bluuebunny/crossref_metadata_2025 huggingface dataset:
PHYTOCHROME KINASE SUBSTRATE 1 is a phototropin 1 binding protein required for phototropism
Authors: Lariguet Patricia , Schepens Isabelle , Hodgson Daniel , Pedmale Ullas V. , Trevisan Martine , Kami Chitose , de Carbonnel Matthieu , Alonso José M. , Ecker Joseph R. , Liscum Emmanuel , Fankhauser Christian
Published: June 2006

Phototropism, or plant growth in response to unidirectional light, is an adaptive response of crucial importance. Lateral differences in low fluence rates of blue light are detected by phototropin 1 (phot1) in
Arabidopsis
. Only NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and root phototropism 2, both belonging to the same family of proteins, have been previously identified as phototropin-interacting signal transducers involved in phototropism. PHYTOCHROME KINASE SUBSTRATE (PKS) 1 and PKS2 are two phytochrome signaling components belonging to a small gene family in
Arabidopsis
(
PKS1
–
PKS4
). The strong enhancement of
PKS1
expression by blue light and its light induction in the elongation zone of the hypocotyl prompted us to study the function of this gene family during phototropism. Photobiological experiments show that the PKS proteins are critical for hypocotyl phototropism. Furthermore, PKS1 interacts with phot1 and NPH3
in vivo
at the plasma membrane and
in vitro
, indicating that the PKS proteins may function directly with phot1 and NPH3 to mediate phototropism. The phytochromes are known to influence phototropism but the mechanism involved is still unclear. We show that PKS1 induction by a pulse of blue light is phytochrome A-dependent, suggesting that the PKS proteins may provide a molecular link between these two photoreceptor families.
Transcription of ribosomal genes can cause nondisjunction
Authors: Machín Felix , Torres-Rosell Jordi , De Piccoli Giacomo , Carballo Jesús A. , Cha Rita S. , Jarmuz Adam , Aragón Luis
Published: June 2006

Mitotic disjunction of the repetitive ribosomal DNA (rDNA) involves specialized segregation mechanisms dependent on the conserved phosphatase Cdc14. The reason behind this requirement is unknown. We show that rDNA segregation requires Cdc14 partly because of its physical length but most importantly because a fraction of ribosomal RNA (rRNA) genes are transcribed at very high rates. We show that cells cannot segregate rDNA without Cdc14 unless they undergo genetic rearrangements that reduce rDNA copy number. We then demonstrate that cells with normal length rDNA arrays can segregate rDNA in the absence of Cdc14 as long as rRNA genes are not transcribed. In addition, our study uncovers an unexpected role for the replication barrier protein Fob1 in rDNA segregation that is independent of Cdc14. These findings demonstrate that highly transcribed loci can cause chromosome nondisjunction.
The Changes in Ca2+ Sparks Associated with Measured Modifications of Intra-store Ca2+ Concentration in Skeletal Muscle
Authors: Launikonis Bradley S. , Zhou Jingsong , Santiago Demetrio , Brum Gustavo , Ríos Eduardo
Published: June 2006

In cardiac muscle and amphibian skeletal muscle, the intracellular Ca2+ release that signals contractile activation proceeds by discrete local packets, which result in Ca2+ sparks. The remarkably stereotyped duration of these release events requires a robustly timed termination mechanism. In cardiac muscle the mechanism of spark termination appears to crucially involve depletion of Ca2+ in the lumen of the sarcoplasmic reticulum (SR), but in skeletal muscle, the mechanism is unknown. We used SEER (shifted excitation and emission ratioing of fluorescence) of SR-trapped mag-indo-1 and confocal imaging of fluorescence of cytosolic rhod-2 to image Ca2+ sparks while reversibly changing and measuring [Ca2+] in the SR ([Ca2+]SR) of membrane-permeabilized frog skeletal muscle cells. Sparks were collected in cells immersed in a solution promoting production of events at moderate frequency. Just after permeabilization, event frequency was zero, and in 10 minutes it reached close to a steady value. Controlled interventions modified [Ca2+]SR reversibly between a low value (299 μM on average in 10 experiments) and a high value (433 μM, a 45% average increase). This change increased sparks frequency by 93%, spatial width by 7%, rise time by 10%, and peak amplitude by 38% (provided that it was calculated in absolute terms, rather than normalized by resting fluorescence). The changes in event frequency and amplitude were statistically significant. The “strength” of the effect of [Ca2+]SR on frequency, quantified by decomposition of variance, was <6%. While the average change in [Ca2+]SR was limited, it reached up to 200% in individual fibers, without causing massive Ca2+ release or an increase of >3.5-fold in event frequency. Taken together with existing evidence that depletion is modest during Ca2+ sparks or release elicited by an action potential, the mild effects of [Ca2+]SR reported here do not support a major role of depletion in either the termination of sparks or the strong inactivation that terminates Ca2+ release at the global level in frog skeletal muscle.
Toward a Pluralistic Vision of Methodology
Authors: Brady Henry E. , Collier David , Seawright Jason
Published: June 2006

