bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of specificity and magnitude of NF-κB and STAT1-mediated gene activation through PIASy and PIAS1 cooperation
Authors: Tahk Samuel , Liu Bin , Chernishof Vasili , Wong Kelly A. , Wu Hong , Shuai Ke
Published: July 2007

NF-κB and STATs regulate multiple cellular processes through the transcriptional activation of genes with diversified functions. Although the molecular mechanisms that can turn on/off the overall NF-κB/STAT signaling have been extensively studied, how NF-κB/STAT-target genes can be differentially regulated is poorly understood. Here we report that PIASy, a member of the PIAS (for protein inhibitor of activated STAT) protein family, is a physiologically important transcriptional repressor of NF-κB and STAT1.
Piasy
deletion in dendritic cells resulted in enhanced expression of a subset of NF-κB and STAT1-dependent genes in response to LPS or IFN-γ treatment, respectively. Consistently,
Piasy
null mice are hypersensitive to the LPS-induced endotoxic shock. Furthermore, PIASy and PIAS1 display specific as well as redundant effects on the regulation of NF-κB/STAT1 signaling.
Pias1
−/−
Piasy
−/−
embryos died before day 11.5. The disruption of one allele of
Pias1
in the
Piasy
−/−
background significantly enhanced the effect of
Piasy
deletion on the transcriptional induction of NF-κB/STAT1-dependent genes, and vice versa. Our results demonstrate that PIASy cooperates with PIAS1 to regulate the specificity and magnitude of NF-κB/STAT1-mediated gene activation.
Substrate-dependent transmembrane signaling in TonB-dependent transporters is not conserved
Authors: Kim Miyeon , Fanucci Gail E. , Cafiso David S.
Published: July 2007

Site-directed spin labeling (SDSL) was used to examine and compare transmembrane signaling events in the bacterial outer-membrane transport proteins BtuB, FecA, and FhuA. These proteins extract energy for transport by coupling to the transperiplasmic protein TonB, an interaction that is thought to be mediated by the Ton box, a highly conserved energy-coupling motif in these transporters. In the ferric citrate transporter, FecA, SDSL indicates that the Ton box undergoes a substrate-induced disorder transition similar to that seen for BtuB, the vitamin B
12
transporter. This conformational change produces an aqueous exposed, highly disordered protein fragment, which likely regulates transporter–TonB interactions. However, in the ferrichrome transporter, FhuA, SDSL does not reveal a substrate-induced unfolding transition. In this protein, with or without substrate, the Ton box conformation is found to be highly dynamic and constitutively unfolded. In addition, SDSL indicates that structural features seen in high-resolution models are not found in membrane-associated FhuA. Taken together, these data indicate that the Ton box of FhuA may always be available for interactions with TonB, implying that transporter–TonB interactions in FhuA are either constitutive or not regulated by the Ton box configuration.
Trehalose transporter 1, a facilitated and high-capacity trehalose transporter, allows exogenous trehalose uptake into cells
Authors: Kikawada Takahiro , Saito Ayako , Kanamori Yasushi , Nakahara Yuichi , Iwata Ken-ichi , Tanaka Daisuke , Watanabe Masahiko , Okuda Takashi
Published: July 2007

Trehalose is potentially a useful cryo- or anhydroprotectant molecule for cells and biomolecules such as proteins and nucleotides. A major obstacle to application is that cellular membranes are impermeable to trehalose. In this study, we isolated and characterized the functions of a facilitated trehalose transporter [trehalose transporter 1 (TRET1)] from an anhydrobiotic insect,
Polypedilum vanderplanki
.
Tret1
cDNA encodes a 504-aa protein with 12 predicted transmembrane structures.
Tret1
expression was induced by either desiccation or salinity stress. Expression was predominant in the fat body and occurred concomitantly with the accumulation of trehalose, indicating that TRET1 is involved in transporting trehalose synthesized in the fat body into the hemolymph. Functional expression of TRET1 in
Xenopus
oocytes showed that transport activity was stereochemically specific for trehalose and independent of extracellular pH (between 4.0 and 9.0) and electrochemical membrane potential. These results indicate that TRET1 is a trehalose-specific facilitated transporter and that the direction of transport is reversible depending on the concentration gradient of trehalose. The extraordinarily high values for apparent
K
m
(≥100 mM) and
V
max
(≥500 pmol/min per oocyte) for trehalose both indicate that TRET1 is a high-capacity transporter of trehalose. Furthermore, TRET1 was found to function in mammalian cells, suggesting that it confers trehalose permeability on cells, including those of vertebrates as well as insects. These characteristic features imply that TRET1 in combination with trehalose has high potential for basic and practical applications
in vivo
.
The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation
Authors: Banerjee Sulagna , Vishwanath Prashanth , Cui Jike , Kelleher Daniel J. , Gilmore Reid , Robbins Phillips W. , Samuelson John
Published: July 2007

