-Mieras M M , Verschuren E J , van Baalen C A , Gruters R A , Fouchier R A M , Osterhaus A D M E , Rimmelzwaan G F
Published: October 2008

In the present study, we examined the effect of the loss of the human leucocyte antigen (HLA)-B*3501-restricted nucleoprotein (NP)418–426 epitope on interferon (IFN)-γ-production and lytic activity of the human cytotoxic T lymphocyte (CTL) response in vitro. Extensive amino acid variation at T cell receptor contact residues of the NP418–426 epitope has led to repeated evasion from specific CTL. We generated recombinant influenza viruses with variants of the NP418–426 epitope, which were used to stimulate peripheral blood mononuclear cells obtained from six HLA-B*3501-positive study subjects in order to expand virus-specific CTL. Loss of the NP418–426 epitope resulted in a significant reduction of IFN-γ-expressing CD8+ T cells, similar to that observed previously after the loss of the HLA-B*2705-restricted NP383–391 epitope. In addition, the effect of the loss of the NP418–426 epitope on the lytic activity of the virus-specific CTL response was assessed. Also this functional property of the virus-specific CTL response was affected significantly by the loss of this and the NP383–391 epitope, as determined using the newly developed fluorescent antigen-transfected target cell (FATT)–CTL assay. These findings indicate that the loss of single immunodominant epitopes affects the functionality of the virus-specific CTL response significantly.
The chemokine network. I. How the genomic organization of chemokines contains clues for deciphering their functional complexity
Authors: Colobran R , Pujol-Borrell R , Armengol Ma P , Juan M
Published: October 2008

Chemokines are a superfamily of small structurally related cytokines that have evolved to form a complex network of proteins that typically regulate leucocyte traffic but also carry very diverse sets of immune and non-immune functions. Two general features of cytokines, redundancy and promiscuity, are particularly prominent in chemokines. In part, these properties result from repeated processes of gene duplication and diversification, which has led to the present complex genomic map of chemokines, which contains cases of non-allelic isoforms, copy number polymorphisms and classical allelic variation. This genomic complexity is compounded with pre-translational and post-translational mechanisms resulting in a complex network of proteins whose essential functions are maintained, constituting a remarkable case of robustness reminiscent of crucial metabolic pathways. This reflects the adaptation of a system under strong evolutive pressure, supporting the concept that the chemokine system is essential for the coordination, regulation and fine-tuning of the type of immune response. In this first review, we analyse currently available data on the chemokine superfamily, focusing on its complex genomic organization. Genes encoding essential inflammatory chemokines are grouped into defined chromosomal locations as clusters and miniclusters that, from the genetic point of view, can be considered single entities given their overall functions (many ligands of a cluster bind to a few shared receptors). We will try to interpret this genomic organization of chemokines in relation to the main functions acquired by each individual member or by each cluster. In a second review, we shall focus on the relationship of chemokine variability and disease susceptibility.
Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin-10 gene-deficient mice with colitis
Authors: Matsuda C , Ito T , Song J , Mizushima T , Tamagawa H , Kai Y , Hamanaka Y , Inoue M , Nishida T , Matsuda H , Sawa Y
Published: October 2008

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10–/–) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10–/– mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10–/– mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN-γ production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10–/– mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN-γ production.
Mannan-binding lectin may facilitate the clearance of circulating immune complexes − implications from a study on C2-deficient individuals
Authors: Saevarsdottir S , Steinsson K , Ludviksson B R , Grondal G , Valdimarsson H
Published: October 2008

Deficiency of both mannan-binding lectin (MBL) and complement components C4 and C2 has been associated with increased risk of systemic lupus erythematosus (SLE). MBL can activate the complement system either through C4 and C2 or directly through C3. Circulating immune complexes (CICs) are believed to play a pathogenic role in SLE and MBL has been shown to bind certain forms of immunoglobulins, including IgM, IgG and IgA. Thus, MBL might promote CIC clearance. In order to evaluate this, six individuals with non-functional classical pathway due to the rare homozygous C2 deficiency were chosen, as the classical pathway is known to have a fundamental role in CIC clearance. Four of the six C2-deficient individuals had SLE, two of whom also had MBL deficiency. MBL serum levels and genotypes were compared with the serum levels of CICs, as measured by their content of kappa, lambda, IgM, IgA, IgG and C3 opsonization. The C2-deficient individuals had higher serum levels of CICs than 16 healthy controls (P < 0·0001). Furthermore, an inverse association was observed between MBL and CIC levels in the C2-deficient individuals, which was strongest for IgM-CICs (r = − 0·84, P = 0·037). Moreover, C3 opsonization of the CICs correlated positively with MBL levels in the C2-deficient individuals (r = 0·89, P = 0·017). In conclusion, individuals with C2 deficiency have increased levels of CICs and MBL may facilitate their clearance. Defective CIC clearance might partly explain the increased risk of SLE associated with low MBL.
Lymphocyte–hepatic stellate cell proximity suggests a direct interaction
Authors: Muhanna N , Horani A , Doron S , Safadi R
Published: October 2008