The discussion of qualitative and quantitative research methods in political science has followed a “long arc of development,” according to Andrew Bennett (this symposium). He sees our bookRethinking Social Inquiry: Diverse Tools, Standards(RSI) as a “key turning point” in this development and as contributing to a more pluralistic vision of methodology. We would certainly be gratified if we have indeed made this contribution. Yet this is an ongoing discussion, and this symposium points to fruitful directions this discussion can take.
Evaluation of the immunogenicity of the P97R1 adhesin of Mycoplasma hyopneumoniae as a mucosal vaccine in mice
Authors: Chen Austen Y. , Fry Scott R. , Forbes-Faulkner Judy , Daggard Grant , Mukkur T. K. S.
Published: June 2006

The immunogenicity of P97 adhesin repeat region R1 (P97R1) ofMycoplasma hyopneumoniae, an important pathogenesis-associated region of P97, was evaluated in mice as a mucosal vaccine. Mice were immunized orally with attenuatedSalmonella typhimurium aroAstrain CS332 harbouring a eukaryotic or prokaryotic expression vector encoding P97R1. Local and systemic immune responses were analysed by ELISA on mouse sera, lung washes and splenocyte supernatants following splenocyte stimulation with specific antigensin vitro. Although no P97R1-specific antibody responses were detected in serum and lung washes, significant gamma interferon was produced by P97R1-stimulated splenocytes from mice immunized orally withS. typhimurium aroAharbouring either expression system, indicating induction of a cell-mediated immune response. These results suggested that live bacterial vectors carrying DNA vaccines or expressing heterologous antigens preferentially induce a Th1 response. Surprisingly, however, mice immunized with the vaccine carrierS. typhimurium aroACS332 induced serum IgG, but not mucosal IgA, against P97R1 orS. typhimurium aroACS332 whole-cell lysate, emphasizing the importance of assessing the suitability of attenuatedS. typhimuriumantigen-carrier delivery vectors in the mouse model prior to their evaluation as potential vaccines in the target species, which in this instance was pigs.
Protean clinical manifestations and diagnostic challenges of human brucellosis in adults: 16 years' experience in an endemic area
Authors: Mantur Basappa G. , Biradar Mallanagouda S. , Bidri Rajendra C. , Mulimani Mallanna S. , K. Veerappa , Kariholu Piaraylal , Patil Siddanagouda B. , Mangalgi Smita S.
Published: June 2006

A prospective study was carried out to elucidate the clinical, epidemiological and laboratory features of human brucellosis. A total of 26 948 blood samples (from adults aged 15 years and above) were screened for serological evidence of brucellosis over a period of 16 years. The slide agglutination/Rose Bengal plate agglutination test gave positive results in 517 patients, of which 509 had detectable titres by the standard tube agglutination test (SAT). The diagnosis of brucellosis was documented in 495 (1.8 %) patients based on diagnostic titres (⩾1 : 160, 490 cases) and rising titres from insignificant titres (four cases) by serology and for one case by blood-culture isolation alone. Blood cultures were carried out in 345 cases, of which 191 cases (55.3 %) yieldedBrucella melitensis. In 77/79 cases undertaken for follow up, there was a steady fall in 2-mercaptoethanol (2ME) agglutination titres along with clinical improvement (P<0.01). SAT titres remained detectable in most cases for a longer period in spite of an effective antimicrobial therapy and clinical recovery. A substantial number of patients (84.2 %) presented with fever, this being the only complaint in 51.1 % of the cases. Complications were present in 8.8 % of the patients (arthritis excluded): this included the unusual complications of hydrocele (two cases), Stevens–Johnson syndrome (one case) and urinary tract infection (one case).Brucellaagglutinins were demonstrated in synovial, testicular, hydrocele and cerebrospinal fluids. There was no clinical suspicion of brucellosis in 439 cases (88.7 %) and the diagnosis was made only by routine serology. A two-drug regimen for 42–84 days with a follow-up 2ME test resulted in lower levels of relapse. These results suggest that, in endemic areas of the world, it should be mandatory to screen routinely for brucellosis due to protean clinical manifestations.
Streptococcus agalactiae Cβ protein gene (bac) sequence types, based on the repeated region of the cell-wall-spanning domain: relationship to virulence and a proposed standardized nomenclature
Authors: Kong Fanrong , Gidding Heather F. , Berner Reinhard , Gilbert Gwendolyn L.
Published: June 2006

The Cβprotein (Bac) ofStreptococcus agalactiae(group B streptococcus; GBS) is an IgA binding protein encoded bybac, of which at least 39 sequence types have been described, based on polymorphisms in the repeated region of the cell-wall-spanning domain (‘bacsequence types’). Cβis usually found in serotype Ib, less commonly in serotype II, and rarely in other serotypes. The aim of this study was to examine the prevalence, variety and distribution, among GBS serotypes and between invasive and superficial isolates, ofbacsequence types. A total of 1101 GBS isolates were tested, from 10 countries, with abac-specific PCR, and amplicons from all 255 (23 %) with positive results were sequenced. Ninety-seven percent (184/190) of serotype Ib and 37 % of serotype II isolates werebacpositive. The Cαprotein gene (bca) was present in 98 % (251/255), and insertion sequences IS1381and IS861in 94 % (239/255), ofbac-positive isolates. The authors identified 59bacsequence types belonging to 19 groups, based on length, from 496 to 946 bp, with up to six sequence variants (a–f) in each group. The medianbacsequence length of invasive isolates was significantly shorter than that of superficial isolates overall (640 versus 586 bp;P<0.001) and specifically for serotype Ib (541 versus 676 bp;P<0.001), and invasive isolates were significantly (P<0.001) more likely to have one or more 18 bp deletions relative to the original publishedbacsequence (X59771).bacsequence typing is a useful addition to the previously described genotyping system, and will help to predict relative virulence amongS. agalactiaeserotype Ib strains.
Antifungal effect of voriconazole on intracellular Candida glabrata, Candida krusei and Candida parapsilosis in human monocyte-derived macrophages
Authors: Bopp Lawrence H. , Baltch Aldona L. , Ritz William J. , Michelsen Phyllis B. , Smith Raymond P.
Published: June 2006