Asn-linked glycans (N-glycans) play important roles in the quality control (QC) of glycoprotein folding in the endoplasmic reticulum (ER) lumen and in ER-associated degradation (ERAD) of proteins by cytosolic proteasomes. A UDP-Glc:glycoprotein glucosyltransferase glucosylates N-glycans of misfolded proteins, which are then bound and refolded by calreticulin and/or calnexin in association with a protein disulfide isomerase. Alternatively, an α-1,2-mannosidase (Mns1) and mannosidase-like proteins (ER degradation-enhancing α-mannosidase-like proteins 1, 2, and 3) are part of a process that results in the dislocation of misfolded glycoproteins into the cytosol, where proteins are degraded in the proteasome. Recently we found that numerous protists and fungi contain 0–11 sugars in their N-glycan precursors versus 14 sugars in those of animals, plants, fungi, and
Dictyostelium
. Our goal here was to determine what effect N-glycan precursor diversity has on N-glycan-dependent QC systems of glycoprotein folding and ERAD. N-glycan-dependent QC of folding (UDP-Glc:glycoprotein glucosyltransferase, calreticulin, and/or calnexin) was present and active in some but not all protists containing at least five mannose residues in their N-glycans and was absent in protists lacking Man. In contrast, N-glycan-dependent ERAD appeared to be absent from the majority of protists. However,
Trypanosoma
and
Trichomonas
genomes predicted ER degradation-enhancing α-mannosidase-like protein and Mns1 orthologs, respectively, each of which had α-mannosidase activity
in vitro
. Phylogenetic analyses suggested that the diversity of N-glycan-dependent QC of glycoprotein folding (and possibly that of ERAD) was best explained by secondary loss. We conclude that N-glycan precursor length has profound effects on N-glycan-dependent QC of glycoprotein folding and ERAD.
A comparative analysis of frog early development
Authors: del Pino Eugenia M. , Venegas-Ferrín Michael , Romero-Carvajal Andrés , Montenegro-Larrea Paola , Sáenz-Ponce Natalia , Moya Iván M. , Alarcón Ingrid , Sudou Norihiro , Yamamoto Shinji , Taira Masanori
Published: July 2007

The current understanding of
Xenopus laevis
development provides a comparative background for the analysis of frog developmental modes. Our analysis of development in various frogs reveals that the mode of gastrulation is associated with developmental rate and is unrelated to egg size. In the gastrula of the rapidly developing embryos of the foam-nesting frogs
Engystomops coloradorum
and
Engystomops randi
, archenteron and notochord elongation overlapped with involution at the blastopore lip, as in
X. laevis
embryos. In embryos of dendrobatid frogs and in the frog without tadpoles
Eleutherodactylus coqui
, which develop somewhat more slowly than
X. laevis
, involution and archenteron elongation concomitantly occurred during gastrulation; whereas elongation of the notochord and, therefore, dorsal convergence and extension, occurred in the postgastrula. In contrast, in the slow developing embryos of the marsupial frog
Gastrotheca riobambae
, only involution occurred during gastrulation. The processes of archenteron and notochord elongation and convergence and extension were postgastrulation events. We produced an Ab against the homeodomain protein Lim1 from
X. laevis
as a tool for the comparative analysis of development. By the expression of Lim1, we were able to identify the dorsal side of the
G. riobambae
early gastrula, which otherwise was difficult to detect. Moreover, the Lim1 expression in the dorsal lip of the blastopore and notochord differed among the studied frogs, indicating variation in the timing of developmental events. The variation encountered gives evidence of the modular character of frog gastrulation.
Cross‐curricular skills testing in The Netherlands
Authors: Meijer Joost
Published: July 2007

This article gives a description of three analyses concerning the construct learning to learn and the assessment of cross‐curricular skills. First, the correspondence between learning to learn and cross‐curricular skills is examined by means of a theoretical content analysis. Second, the nature of cross‐curricular skills is studied through a statistical analysis of the relation of these skills with intelligence, academic achievement and social‐affective measures. Third, differences in the mastery of cross‐curricular skills between two cohorts of students in Dutch secondary education were analysed statistically. The theoretical content analysis suggests that there are similarities between the learning to learn concept and cross‐curricular skills, but the correspondence may be moderate. Cross‐curricular skills appear to have more in common with academic achievement than with intelligence, suggesting that they are quite educable. Furthermore, they are moderately related to social‐affective characteristics. It appears that a cohort of Grade 9 students who were tested for their cross‐curricular skills in 1998 did considerably better compared to a cohort of Grade 9 students who were tested in 1996. There are some indications that this improvement may be related to the attention to these skills in schools.
Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function
Authors: Xiao Sheng , Najafian Nader , Reddy Jay , Albin Monica , Zhu Chen , Jensen Eric , Imitola Jaime , Korn Thomas , Anderson Ana C. , Zhang Zheng , Gutierrez Cristina , Moll Thomas , Sobel Raymond A. , Umetsu Dale T. , Yagita Hideo , Akiba Hisaya , Strom Terry , Sayegh Mohamed H. , DeKruyff Rosemarie H. , Khoury Samia J. , Kuchroo Vijay K.
Published: July 2007