Recent functional research studies suggest an anti-fibrotic role for natural killer (NK) cells coupled with a profibrotic role for CD8 cells. However, the morphological cellular interplay between the different cell types is less clear. To investigate lymphocyte/hepatic stellate cell (HSC) interactions, hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) intraperitoneally (i.p.) for 4 weeks in C57Bl/6 mice. Animals were killed at 0, 1, 2, 3 and 4 weeks. Liver sections were stained for Sirius red. Confocal microscopy was used to evaluate alpha smooth-muscle actin (αSMA) and lymphocyte subsets in liver sections. At weeks 0 and 4, liver protein extracts were assessed for αSMA by Western blotting and isolated liver lymphocytes as well as HSC were analysed by fluorescence activated cell sorter (FACS). Similar to the results obtained from classical Sirius red staining and αSMA blotting, analysis of liver sections by confocal microscopy revealed a marked and continuous accumulation of αSMA staining along sequential experimental check-points after administering CCl4. Although the number of all liver lymphocyte subsets increased following fibrosis induction, FACS analysis revealed an increase in the distribution of liver CD8 subsets and a decrease of CD4 T cells. Confocal microscopy showed a significant early appearance of CD8 and NK cells, and to a lesser extent CD4 T cells, appearing only from week 2. Lymphocytes were seen in proximity only to HSC, mainly in the periportal area and along fibrotic septa, suggesting a direct interaction. Notably, lymphocyte subsets were undetectable in naive liver sections. Freshly isolated HCS show high expression of major histocompatibility complex (MHC) class II and CD11c. In the animal model of hepatic fibrosis, lymphocytes infiltrate into the liver parenchyma and it is thought that they attach directly to activated HSC. Because HSCs express CD11c/class II molecules, interactions involving them might reflect that HSCs have an antigen-presenting capacity.
Expected future plague levels in a wildlife host under different scenarios of climate change
Authors: SNÄLL T. , BENESTAD R. E. , STENSETH N. C.
Published: October 2008

We predicted future plague and black‐tailed prairie dog dynamics in the North American prairies under different scenarios of climate change. A climate‐driven model for the joint dynamic of the host–parasite system was used. Projections for the regional climate were obtained through empirical–statistical downscaling of global climate scenarios generated by an ensemble of global climate models for the recent Fourth Assessment Report by the IPCC. The study shows the uncertainties involved in predicting future regional climate and climate‐driven population dynamics, but reveals that unchanged or lower levels of plague, leading to increased black‐tailed prairie dog colonies, can be expected. Less plague is particularly expected for scenarios that assume the highest emission of greenhouse gases associated with the greatest projected future warming. Moreover, under high‐emission scenarios, decreased probabilities of extremely high numbers of infected colonies are expected, along with decreased probabilities of extremely low total numbers of colonies. The assumed main underlying mechanism is an inhibiting effect of high temperatures on fleas (dispersal vector) and on flea‐mediated transmission of the disease‐causing bacterium. Our study highlights the importance of using dynamic ecological (here host–parasite) models together with ensembles of climate projections to investigate the responses of populations and parasites to a changed climate.
Mediterranean forest dynamics and forest bird distribution changes in the late 20th century
Authors: GIL‐TENA ASSU , BROTONS LLUÍS , SAURA SANTIAGO
Published: October 2008

Processes derived from global change such as land‐use changes, climate warming or modifications in the perturbation regime may have opposite effects on forest extent and structure with still unknown consequences on forest biodiversity at large spatial scales. In the present study, we aimed at determining forest dynamics associated with global change processes (forest spread, maturation and fire) that have driven the variation in forest bird distributions in Mediterranean forest ecosystems in recent years. The study was located in Catalonia (NE Spain) and used changes in richness of specialist and generalist forest bird species in the last 20 years of the 20th century as indicators of forest biodiversity change. Forest bird distribution changes showed strong spatial patterns and appeared to be related to population processes occurring beyond sampling units (10 km × 10 km squares). Forest maturation appeared as the most important driver of such changes because most of the studied species have a non‐Mediterranean origin and are associated with more mature forests. To a lower degree, forest spread also contributed to forest bird distribution changes whereas the impact of forest fires was not associated to a decrease in the richness of either group of forest species. Given the relatively coarse scale at which our study was conducted, caution should be taken when extrapolating our results to the possible future impacts of climate change on fire regime and forest bird distribution. Our results indicate that large‐scale forest maturation and spread due mainly to land abandonment in Catalonia has overridden the potentially negative effects of fires on forest bird distributions and are currently driving changes in forest biodiversity patterns across the region.
Variation in abundance across a species' range predicts climate change responses in the range interior will exceed those at the edge: a case study with North American beaver
Authors: JAREMA STACEY I. , SAMSON JASON , MCGILL BRIAN J. , HUMPHRIES MURRAY M.
Published: October 2008