Infections caused byCandidaspecies other thanCandida albicansare increasingly common, and decreased susceptibility to azoles has made them more difficult to treat. Since phagocytic killing is important in elimination ofCandidainfections, intracellular killing of fluconazole-resistantCandida glabrata,Candida kruseiandCandida parapsilosis(four strains each) by voriconazole was investigated in human monocyte-derived macrophages (MDMs). MDMs were infected withCandida, and voriconazole was then added. MDMs were lysed at 0, 24 or 48 h after infection, and viableCandidain the lysates enumerated. Compared to the starting inoculum, the number of viable intracellularC. parapsilosisandC. glabratain untreated MDMs increased to 28 121 and 351 %, respectively, in 48 h. In contrast, the number ofC. kruseidecreased to 42 %. In MDMs treated with voriconazole, the decrease in viable count was dependent upon drug concentration. At 48 h,C. glabratawas killed only at 5× MIC (P<0.05),C. kruseiwas killed at all voriconazole concentrations, whileC. parapsilosiswas inhibited at 0.5 and 1× MIC and killed at ⩾2.5× MIC (P<0.05). The data show that intracellular growth and survival of theseCandidaspecies in the absence or presence of voriconazole vary markedly. The activity of voriconazole depends on the concentration of the drug and the time of exposure. For the 12Candidastrains studied, regression curves show that the maximum intracellular anticandidal activity of voriconazole was reached at 3.5–5× MIC.
Naturally occurring amino acids differentially influence the development of Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae
Authors: Al-Younes Hesham M. , Gussmann Joscha , Braun Peter R. , Brinkmann Volker , Meyer Thomas F.
Published: June 2006

The differential influence of individual amino acids on the growth of Chlamydia trachomatis versus Chlamydia (Chlamydophila) pneumoniae was investigated. Certain essential amino acids added in excess at the middle of the infection course resulted in varying degrees of abnormality in the development of the two species. If amino acids were added as early as 2 h post-infection, these effects were even more pronounced. The most effective amino acids in terms of C. trachomatis growth inhibition were leucine, isoleucine, methionine and phenylalanine. These amino acids elicited similar effects against C. pneumoniae, except methionine, which, surprisingly, showed a lower inhibitory activity. Tryptophan and valine marginally inhibited C. trachomatis growth and, paradoxically, led to a considerable enhancement of C. pneumoniae growth. On the other hand, some non-essential amino acids administered at the middle of or throughout the infection course differentially affected the development of the two species. For example, C. trachomatis growth was efficiently inhibited by glycine and serine, whereas C. pneumoniae was relatively less sensitive to these agents. Another difference was apparent for glutamate, glutamine and aspartate, which stimulated C. pneumoniae growth more than that of C. trachomatis. Overall, several distinctive patterns of susceptibility to excess amino acid levels were revealed for two representative C. trachomatis and C. pneumoniae isolates. Perturbation of amino acid levels, e.g. of leucine and isoleucine, might form a basis for the development of novel treatment or preventive regimens for chlamydial diseases.
Immunoproteomics of Actinobacillus actinomycetemcomitans outer-membrane proteins reveal a highly immunoreactive peptidoglycan-associated lipoprotein
Authors: Paul-Satyaseela Maneesh , Karched Maribasappa , Bian Zhao , Ihalin Riikka , Borén Thomas , Arnqvist Anna , Chen Casey , Asikainen Sirkka
Published: June 2006

In a search for novel bioactive cell surface structures of periodontal pathogens, it was found that sera from two patients withActinobacillus actinomycetemcomitans-associated infections reacted strongly at 17 kDa on immunoblots ofA. actinomycetemcomitansouter-membrane protein (OMP) preparations. The 17 kDa antigen was also recognized by anti-CsgA (Escherichia colicurli major subunit) antibody. The 17 kDaA. actinomycetemcomitansprotein was identified as peptidoglycan-associated lipoprotein (PAL; AaPAL) by two-dimensional immunoblotting and subsequent sequence analysis by mass spectrometry and bioinformatics tools. AaPAL was an OMP and a lipoprotein, and it had an OmpA-like domain. In a group of middle-aged subjects (n=26), serum reactivity to AaPAL was associated with the presence of periodontitis but not with the oral detection ofA. actinomycetemcomitans. Both human sera and rabbit antisera against three different types of antigens, the gel-purified AaPAL,A. actinomycetemcomitanswhole-cell antigens, and CsgA, recognized putative PALs of oral haemophili in addition to AaPAL. The results demonstrated that the novel AaPAL is a conserved bacterial lipoprotein. It is expressedin vivoand is strongly immunoreactive. The antigenic cross-reactivity found between AaPAL and oral haemophili may enhance local and systemic immuno-inflammatory reactions in periodontitis.
Acute peritonitis and salpingitis associated with streptococcal toxic shock syndrome caused by Lancefield group G α-haemolytic Streptococcus dysgalactiae subsp. equisimilis
Authors: Horii Toshinobu , Izumida Sayuri , Takeuchi Kiyotake , Tada Toyohiro , Ishikawa Jinko , Tsuboi Koji
Published: June 2006