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specific for Tim-1 and identified two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specific T cells, the production of the proinflammatory cytokines IFN-γ and IL-17, and the severity of experimental autoimmune encephalomyelitis. In contrast, another anti–Tim-1 antibody inhibited the generation of antigen-specific T cells, production of IFN-γ and IL-17, and development of autoimmunity, and it caused a strong Th2 response. Both antibodies bound to closely related epitopes in the IgV domain of the Tim-1 molecule, but the activating antibody had an avidity for Tim-1 that was 17 times higher than the inhibitory antibody. Although both anti–Tim-1 antibodies induced CD3 capping, only the activating antibody caused strong cytoskeletal reorganization and motility. These data indicate that Tim-1 regulates T cell responses and that Tim-1 engagement can alter T cell function depending on the affinity/avidity with which it is engaged.
Distinct roles for Syk and ZAP-70 during early thymocyte development
Authors: Palacios Emil H. , Weiss Arthur
Published: July 2007

The spleen tyrosine kinase (Syk) and ζ-associated protein of 70 kD (ZAP-70) tyrosine kinases are both expressed during early thymocyte development, but their unique thymic functions have remained obscure. No specific role for Syk during β-selection has been established, and no role has been described for ZAP-70 before positive selection. We show that Syk and ZAP-70 provide thymocytes with unique and separable fitness advantages during early development. Syk-deficient, but not ZAP-70–deficient, thymocytes are specifically impaired in initial pre-TCR signaling at the double-negative (DN) 3 β selection stage and show reduced cell-cycle entry. Surprisingly, and despite overlapping expression of both kinases, only ZAP-70 appears to promote sustained pre-TCR/TCR signaling during the DN4, immature single-positive, and double-positive stages of development before thymic selection occurs. ZAP-70 promotes survival and cell-cycle progression of developing thymocytes before positive selection, as also shown by in vivo anti-CD3 treatment of recombinase-activating gene 1–deficient mice. Our results establish a temporal separation of Syk family kinase function during early thymocyte development and a novel role for ZAP-70. We propose that pre-TCR signaling continues during DN4 and later stages, with ZAP-70 dynamically replacing Syk for continued pre-TCR signaling.
Relative time scales reveal multiple origins of parallel disjunct distributions of African caecilian amphibians
Authors: Loader Simon P , Pisani Davide , Cotton James A , Gower David J , Day Julia J , Wilkinson Mark
Published: July 2007

Parallel patterns of distribution in different lineages suggest a common cause. Explanations in terms of a single biogeographic event often imply contemporaneous diversifications. Phylogenies with absolute time scales provide the most obvious means of testing temporal components of biogeographic hypotheses but, in their absence, the sequence of diversification events and whether any could have been contemporaneous can be tested with relative date estimates. Tests using relative time scales have been largely overlooked, but because they do not require the calibration upon which absolute time scales depend, they make a large amount of existing molecular data of use to historical biogeography and may also be helpful when calibration is possible but uncertain. We illustrate the use of relative dating by testing the hypothesis that parallel, disjunct east/west distributions in three independent lineages of African caecilians have a common cause. We demonstrate that at least two biogeographic events are implied by molecular data. Relative dating analysis reveals the potential complexity of causes of parallel distributions and cautions against inferring common cause from common spatial patterns without considering the temporal dimension.
Increase of heterozygosity in a growing population of lesser kestrels
Authors: Ortego Joaquín , Aparicio José Miguel , Calabuig Gustau , Cordero Pedro J
Published: July 2007

The lesser kestrel (
Falco naumanni
) suffered a sharp population decline over much of its European distribution range in the middle of the twentieth century. Still declining in some areas, the species has recently experienced a notable population recovery in certain regions. We examined the genetic diversity variation in a growing population of lesser kestrels from Central Spain over a 6-year period (2000–2005). The population studied showed a rapid demographic expansion, increasing in the number of both breeding pairs and colonies. Annual average heterozygosity and allelic diversity increased and genetic similarity between potential mates decreased over the study period. Several immigrants regularly arrived in the study area and introduced new alleles into the local population, pointing to immigration as the main cause contributing to the observed genetic recovery.
Muscle performance in a soft-bodied terrestrial crawler: constitutive modelling of strain-rate dependency
Authors: Dorfmann A. Luis , Woods William A , Trimmer Barry A
Published: July 2007

Experimental data on the passive mechanical properties of the ventral interior lateral muscle of the tobacco hornworm caterpillar,Manduca sexta, are reported. The stress–deformation response of theManducamuscle is shown to be nonlinear pseudo-elastic, capable of large deformations and subject to stress softening during initial loading cycles. The muscle passive mechanical properties also depend on multiple time-dependent processes. In particular, we show new experimental data from cyclic loading tests of an unstimulated muscle with constant maximum stretch and different, constant engineering strain rates. Then, on the basis of these data a constitutive model is derived to reproduce the main characteristics of this behaviour. In formulating the constitutive model, we consider the muscle as a complex macromolecular structure with fibrous components at numerous size scales. The model uses a phenomenological approach to account for different mechanisms by which passive force changes during applied deformation and how the muscle properties recover after unloading.
The Society of Arts and Joseph Banks: a first step in London learned society
Authors: Chambers N.A
Published: July 2007