The absence of information about how abundance varies across species' ranges restricts most modeling and monitoring of climate change responses to the range edge. We examine spatial variation in abundance across the northeastern range of North American beaver (Castor canadensis), evaluate the extent to which climate and nonclimate variables explain this variation, and use a species–climate envelope model that includes spatial variation in abundance to predict beaver abundance responses to projected climate change. The density of beaver colonies across Québec follows a roughly logistic pattern, with high but variable density across the southern portion of the province, a sharp decline in density at about 49°N, and a long tail of low density extending as far as 58°N. Several climate and nonclimate variables were strong predictors of variation in beaver density, but 97% of the variation explained by nonclimate variables could be accounted for by climate variables. Because of the peak and tail density pattern, beaver climate sensitivity (change in density per unit change in climate) was greatest in the interior and lowest at the edge of the range. Combining our best density–climate models with projections from general circulation models (GCM) predicts a relatively modest expansion of the species' northern range limit by 2055, but density increases in the range interior that far exceed those at the range edge. Thus, some of the most dramatic responses to climate change may be occurring in the core of species' ranges, far away from the edge‐of‐the‐range focus of most current modeling and monitoring efforts.
Cross‐scale environmental influences on migratory stopover behaviour
Authors: CALVERT ANNA M. , TAYLOR PHILIP D. , WALDE SANDRA
Published: October 2008

Migratory species may be especially sensitive to climate change because their lifecycles are affected by dynamic ecological processes operating at global spatial scales. Insight into environmental effects upon en route decisions by migrants can therefore be a critical first step toward assessing their vulnerability to future climatic shifts. We extracted behaviour‐related parameters from a recent formulation of multistate mark–recapture models, and used them to evaluate the importance of variation in local weather and broad‐scale climate to decisions made by autumn passerine migrants at a coastal stopover site in Atlantic Canada. We found dramatic interannual fluctuations in the proportion of migrants that were transient (departing within a day of arrival), with annual average values ranging from 24% to 96% over the years 1996–2007. However, the relationships of stopover behaviour (transience and departure probability) to local weather (wind and precipitation) and to regional climatic fluctuations were similar across three distinct species groups and for birds of different fuel‐loads, indicating the potential for both immediate (day‐to‐day) and long‐term environmental influences (spanning several seasons). This cross‐scale approach contributes valuable information toward the conservation of migrants in the face of a changing climate by (i) quantifying environmental influences on stopover behaviour in broad temporal and geographic contexts, and (ii) demonstrating largely parallel interannual variation in stopover site‐use among birds with contrasting migratory timing and strategies.
Climate‐driven range extension of a sea urchin: inferring future trends by analysis of recent population dynamics
Authors: LING S. D. , JOHNSON C. R. , RIDGWAY K. , HOBDAY A. J. , HADDON M.
Published: October 2008

Patterns of climate‐forced range shift in the marine environment are informed by investigating the population dynamics of an ecologically important sea urchin (Centrostephanus rodgersii– Diadematidae) across its newly extended range in Tasmania (southeastern Australia). A growth model of C. rodgersii is developed allowing estimation of a sea urchin age profile and, in combination with abundance data, we correlate the sea urchin population dynamic with respect to environmental signals across the range extension region. Growth patterns did not vary across the extension region; however, there was a strong pattern of decreasing sea urchin age with increasing distance from the historic range. The sequential poleward discovery of the sea urchin, a pattern of declining age and a general poleward reduction in abundance along the eastern Tasmanian coastline are consistent with a model of range extension driven by recent change in patterns of larval dispersal. We explore this hypothesis by correlating C. rodgersii population characteristics with respect to the East Australian Current (EAC), i.e. the chief vector for poleward larval dispersal, and reveal patterns of declining sea urchin age and abundance with increasing distance from this oceanic feature. Furthermore, C. rodgersii is generally limited to sites where average winter temperatures are warmer than the cold threshold for its larval development. Potential dispersal and physiological mechanisms defining the range extension appear to be strongly coupled to the EAC which has undergone recent poleward advance and resulted in coastal warming in eastern Tasmania. Predicted climate change conditions for this region will favour continued population expansion of C. rodgersii not only via atmospheric‐forced ocean warming, but also via ongoing intensification of the EAC driving continued poleward supply of larvae and heat.