The authors treated a patient for what appears to be the first reported occurrence of acute peritonitis and salpingitis associated with streptococcal toxic shock syndrome (STSS). This was caused by Lancefield group G α-haemolytic Streptococcus dysgalactiae subsp. equisimilis TKCH2004-001. The isolate showed M protein type stc36 and carried the spegg gene. To the best of the authors' knowledge, the present report represents the first case of STSS complicating acute peritonitis and salpingitis caused by Lancefield group G α-haemolytic S. dysgalactiae subsp. equisimilis.
Application of the resazurin microtitre assay for detection of multidrug resistance in Mycobacterium tuberculosis in Algiers
Authors: Nateche Farida , Martin Anandi , Baraka Saliha , Palomino Juan Carlos , Khaled Safia , Portaels Françoise
Published: June 2006

This study assessed the performance of a rapid, low-cost, colorimetric method, the resazurin microtitre assay (REMA) plate method, for the detection of resistance to isoniazid and rifampicin in 136 clinical isolates of Mycobacterium tuberculosis from two hospitals in Algiers. MICs were determined and the results were compared with those obtained with the conventional proportion method on Löwenstein–Jensen medium. Excellent results were obtained for the REMA plate method, with a sensitivity of 100 % for both isoniazid and rifampicin and a specificity of 98.3 and 99.2 %, respectively. The REMA plate method appears to be a reliable method for the rapid determination of multidrug-resistant tuberculosis and is a good alternative for use in resource-limited countries such as Algeria.
Nitrate reductase assay for detection of drug resistance in Mycobacterium tuberculosis: simple and inexpensive method for low-resource laboratories
Authors: Lemus Dihadenys , Montoro Ernesto , Echemendía Miguel , Martin Anandi , Portaels Françoise , Palomino Juan Carlos
Published: June 2006

The nitrate reductase assay (NRA) was used as an alternative method for detection of resistance to the first-line antituberculous drugs isoniazid, rifampicin, ethambutol and streptomycin. A total of 320 strains of Mycobacterium tuberculosis were studied and the results compared with the proportion method (PM) on Löwenstein–Jensen medium. The mean time to obtain results was 10 days and the overall agreement between the NRA and PM was 98.8 %. The NRA was easy to perform and represents a useful tool for rapid and accurate determination of drug-resistant M. tuberculosis strains in low-resource countries.
Close sequence comparisons are sufficient to identify human cis-regulatory elements
Authors: Prabhakar Shyam , Poulin Francis , Shoukry Malak , Afzal Veena , Rubin Edward M. , Couronne Olivier , Pennacchio Len A.
Published: June 2006

Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons. To address this problem, we identified evolutionarily conserved noncoding regions in primate, mammalian, and more distant comparisons using a uniform approach (Gumby) that facilitates unbiased assessment of the impact of evolutionary distance on predictive power. We benchmarked computational predictions against previously identified cis-regulatory elements at diverse genomic loci and also tested numerous extremely conserved human–rodent sequences for transcriptional enhancer activity using an in vivo enhancer assay in transgenic mice. Human regulatory elements were identified with acceptable sensitivity (53%–80%) and true-positive rate (27%–67%) by comparison with one to five other eutherian mammals or six other simian primates. More distant comparisons (marsupial, avian, amphibian, and fish) failed to identify many of the empirically defined functional noncoding elements. Our results highlight the practical utility of close sequence comparisons, and the loss of sensitivity entailed by more distant comparisons. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole-genome comparative analysis that explains most of the observations from empirical benchmarking. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for in vivo testing at embryonic time points.
Evidence for variation in abundance of antisense transcripts between multicellular animals but no relationship between antisense transcription and organismic complexity
Authors: Sun Miao , Hurst Laurence D. , Carmichael Gordon G. , Chen Jianjun
Published: June 2006

Given that humans have about the same number of genes as mice and not so many more than worm, what makes us more complex? Antisense transcripts are implicated in many aspects of gene regulation. Is there a functional connection between antisense transcription and organismic complexity, that is, is antisense regulation especially prevalent in humans? We used the same robust protocol to identify antisense transcripts in humans and five other metazoan genomes (mouse, rat, chicken, fruit fly, and nematode), and found that the estimated proportions of genes involved in antisense transcription are highly sensitive to the number of transcripts included in the analysis. By controlling for transcript abundance, we find that the probability that any given transcript is putatively involved in sense–antisense regulation is no higher in humans than in other vertebrates but appears unusually high in flies and especially low in nematodes. Similarly, there is no evidence that the proportion of sense–antisense transcripts is especially higher in humans than other vertebrates in a given subset of transcript sequences such as mRNAs, coding sequences, conserved, or nonconserved transcripts. Although antisense transcription might be enriched in mammalian brains compared with nonbrain tissues, it is no more enriched in human brain than in mouse brain. Overall, therefore, while we see striking variation between multicellular animals in the abundance of antisense transcripts, there is no evidence for a link between antisense transcription and organismic complexity. More particularly, we see no evidence that humans are in any way unusual among the vertebrates in this regard. Instead, our results suggest that antisense transcription might be prevalent in almost all metazoan genomes, nematodes being an unexplained exception.
Characterization of the Class IV Homeodomain-Leucine Zipper Gene Family in Arabidopsis
Authors: Nakamura Miyuki , Katsumata Hiroshi , Abe Mitsutomo , Yabe Naoto , Komeda Yoshibumi , Yamamoto Kotaro T. , Takahashi Taku
Published: June 2006