Joseph Banks (1743–1820) was President of the Royal Society from 1778 to 1820, the longest anyone has served in that capacity, and during his prolonged tenure Banks was elected to numerous other societies at home and abroad. In the present paper Banks's membership of the Society of Arts and Manufactures is discussed, this being the first society to which he was ever elected in 1761. Of particular interest are the previously unexplained reasons for his withdrawal from the society in 1764, and his eventual re-election in 1791, this being the only example of Banks leaving and then rejoining a society. These events are investigated here. The creation, purpose and early development of the Society of Arts are also considered, as is its membership at a time when subscriptions were falling in the 1760s. Links with the Royal Society are described before, during and after this period of decline, and Joseph Banks's own contribution to the work of the Society of Arts is outlined.
The Royal Society's Glass Workers' Cataract Committee; Sir William Crookes and the development of sunglasses
Authors: Brock William H
Published: July 2007

After the inclusion of a number of industrial diseases and injuries in the Workmen's Compensation Acts of 1896 and 1906, the government asked the Royal Society to investigate how and why glare and heat apparently caused glassworkers to develop cataracts during their working lives. The activities between 1908 and 1928 of the Glass Workers' Cataract Committee, which was made up of chemists, physiologists and ophthalmologists, are discussed. Emphasis is placed on the attempts by the octogenarian William Crookes (PRS 1913–15) to formulate a spectacle glass that was opaque to infrared and ultraviolet radiation. While providing relief for industrial workers, the research also laid the foundation for the modern sunglasses industry. Other significant work of the Committee concerned the biochemistry of the eye.
John Couch Adams's Asperger syndrome and the British non-discovery of Neptune
Authors: Sheehan William , Thurber Steven
Published: July 2007

We discuss the mathematical acumen of John Couch Adams together with cognitive and behavioural characteristics that suggest Asperger syndrome. We also review the historical events involved in the investigation of the unknown planet thought to be affecting the orbital motion of Uranus. Adams produced a vital computation necessary for the discovery of Neptune that was insufficient unless integrated with specialized knowledge of other members of a British ‘team’ and then presented formally to the scientific community. Reasoning from the premise that complex scientific discoveries often involve cooperative social dynamics, we conclude that Adams was precluded from sharing his contribution in a collaborative manner, in part, because of empathic and social communication deficiencies related to his disorder. However, it was a ‘team’ failure, not Adams's alone.
Transcriptome profiling of the response of Mycosphaerella graminicola isolates to an azole fungicide using cDNA microarrays
Authors: COOLS HANS J. , FRAAIJE BART A. , BEAN TIM P. , ANTONIW JOHN , LUCAS JOHN A.
Published: July 2007

Resistance to azole antifungals is a major problem in the control of diseases caused by fungal pathogens of both humans and plants. Potential for the development of azole resistance in the wheat leaf blotch pathogen Mycosphaerella graminicola, the causal agent of the most economically significant foliar disease of wheat in north‐western Europe, is now of particular concern after the recent emergence of widespread resistance to quinone outside inhibitor fungicides. Using a cDNA microarray representing around 25% of the genome, we have profiled the transcriptional response of M. graminicola to epoxiconazole, currently the most widely used azole fungicide on cereal crops. By comparing the transcription profiles of two M. graminicola isolates with contrasting sensitivities to epoxiconazole we show qualitative and quantitative differences in differentially expressed genes, including those involved in ergosterol biosynthesis, mitochondrial respiration and transport mechanisms. This represents the first study investigating the response of a plant pathogenic fungus to a fungicide using cDNA microarray technology.
Relationship between glutathione S‐transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics
Authors: Mak J. C. W. , Ho S. P. , Leung H. C. M. , Cheung A. H. K. , Law B. K. W. , So L. K. Y. , Chan J. W. M. , Chau C. H. , Lam W. K. , Ip M. S. M. , Chan‐Yeung M.
Published: July 2007

Background
Asthma is a disease associated with oxidative stress. The glutathione S‐transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported.

Objective
To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults.

Methods
An age‐ and smoking status‐matched case–control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR‐RFLP). Plasma GST activity was measured by fluorometric assay.

Results
The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34–0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001).

Conclusion
Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.
Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding
Authors: Fusaro Ana E. , Brito Cyro A. , Victor Jefferson R. , Rigato Paula O. , Goldoni Adriana L. , Duarte Alberto J. S. , Sato Maria N.
Published: July 2007

Allergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen‐specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non‐specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.
Interleukin‐6 is responsible for aberrant B‐cell receptor‐mediated regulation of RAG expression in systemic lupus erythematosus
Authors: Hillion Sophie , Garaud Soizic , Devauchelle Valérie , Bordron Anne , Berthou Christian , Youinou Pierre , Jamin Christophe
Published: July 2007

Defective regulation of secondary immunoglobulin V(D)J gene rearrangement promotes the production of autoantibodies in systemic lupus erythematosus (SLE). It remains unclear, however, whether the regulation of the recombination‐activating genes RAG1 and RAG2 is effective in SLE. RAG1 and RAG2 messenger RNA expression was analysed before and after in vitro activation of sorted CD19+ CD5– B cells with anti‐immunoglobulin M antibodies, in 20 SLE patients and 17 healthy controls. The expression of CDK2 and p27Kip1 regulators of the RAG2 protein, were examined. The levels of interleukin‐6 (IL‐6) and its influence on RAG regulation were also evaluated in vitro. SLE patients had increased frequency of RAG‐positive B cells. B‐cell receptor (BCR) engagement induced a shift in the frequency of κ‐ and λ‐positive cells, associated with a persistence of RAG messenger RNA and the maintenance of RAG2 protein within the nucleus. While expression of the RAG2‐negative regulator CDK2 was normal, the positive regulator p27Kip1 was up‐regulated and enhanced by BCR engagement. This effect was the result of the aberrant production of IL‐6 by SLE B cells. Furthermore, IL‐6 receptor blockade led to a reduction in p27Kip1 expression, and allowed the translocation of RAG2 from the nucleus to the cytoplasm. Our study indicates that aberrant production of IL‐6 contributes to the inability of SLE B cells to terminate RAG protein production. Therefore, we hypothesize that because of constitutive IL‐6 signalling in association with BCR engagement, SLE B cells would become prone to secondary immunoglobulin gene rearrangements and autoantibody production.
Evidence for size and sex‐specific dispersal in a cooperatively breeding cichlid fish
Authors: STIVER K. A. , DESJARDINS J. K. , FITZPATRICK J. L. , NEFF B. , QUINN J. S. , BALSHINE S.
Published: July 2007

African Great Lake cichlid populations are divided into thousands of genetic subpopulations. The low gene flow between these subpopulations is thought to result from high degrees of natal philopatry, heavy predation pressure, and a patchy distribution of preferred habitats. While predation pressure and habitat distribution are fairly straightforward to assess, data on dispersal distances and rates are scarce. In fishes, direct observations of dispersal events are unlikely, but dispersal can be studied using molecular markers. Using seven microsatellite loci, we examined dispersal in the cooperatively breeding cichlid fish, Neolamprologus pulcher. As this species is found in well‐defined groups clustered into subpopulations, we could assess dispersal on a narrow (within subpopulation) and broad (between subpopulation) scale. While fish were generally more related to others in their own subpopulation than they were to fish from other subpopulations, large males diverged from this pattern. Large males were more related to other large males from different subpopulations than they were to large males from their own subpopulation, suggesting more frequent dispersal by large males. Across subpopulations, relatedness between large males was higher than the relatedness among large females; this pattern was not detected in small males and small females. Within a subpopulation, individuals appeared to be preferentially moving away from relatives, and movement was unrestricted by the physical distance between groups. Our results highlight the importance of examining multiple spatial scales when studying individual dispersal biases.
Within‐population variation in prevalence and lineage distribution of avian malaria in blue tits, Cyanistes caeruleus
Authors: WOOD MATTHEW J. , COSGROVE CATHERINE L. , WILKIN TEDDY A. , KNOWLES SARAH C. L. , DAY KAREN P. , SHELDON BEN C.
Published: July 2007

The development of molecular genetic screening techniques for avian blood parasites has revealed many novel aspects of their ecology, including greatly elevated diversity and complex host–parasite relationships. Many previous studies of malaria in birds have treated single study populations as spatially homogeneous with respect to the likelihood of transmission of malaria to hosts, and we have very little idea whether any spatial heterogeneity influences different malaria lineages similarly. Here, we report an analysis of variation in the prevalence and cytochrome b lineage distribution of avian malaria infection with respect to environmental and host factors, and their interactions, in a single blue tit (Cyanistes caeruleus) population. Of 11 Plasmodium and Haemoproteus cytochrome b lineages found in 997 breeding individuals, the three most numerous (pSGS1, pTURDUS1 and pBT7) were considered separately, in addition to analyses of all avian malaria lineages pooled. Our analyses revealed marked spatial differences in the prevalence and distribution of these lineages, with local prevalence of malaria within the population ranging from over 60% to less than 10%. In addition, we found several more complex patterns of prevalence with respect to local landscape features, host state, parasite genotype, and their interactions. We discuss the implications of such heterogeneity in parasite infection at a local scale for the study of the ecology and evolution of infectious diseases in natural populations. The increased resolution afforded by the combination of molecular genetic and geographical information systems (GIS) tools has the potential to provide many insights into the epidemiology, evolution and ecology of these parasites in the future.
Evolutionary mechanisms shaping the genetic population structure of marine fishes; lessons from the European flounder (Platichthys flesus L.)
Authors: HEMMER‐HANSEN JAKOB , NIELSEN EINAR EG , GRØNKJÆR PETER , LOESCHCKE VOLKER
Published: July 2007