The Arabidopsis (Arabidopsis thaliana) genome contains 16 genes belonging to the class IV homeodomain-Leucine zipper gene family. These include GLABRA2, ANTHOCYANINLESS2, FWA, ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1), and PROTODERMAL FACTOR2 (PDF2). Our previous study revealed that atml1 pdf2 double mutants have severe defects in the shoot epidermal cell differentiation. Here, we have characterized additional members of this gene family, which we designated HOMEODOMAIN GLABROUS1 (HDG1) through HDG12. Analyses of transgenic Arabidopsis plants carrying the gene-specific promoter fused to the bacterial β-glucuronidase reporter gene revealed that some of the promoters have high activities in the epidermal layer of the shoot apical meristem and developing shoot organs, while others are temporarily active during reproductive organ development. Expression profiles of highly conserved paralogous gene pairs within the family were found to be not necessarily overlapping. Analyses of T-DNA insertion mutants of these HDG genes revealed that all mutants except hdg11 alleles exhibit no abnormal phenotypes. hdg11 mutants show excess branching of the trichome. This phenotype is enhanced in hdg11 hdg12 double mutants. Double mutants were constructed for other paralogous gene pairs and genes within the same subfamily. However, novel phenotypes were observed only for hdg3 atml1 and hdg3 pdf2 mutants that both exhibited defects in cotyledon development. These observations suggest that some of the class IV homeodomain-Leucine zipper members act redundantly with other members of the family during various aspects of cell differentiation. DNA-binding sites were determined for two of the family members using polymerase chain reaction-assisted DNA selection from random oligonucleotides with their recombinant proteins. The binding sites were found to be similar to those previously identified for ATML1 and PDF2, which correspond to the pseudopalindromic sequence 5′-GCATTAAATGC-3′ as the preferential binding site.
Feminism Spoken Here: Epistemologies for Interdisciplinary Development Research
Authors: Jackson Cecile
Published: June 2006

Development studies is a field characterized by an unusual degree of interdisciplinary and multidisciplinary research, and therefore is constantly subject both to pressures for the reproduction of disciplines as autonomous and self‐sufficient, and to an increasing steer from public funders of research for interdisciplinary work which is valued for its problem‐solving character and more apparent relevance, in an era greatly exercised by accountability. At a moment when the need to renew disciplinary interchange has intensified it is therefore instructive to consider the social relations which facilitate interdisciplinarity. This article does this through an argument that feminist cross‐disciplinary research shows how important shared values are to motivate and sustain these kinds of learning, and that an explicit focus on social justice as the core of development research can be the basis of such a renewal. If feminist interactions and solidarity provide the motivation, feminist epistemologies provide arguments for why socially engaged research is not ‘biased’, but stronger than research with narrower ideas of objectivity; why reflexivities and subjectivities are crucial to the conduct of research; and how these, and the convergence of concepts of individuals and persons favoured within different disciplines, might build the common ground required for greater disciplinary interchange.
Providence and Sympathy: Consoling the Bereaved in the Late Eighteenth Century
Authors: Richards Anna
Published: June 2006

In the Enlightenment period restrictions were imposed on mourning practices but grief was valued as a sign of natural humanity, as long as it remained moderate. Consolation was offered to the bereaved to help them temper excessive sadness. In the second half of the eighteenth century, influenced by the period's psychological thinking, the theory and the practice of consolation became more secular and more individualised than they had previously been; consolers took the demands of self‐interest and of the emotions into account to a greater extent. This meant an emphasis on the role of providence in the death of the loved one and on the need for sympathy. This article discusses the consequences and the challenges of these developments for consolatory texts. It suggests that they called for narrative strategies and concludes that the ‘Trostschrift’ and the sentimental novel began to occupy some of the same ground at this period.
Visions of the New World: Photography in Kafka's Der Verschollene
Authors: Duttlinger Carolin
Published: June 2006

Photography plays a central role in Franz Kafka's fictional travelogue Der Verschollene (1912–14), where it features as both explicit motif and implicit source material. Having never visited the United States, Kafka drew on genuine travel photographs as inspiration for his novel, assimilating them into his depiction of an imaginary America. While some scenes maintain the photographic stasis of their originals, others are animated to express the dynamism of modern life and the disorientation this can produce in the viewer's mind. Alongside such public travel photographs, however, Kafka also makes use of private pictures taken from his own family album. These traditional studio portraits act as models for the photographs featured within the plot, which illustrate the protagonist's continued attachment to his European origins. The latent sense of oppression inherent in these bourgeois portraits finds more brutal expression in the photographic source material which underlies the novel's unfinished conclusion. In the Oklahoma theatre episode photographic scenes of assassination and lynching invade the narrative, undermining its images of modernity and progress. In its diverse manifestations (both literal and intertextual) photography in Der Verschollene establishes a link between traditional and modern forms of visuality, thereby illustrating the circular, regressive character of the protagonist's journey.
The Author, The Novel, The Reader and The Perils of ‘Neue Lesbarkeit’: A Comparative Analysis of Bernhard Schlink's Selbs Justiz and Der Vorleser
Authors: Hall Katharina
Published: June 2006