A number of evolutionary mechanisms have been suggested for generating low but significant genetic structuring among marine fish populations. We used nine microsatellite loci and recently developed methods in landscape genetics and coalescence‐based estimation of historical gene flow and effective population sizes to assess temporal and spatial dynamics of the population structure in European flounder (Platichthys flesus L.). We collected 1062 flounders from 13 localities in the northeast Atlantic and Baltic Seas and found temporally stable and highly significant genetic differentiation among samples covering a large part of the species’ range (global FST = 0.024, P < 0.0001). In addition to historical processes, a number of contemporary acting evolutionary mechanisms were associated with genetic structuring. Physical forces, such as oceanographic and bathymetric barriers, were most likely related with the extreme isolation of the island population at the Faroe Islands. A sharp genetic break was associated with a change in life history from pelagic to benthic spawners in the Baltic Sea. Partial Mantel tests showed that geographical distance per se was not related with genetic structuring among Atlantic and western Baltic Sea samples. Alternative factors, such as dispersal potential and/or environmental gradients, could be important for generating genetic divergence in this region. The results show that the magnitude and scale of structuring generated by a specific mechanism depend critically on its interplay with other evolutionary mechanisms, highlighting the importance of investigating species with wide geographical and ecological distributions to increase our understanding of evolution in the marine environment.
A role for type I signal peptidase in Staphylococcus aureus quorum sensing
Authors: Kavanaugh Jeffrey S. , Thoendel Matthew , Horswill Alexander R.
Published: July 2007

The Staphylococcus aureus Agr quorum‐sensing system modulates the expression of extracellular virulence factors. The Agr system is controlled by an autoinducing peptide (AIP) molecule that is secreted during growth. In the AIP biosynthetic pathway, two proteolytic events are required to remove the leader and tail segments of AgrD, the peptide precursor of AIP. The only protein known to be involved in this pathway is AgrB, a membrane endopeptidase that removes the AgrD carboxy‐tail. We designed a synthetic peptide substrate and developed an assay to detect peptidases that can remove the N‐terminal leader of AIP. Several peptidase activities were detected in S. aureus extracts and these activities were present in both wild‐type and agr mutant strains. Only one of these peptidases cleaved in the correct position and all properties of this enzyme were consistent with type I signal peptidase. Subsequent cloning and purification of the two known S. aureus signal peptidases, SpsA and SpsB, demonstrated that only SpsB catalysed this activity in vitro. To investigate the role of SpsB in AIP biosynthesis, SpsB peptide inhibitors were designed and characterized. The most effective inhibitor blocked SpsB activity in vitro and showed antibacterial activity against S. aureus. Importantly, the inhibitor reduced expression of an Agr‐dependent reporter and inhibited AIP production in S. aureus, indicating a role for SpsB in quorum sensing.
Optimal time for therapeutic drug monitoring of cyclosporine microemulsion in patients with psoriasis
Authors: Umezawa Yoshinori , Ozawa Akira
Published: July 2007

Background  The clinical usefulness of cyclosporine in patients with psoriasis has generally been established; however, modification of the dosage on the basis of therapeutic drug monitoring is needed to prevent potential adverse reactions. The area under the drug concentration–time curve from 0 to 4 h after treatment (AUC0−4), used to assess the pharmacokinetics of cyclosporine microemulsion, correlates with clinical symptoms and adverse reactions.

Methods  In order to evaluate the blood collection times after oral treatment that are most relevant to pharmacokinetics, we examined the pharmacokinetics of cyclosporine up to 4 h after treatment in 24 patients with psoriasis vulgaris who received an oral dose of 3.0 mg/kg of cyclosporine microemulsion (Neoral®) daily in two divided doses.

Results  Our results showed that the blood concentration of cyclosporine 2 h after treatment (C2) correlated with AUC0−4 (r = 0.89, P < 0.001).

Conclusions  C
2 should be monitored in patients treated with cyclosporine microemulsion instead of the blood trough level immediately before treatment, which has conventionally been used to monitor cyclosporine concentrations in blood.
Papular follicular eruptions in human immunodeficiency virus‐positive patients in South Africa
Authors: Budavari Judith M. , Grayson Wayne
Published: July 2007

Background  Papular and follicular eruptions, such as papulopruritic eruption, eosinophilic folliculitis, and infective folliculitis, are relatively common disorders in patients infected with the human immunodeficiency virus (HIV). These conditions may show considerable clinical overlap.

Objective  To assess the relative proportion of pruritic papular cutaneous eruptions in South Africans with HIV‐associated dermatoses, and to correlate the clinical and histologic features of these lesions.

Methods  The clinical and histologic features of papular follicular eruptions were correlated in 40 consecutive black HIV‐positive patients who underwent skin biopsy.

Results  The clinical features were similar in all patients and consisted of widespread papules and pustules involving the face, limbs, and trunk. The most common histologic finding was acute suppurative folliculitis, seen in 27 patients (67.5%). In most cases, no cause was found for the suppuration. Papulopruritic eruption of HIV was diagnosed in six patients (15%), HIV‐associated eosinophilic folliculitis in four (10%), Pityrosporum folliculitis in two (5%), and acne in one (2.5%). Concordance between the initial clinical diagnosis and the final histopathologic diagnosis was achieved in only 27.5% of cases.

Conclusion  Skin biopsy remains an important adjunct to the correct diagnosis and classification of papular and follicular eruptions in HIV‐positive patients.
Pseudoepitheliomatous hyperplasia – an unusual reaction following tattoo: report of a case and review of the literature
Authors: Cui Wei , McGregor Douglas H. , Stark Steven P. , Ulusarac Ozlem , Mathur Sharad C.
Published: July 2007

A 59‐year‐old woman presented with an itchy and uncomfortable raised lesion at a tattoo site (Fig. 1) on the lateral aspect of the left leg, just above the ankle. The tattoo had been placed 2 years before her presentation and the tattoo site was sun exposed. Immediately after she had the tattoo, she noticed redness of the skin. After a week, a pruritic and red scaly nodule developed that continued to gradually enlarge until her presentation. The patient had tried topical vitamin A and D ointment with no relief. The patient also had tattoos on the arms without any noticeable skin changes. The patient reported that the tattoo procedure on her leg was more painful than that on her arms, and was performed by a different (and perhaps inexperienced) tattoo artist. The original tattoo contained red, green, and yellow pigments.

Raised nodular lesion with irregular margins

image

A diagnosis of tattoo granuloma was considered; squamous cell carcinoma and fungal infection were included in the differential diagnosis. A punch biopsy was performed, followed by complete surgical excision of the lesion with a split‐thickness skin graft from the right thigh.

The skin excision specimen showed a 3 × 2.5‐cm granular and pitted pink lesion with well‐demarcated, somewhat irregular borders. The lesion was raised 0.5 cm above the skin surface. The lesion was present in the center of the original tattoo. Portions of the original tattoo with green and blue–green pigmentation were visible on either side of the lesion. No satellite lesions were identified.

Microscopically, the raised lesion demonstrated striking pseudoepitheliomatous hyperplasia, with irregular acanthosis of the epidermis and follicular infundibula, hyperkeratosis, and parakeratosis (Fig. 2). Follicular plugging was present with keratin‐filled cystic spaces. There was a brisk mononuclear inflammatory infiltrate in the dermis, composed primarily of lymphocytes, with admixed plasma cells and histiocytes. Giant cells were occasionally identified. Dermal pigment deposition was noted both within the lesion and in the surrounding skin, corresponding to the original tattoo. Variable dermal fibrosis was noted, with thick collagen bundles in some areas. There was no evidence of epidermal keratinocytic atypia, dyskeratosis, or increased suprabasal mitotic activity. Special stains (periodic acid–Schiff and acid‐fast) for microorganisms were negative.

(a) Raised lesion with marked pseudoepitheliomatous hyperplasia and follicular plugging (hematoxylin and eosin; magnification, ×2.5). (b) Irregularly elongated and thickened rete pegs with blunt ends associated with dermal chronic inflammation (hematoxylin and eosin; magnification, ×5). (c) Follicular dilation and plugging with keratin‐filled cystic spaces (hematoxylin and eosin; magnification, ×5). (d) Dermal pigment and fibrosis (hematoxylin and eosin; magnification, ×10)

image
Molecular evidence of Pleistocene bidirectional faunal exchange between Europe and the Near East: the case of the bicoloured shrew (Crocidura leucodon, Soricidae)
Authors: DUBEY S. , COSSON J.‐F. , VOHRALÍK V. , KRYŠTUFEK B. , DIKER E. , VOGEL P.
Published: July 2007

We sequenced 1077 bp of the mitochondrial cytochrome b gene and 511 bp of the nuclear Apolipoprotein B gene in bicoloured shrew (Crocidura leucodon, Soricidae) populations ranging from France to Georgia. The aims of the study were to identify the main genetic clades within this species and the influence of Pleistocene climatic variations on the respective clades. The mitochondrial analyses revealed a European clade distributed from France eastwards to north‐western Turkey and a Near East clade distributed from Georgia to Romania; the two clades separated during the Middle Pleistocene. We clearly identified a population expansion after a bottleneck for the European clade based on mitochondrial and nuclear sequencing data; this expansion was not observed for the eastern clade. We hypothesize that the western population was confined to a small Italo‐Balkanic refugium, whereas the eastern population subsisted in several refugia along the southern coast of the Black Sea.
Convergence of cutaneous, musculoskeletal, dural and visceral afferents onto nociceptive neurons in the first cervical dorsal horn
Authors: Mørch C. D. , Hu J. W. , Arendt‐Nielsen L. , Sessle B. J.
Published: July 2007