Ten years after the publication of Der Vorleser, this article argues that Schlink's work can only be fully understood when viewed in the commercial contexts that currently shape both German and global literatures. By undertaking a comparative analysis of Schlink's debut detective novel, Selbs Justiz (1987) and his international best‐seller Der Vorleser (1995), the article explores the problematic tensions generated within these texts by the commercial demands of the literary market‐place, and, in a specifically German context, the influence of ‘neue Lesbarkeit’. Special consideration is given to the dynamic between Schlink's works and the reader/consumer, with particular emphasis on the impact of the popular literary codes within the texts. These are explored in conjunction with the reception theory of Wolfgang Iser and Umberto Eco, and through the lens of over two hundred reader responses. The article breaks new ground through its comparative approach, which traces the continuities or ‘narrative patterns’ in Schlink's detective writing and Der Vorleser for the first time. It also offers the first exploration of ‘general’, non‐academic reader responses to the works, allowing new insights into the texts’ operations and the tensions these create in relation to the novels’ treatment of the National Socialist past.
Transcription factors that regulate memory in humoral responses
Authors: Calame Kathryn
Published: June 2006

Summary:  At least three types of B lymphocytes are important for providing memory in a humoral immune response: ‘classical’ memory cells that do not secrete immunoglobulin (Ig), long‐lived plasma cells (LLPCs) in the bone marrow, and ‘innate‐like’ B‐1 cells. In this review, our work on B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1), a critical regulator of terminal B‐cell differentiation, is discussed in the context of current knowledge of all transcriptional controls that regulate these three types of B cells. Blimp‐1 is not required for formation of memory cells, but it is required for them to progress toward becoming plasma cells. Blimp‐1 is required for Ig secretion in plasma cells and in B‐1 cells. Induction of the activator X‐box‐binding protein‐1 and formation of µ‐secreted mRNA depend on Blimp‐1 in both cell types. Finally, even after their formation, LLPCs in the bone marrow continue to require Blimp‐1 for their maintenance.
The Tower of Babel of CD8+ T‐cell memory: known facts, deserted roads, muddy waters, and possible dead ends
Authors: Rocha Benedita , Tanchot Corinne
Published: June 2006

Summary:  Adequate antigen stimulation can lead to permanent modifications of primed cells and to the generation of memory T cells that have astonishingly improved capacities to deal with antigen. The overall properties of memory T cells (increased survival, precocious and increased division capacities, and improved effector functions) can be used to identify this unique cell type. However, each immune response may lead to the generation of multiple primed types that do not necessarily possess all these characteristics. It is not known whether these different cell types are just side products of the immune reaction or whether they are involved in disease control. Control of different infections may involve different challenges and lead to the generation of different types of immune reactions. Our major challenge is to unravel this complexity, but we must overcome our handicapped experimental tests and our imperfect a priori definitions.
Human virus‐specific CD8+ T cells: diversity specialists
Authors: Van Leeuwen Ester M. M. , De Bree Godelieve J. , Ten Berge Ineke J. M. , Van Lier René A. W.
Published: June 2006

Summary:  Human viruses elicit functionally highly diverse CD8+ T‐cell responses. This variation, which manifests in the memory or latency stage, includes differences in expansion requirements, migratory properties, homeostatic maintenance mechanisms, and constitutive effector properties, and it may reflect specific adaptations of the human immune system to challenges posed by individual pathogens. Longitudinal follow‐up of individuals after primary virus infections has revealed how divergent virus‐specific CD8+ T cells may develop from the initially expanded virus‐specific T‐cell effector pool. Recent findings have shown that CD8+ T cells reactive toward latent viruses may depend on other mechanisms for their homeostatic maintenance than T cells specific for cleared viruses. Whereas the latter can respond to the homeostatic cytokine interleukin‐7 (IL‐7), many persistent virus‐specific T cells, recognizing latent herpesviruses such as Epstein–Barr virus and cytomegalovirus (CMV), lack IL‐7 receptor α (IL‐7Rα) and depend on viral antigens to persist. Finally, CMV is unique in that it generates a vast pool of resting virus‐specific T cells with constitutive cytolytic effector function. The putative role of functionally diverse CD8+ T cells in protective immunity to persistent viruses is discussed in this review.
CD4+ memory T cells: functional differentiation and homeostasis
Authors: Stockinger Brigitta , Bourgeois Christine , Kassiotis George
Published: June 2006

Summary:  CD4+ T cells are central regulators of both humoral and cellular immune responses. There are many subsets of CD4+ T cells, the most prominent being T‐helper 1 (Th1), Th2, Th‐17, and regulatory T cells, specialized in regulating different aspects of immunity. Without participation by these CD4+ T‐cell subsets, B cells cannot undergo isotype switching to generate high‐affinity antibodies, the microbicidal activity of macrophages is reduced, the efficiency of CD8+ T‐cell responses and CD8+ T‐cell memory are compromised, and downregulation of effector responses is impaired. It therefore stands to reason that memory CD4+ T cells are likely to fulfill an important facilitator role in the maintenance and control of protective immune responses. This review discusses some issues of importance for the generation of memory CD4+ T cells and focuses in particular on their heterogeneity and plasticity, with respect to both phenotypic characteristics and function. Finally, we discuss a number of factors that affect long‐term maintenance of memory CD4+ T cells.
Signals required for programming effector and memory development by CD8+ T cells
Authors: Mescher Matthew F. , Curtsinger Julie M. , Agarwal Pujya , Casey Kerry A. , Gerner Michael , Hammerbeck Christopher D. , Popescu Flavia , Xiao Zhengguo
Published: June 2006