The convergence of cutaneous, musculoskeletal, dural and visceral afferents onto nociceptive neurons in the first cervical dorsal horn was investigated in urethane/chloralose‐anesthetized rats. Electrical stimulation was applied to facial, neck, shoulder and forepaw skin, cornea (COR), dura, second cervical (C2) nerve, hypoglossal nerve, temporomandibular joint, masseter (MAS) muscle and superior laryngeal nerve. In addition, acetic acid was injected intraperitoneally and microinjection of glutamate was applied to the tongue, MAS muscle, splenius cervicis muscle, dura and intrapericardial area. A total of 52 nociceptive neurons classified as wide dynamic range (n = 28) or nociceptive‐specific (n = 24) was studied. All nociceptive neurons received afferent input from the skin and at least one COR, musculoskeletal, dural or visceral afferent source in the trigeminal (V) or cervical area but input from afferent sources caudal to the C2 innervation territory was sparse. The proportion of neurons responding to COR, dural, C2 nerve, hypoglossal nerve, temporomandibular joint, MAS muscle and superior laryngeal nerve stimulations was 87, 54, 85, 52, 73, 64 and 31%, respectively. Electrical stimulation of all tested sites showed a double logarithmic stimulus–response relation, and cluster analysis of the excitability to COR, musculoskeletal, dural and visceral stimulations revealed two groups of neurons, one mainly containing wide dynamic range neurons and one mainly containing nociceptive‐specific neurons. These findings indicate that afferent convergence in first cervical dorsal horn nociceptive neurons may be limited to the craniofacial area and that they may play an important role in the integration of craniofacial and upper cervical nociceptive inputs.
Granulocyte colony‐stimulating factor has a negative effect on stroke outcome in a murine model
Authors: Taguchi Akihiko , Wen Zhongmin , Myojin Kazunori , Yoshihara Tomoyuki , Nakagomi Takayuki , Nakayama Daisuke , Tanaka Hidekazu , Soma Toshihiro , Stern David M. , Naritomi Hiroaki , Matsuyama Tomohiro
Published: July 2007

The administration of CD34‐positive cells after stroke has been shown to have a beneficial effect on functional recovery by accelerating angiogenesis and neurogenesis in rodent models. Granulocyte colony‐stimulating factor (G‐CSF) is known to mobilize CD34‐positive cells from bone marrow and has displayed neuroprotective properties after transient ischemic stress. This led us to investigate the effects of G‐CSF administration after stroke in mouse. We utilized permanent ligation of the M1 distal portion of the left middle cerebral artery to develop a reproducible focal cerebral ischemia model in CB‐17 mice. Animals treated with G‐CSF displayed cortical atrophy and impaired behavioral function compared with controls. The negative effect of G‐CSF on outcome was associated with G‐CSF induction of an exaggerated inflammatory response, based on infiltration of the peri‐infarction area with CD11b‐positive and F4/80‐positive cells. Although clinical trials with G‐CSF have been started for the treatment of myocardial and limb ischemia, our results indicate that caution should be exercised in applying these results to cerebral ischemia.
Enterocele repair by abdominal obliteration of the pelvic inlet: long‐term outcome on obstructed defaecation and symptoms of pelvic discomfort
Authors: Oom D. M. J. , Van Dijl V. R. M. , Gosselink M. P. , Van Wijk J. J. , Schouten W. R.
Published: July 2007

Objective  Enterocele is defined as a herniation of the peritoneal sac between the vagina and the rectum. This may contain either sigmoid colon or small bowel. It has been reported that enterocele is associated with obstructed defaecation and symptoms of pelvic discomfort. The aim of the present study was to evaluate the long‐term effect of enterocele repair.

Method  In the time period between 1994 and 2003, 54 women (median age 54 years; range: 31–80) with a symptomatic enterocele underwent obliteration of the pelvic inlet with a U‐shaped Mersilene® mesh. All patients underwent evacuation proctography (EP), which was repeated 6 months after the repair. In addition, they were contacted over the telephone to assess the long‐term effect of enterocele repair. Forty‐nine patients were willing to answer questions over the telephone. Five patients were lost to follow‐up (response rate: 91%).

Results  Six months after the procedure, EP revealed a recurrent or persistent enterocele in five (9%) patients, which was symptomatic in two, both of whom underwent a second repair. Among the 49 patients without an enterocele after 6 months, 10 (23%) women encountered recurrent symptoms of pelvic discomfort at a median follow‐up of 85 months (range: 3–137). Despite adequate correction of the enterocele, obstructed defaecation persisted in 21 (75%) patients of 28, who presented with this problem before the procedure. De novo dyspareunia occurred in 5% of the women after the procedure.

Conclusion  Obliteration of the pelvic inlet with a U‐shaped Mersilene® mesh provides an effective tool for anatomical correction of enteroceles. However, in the long term one of four patients encounters recurrent symptoms of pelvic discomfort. It seems unlikely that enterocele contributes to obstructed defaecation, as evacuation difficulties persist in around three quarters of the patients.