Summary:  Stimulation of naïve CD8+ T cells with antigen and costimulation results in proliferation and weak clonal expansion, but the cells fail to develop effector functions and are tolerant long term. Initiation of the program leading to the strong expansion and development of effector functions and memory requires a third signal that can be provided by interleukin‐12 (IL‐12) or interferon‐α (IFN‐α). CD4+ T cells condition dendritic cells (DCs) to effectively present antigen to CD8+ T cells, and this conditioning involves, at least in part, CD40‐dependent upregulation of the production of these signal 3 cytokines by the DCs. Upon being fully activated, the cytotoxic T lymphocytes develop activation‐induced non‐responsiveness (AINR), a form of split anergy characterized by an inability to produce IL‐2 to support continued expansion. If antigen remains present, IL‐2 provided by CD4+ T cells can reverse AINR to allow further expansion of the effector population and conversion to responsive memory cells following antigen clearance. If IL‐2 or potentially other proliferative signals are not available, persistent antigen holds cells in the AINR state and prevents the development of a responsive memory population. Thus, in addition to antigen and costimulation, CD8+ T cells require cytokine signals at distinct stages of the response to be programmed for optimal generation of effector and memory populations.
T‐cell memory and recall responses to respiratory virus infections
Authors: Hikono Hirokazu , Kohlmeier Jacob E. , Ely Kenneth H. , Scott Iain , Roberts Alan D. , Blackman Marcia A. , Woodland David L.
Published: June 2006

Summary:  The respiratory tract is characterized by its large surface area and the close association of an extensive vasculature with the external environment. As such, the respiratory tract is a major portal of entry for many pathogens. The immune system is able to effectively control most pulmonary pathogens and establish immunological memory that is capable of mediating an accelerated and enhanced recall response to secondary pathogen challenge. A key component of the recall response in the lung involves the rapid response of antigen‐specific memory CD8+ T cells. Recent studies have shown that memory CD8+ T cells are extremely heterogeneous in terms of phenotype, function, anatomical distribution, and longevity. However, we have little understanding of how the different subsets of memory cells actually contribute to the recall response, especially with respect to peripheral or mucosal sites, such as the lung. Since immunological memory is the cornerstone of vaccination, it is essential that we understand how different memory CD8+ T‐cell subsets are initially generated, maintained over time, and contribute to recall responses. This review focuses on memory T cells that mediate recall responses to influenza and parainfluenza virus infections in the lung.
Establishment and recall of CD8+ T‐cell memory in a model of localized transient infection
Authors: Kedzierska Katherine , La Gruta Nicole L. , Turner Stephen J. , Doherty Peter C.
Published: June 2006

Summary:  The influenza A virus model of localized, transient respiratory infection provides a well‐defined experimental system for dissecting the induction and maintenance of CD8+ T‐cell memory. This review focuses on quantitative and qualitative aspects of the prominent DbNP366‐ and DbPA224‐specific CD8+ T‐cell responses in virus‐infected B6 mice. The different virus‐specific effector and memory sets are compared by phenotypic [CD62L, interleukin‐7 receptor‐α (IL‐7Rα), and IL‐15Rβ expression] and functional [interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), and IL‐2 production] analyses. Most clonotypes [defined by T‐cell receptor (TCR) CDR3β sequence] generated during the acute phase of infection survive into memory, with those expressing the more consensus ‘canonical’ TCRs being the major contributors to the recall response. The extent of clonal expansion and the size of memory CD8+ T‐cell populations has been characterized for mice challenged with either wildtype or mutant viruses, where broadly equivalent DbNP366 and DbPA224 expression was achieved by disabling the peptides in their native configuration, then expressing them in the viral neuraminidase protein. Combining the clonotypic and antigen dose analyses led to a somewhat mechanistic conclusion that the magnitude of any virus‐specific CD8+ T‐cell response will be a direct function of antigen dose and the size of the naïve or memory CD8+ T‐cell precursor pool.
Control of CD4+ T‐cell memory by cytokines and costimulators
Authors: Dooms Hans , Abbas Abul K.
Published: June 2006

Summary:  During T‐cell priming, cytokines and costimulatory molecules provide important signals that determine the magnitude and quality of the response. Although the functions of defined cytokines and costimulators in the primary T‐cell response are well characterized, much less is known about how these factors contribute to memory T‐cell development and survival. Since memory cells are thought to be long‐lived progeny of the primary response, it is conceivable that the same signals shaping initial T‐cell expansion and differentiation also contribute to memory generation. Here, we review evidence and show novel data on the role of the cytokines interleukin‐2 (IL‐2) and IL‐7 and the costimulator CD28 in CD4+ memory T‐cell development. We emphasize that transient IL‐2 and CD28 signals during priming imprint a long‐lasting survival advantage in primed T cells, thus contributing to the persistence of a memory population. The requirement for IL‐2 and CD28 signals is not linked to promoting T‐cell division and expansion but most likely due to their capacity to (i) promote effector cell differentiation; (ii) induce survival proteins, and, as we discuss in more detail; (iii) program expression of receptors for ‘memory survival factors’ such as IL‐7. Studies exploring the therapeutic potential of these insights are also discussed.
Developing and maintaining protective CD8+ memory T cells
Authors: Williams Matthew A. , Holmes Brittany J. , Sun Joseph C. , Bevan Michael J.
Published: June 2006

Summary:  A critical aim of vaccine‐related research is to identify the mechanisms by which memory T cells are formed and maintained over long periods of time. In recent years, we have designed experiments aimed at addressing two key questions: (i) what are the factors that maintain functionally responsive CD8+ memory cells over long periods of time, and (ii) what are the signals during the early stages of infection that drive the differentiation of long‐lived CD8+ memory T cells? We have identified a role for CD4+ T cells in the generation of CD8+ T‐cell‐mediated protection from secondary challenge. While CD4+ T cells appear to play a role in the programme of CD8 memory, we find that they are also required for the long‐term maintenance of CD8+ memory T‐cell numbers and function. This property is independent of CD40–CD40L interactions, and we propose a role for CD4+ T cells in maintaining the ability of CD8+ memory T cells to respond to interleukin‐7 (IL‐7) and IL‐15. By manipulating both the time course of infection and the timing of antigen presentation to newly recruited CD8+ T cells, we also demonstrate that the programming of effector and memory potential are at least partially distinct processes.
The rationale for the IL‐2‐independent generation of the self‐renewing central memory CD8+ T cells
Authors: Fearon Douglas T. , Carr James M. , Telaranta Aino , Carrasco Marlene J. , Thaventhiran James E. D.
Published: June 2006

Summary:  Clones of CD8+ T cells that have been selected in the primary response must have a mechanism by which they can continuously or intermittently generate new effector cells. Several years ago, this mechanism was proposed to involve a self‐renewing, stem cell‐like subset that could avoid the differentiating effects of interleukin‐2 (IL‐2). The model considered the stem cell subset to be contained within the central memory population of CD8+ T cells (TCM). This proposal was inconsistent with subsequent findings suggesting that all antigen‐activated CD8+ T cells differentiated to effector cells (TEFF) during the primary response and that TCM developed during the memory phase by de‐differentiating from effector memory cells (TEM). However, findings have since been reported that support the stem cell model. First, studies indicate that TEM do not serve as the precursors of TCM. Second, transcriptional repressors of IL‐2 signaling do enhance the memory response. Third, memory cells lacking effector functions and with a capacity to replicate in a secondary response develop in the absence of signaling through the IL‐2/IL‐15 receptor. Taken together, these findings suggest that antigen‐activated CD8+ T cells with a stem cell‐like capability for maintaining proliferative potential develop by an unknown IL‐2‐independent process. The challenge is now to identify this unknown pathway of clonal expansion.
Immunity and immunological memory following smallpox vaccination
Authors: Amanna Ian J. , Slifka Mark K. , Crotty Shane
Published: June 2006

Summary:  The smallpox vaccine consists of live vaccinia virus and is generally considered the gold standard of vaccines, since it is the only one that has led to the complete eradication of an infectious disease from the human population. Renewed fears that smallpox might be deliberately released in an act of bioterrorism have led to resurgence in the study of immunity and immunological memory to vaccinia virus and other poxviruses. Here we review our current understanding of memory T‐cell, memory B‐cell, and antibody responses to vaccinia and related poxviruses, both in animal models and human subjects. Of particular interest are recent advances in understanding protective immunity to poxviruses, quantifying immunological memory to the smallpox vaccine in humans, and identifying major vaccinia‐specific T‐cell and B‐cell epitopes. In addition, potential mechanisms for maintenance of immunological memory are discussed.
Memory of mice and men: CD8+ T‐cell cross‐reactivity and heterologous immunity
Authors: Selin Liisa K. , Brehm Michael A. , Naumov Yuri N. , Cornberg Markus , Kim Sung‐Kwon , Clute Shalyn C. , Welsh Raymond M.
Published: June 2006

Summary:  The main functions of memory T cells are to provide protection upon re‐exposure to a pathogen and to prevent the re‐emergence of low‐grade persistent pathogens. Memory T cells achieve these functions through their high frequency and elevated activation state, which lead to rapid responses upon antigenic challenge. The significance and characteristics of memory CD8+ T cells in viral infections have been studied extensively. In many of these studies of T‐cell memory, experimental viral immunologists go to great lengths to assure that their animal colonies are free of endogenous pathogens in order to design reproducible experiments. These experimental results are then thought to provide the basis for our understanding of human immune responses to viruses. Although these findings can be enlightening, humans are not immunologically naïve, and they often have memory T‐cell populations that can cross‐react with and respond to a new infectious agent or cross‐react with allo‐antigens and influence the success of tissue transplantation. These cross‐reactive T cells can become activated and modulate the immune response and outcome of subsequent heterologous infections, a phenomenon we have termed heterologous immunity. These large memory populations are also accommodated into a finite immune system, requiring that the host makes room for each new population of memory cell. It appears that memory cells are part of a continually evolving interactive network, where with each new infection there is an alteration in the frequencies, distributions, and activities of memory cells generated in response to previous infections and allo‐antigens.