bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigenic Variation in Pneumocystis1
Authors: STRINGER JAMES R.
Published: December 2006

ABSTRACT. Pneumocystis is a genus containing many species of non‐culturable fungi, each of which infects a different mammalian host. Pneumonia caused by Pneumocystis is a problem in immunodeficient humans, but not in normal humans. Nevertheless, it appears that Pneumocystis organisms cannot survive and proliferate outside of their mammalian hosts, suggesting that Pneumocystis parasitizes immunocompetent mammals. Residence in immunocompetent hosts may rely on camouflage perpetrated by antigenic variation. In P. carinii, which is found in rats, there exist three families of genes that appear to be designed to create antigenic variation. One gene family, which encodes the major surface glycoprotein (MSG), contains nearly 100 members. Expression of the MSG family is controlled by restricting transcription to the one gene that is linked to a unique expression site. Changes in the sequence of the MSG gene linked to the expression site occur and appear to be caused by recombination with MSG genes not at the expression site. Preliminary evidence suggests that gene conversion is the predominant recombination mechanism.
From Silent Genes to Noisy Populations—Dialogue Between the Genotype and Phenotypes of Antigenic Variation1
Authors: MARCELLO LUCIO , BARRY J. DAVID
Published: December 2006

ABSTRACT.African trypanosomes evade humoral immunity through antigenic variation whereby, they switch expression of the variant surface glycoprotein (VSG)gene encoding their glycoprotein surface coat. Switching proceeds by duplication from an archive of silentVSGgenes into a transcriptionally active locus, and precedent suggests silent genes can contribute, combinatorially to formation of expressed, functional genes through segmental gene conversion. The genome project has revealed that most of the silent archive consists of hundreds ofVSGgenes in subtelomeric tandem arrays, and that most of these are not functional genes. The aim of this review is to explore links between the uncovered trypanosome genotype and the phenotype of antigenic variation, stretching from the broad phenotype—transmission in the field and the overcoming of herd immunity—to events within single infections. Highlighting in particular the possible impact of phenotype selection on the evolution of theVSGarchive and the mechanisms for its expression leads to a theoretical framework to further our understanding of this complex immune evasion strategy.
African Trypanosomes: Intracellular Trafficking of Host Defense Molecules1
Authors: SHIFLETT APRIL M. , FAULKNER SARA D. , COTLIN LAURA F. , WIDENER JUSTIN , STEPHENS NATALIE , HAJDUK STEPHEN L.
Published: December 2006

ABSTRACT. Trypanosoma brucei brucei is the causative agent of Nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. A minor subfraction of human high‐density lipoprotein (HDL), containing apolipoprotein A‐I (APOA1), apolipoprotein L‐I (APOL1) and haptoglobin‐related protein (HPR) provides this innate protection against T. b. brucei infection. Both HPR and APOL1 are cytotoxic to T. b. brucei but their specific activities for killing increase several hundred‐fold when assembled in the same HDL. This HDL is called trypanosome lytic factor (TLF) and kills T. b. brucei following receptor binding, endocytosis, and lysosomal localization. Trypanosome lytic factor is activated in the acidic lysosome and facilitates lysosomal membrane disruption. Lysosomal localization is necessary for T. b. brucei killing by TLF. Trypanosoma brucei rhodesiense, which is indistinguishable from T. b. brucei, is resistant to TLF killing and causes human African sleeping sickness. Human infectivity by T. b. rhodesiense correlates with the evolution of a human serum resistance associated protein (SRA) that is able to ablate TLF killing. When T. b. brucei is transfected with the SRA gene it becomes highly resistant to TLF and human serum. In the SRA transfected cells, intracellular trafficking of TLF is altered and TLF mainly localizes to a subset of SRA containing cytoplasmic vesicles but not to the lysosome. These findings indicate that the cellular distribution of TLF is influenced by SRA expression and may directly determine susceptibility.
The Toxoplasma gondii Parasitophorous Vacuole Membrane: Transactions Across the Border1
Authors: MARTIN ANGELA M. , LIU TING , LYNN BERT C. , SINAI ANTHONY P.
Published: December 2006

ABSTRACT. The obligate intracellular protozoan Toxoplasma gondii establishes its replication permissive niche within the infected host cell. This niche, the parasitophorous vacuole (PV), is delimited from the host cell cytoplasm by the PV membrane (PVM). In this chapter we highlight the roles of the PVM in the remodeling of host cell architecture, nutrient acquisition, the manipulation of signaling, and touch upon the potential roles in the parasite developmental cycle. We further present the PVM as a unique and dynamic “organelle” found only within the infected cell where it is established outside the parent organism. Despite its importance little is known about the biology of the PVM. There has, however, been a recent renewal of interest in the PVM, the study of which has become more tractable with the application of both classical approaches as well as genomic and proteomic analyses. In this review we discuss the diverse activities associated with the PVM and present pressing questions that remain to be elucidated regarding this enigmatic organelle.
Structure, Thermal Behavior, Chemical Durability, and Optical Properties of the Na2O–Al2O3–TiO2–Nb2O5–P2O5 Glass System
Authors: Teixeira Zaine , Alves Oswaldo Luiz , Mazali Italo Odone
Published: December 2006

The FTIR, Raman, UV‐Vis, 31P MAS‐NMR, DTA, and refractive index measurements have been combined to investigate a series of glasses with the general formula 20Na2O–5Al2O3−xTiO2–(45−x)Nb2O5–30P2O5, 15≤x≤45. The glass structure, as well as thermal, optical, and chemical durability properties, were then described as functions of the fNb/fTi ratio. An increase of the fNb/fTi ratio correlates with a decrease in length of the average phosphate chains linked through Nb–O–P and Ti–O–P bonds, with an increase in the glass stability and with increase in the linear refractive indices at 632.8 nm from 1.79 to 1.89. Furthermore, niobium is more effective than titanium in improving chemical durability.
Large‐Scale Hydrothermal Synthesis of Twinned Rutile Titania
Authors: He Ming , Yu Lei , Lu Xiaohua , Feng Xin
Published: December 2006

The dispersed, regular twinned rutile titania (TiO2) has been firstly generated by the hydrothermal treatment of potassium hexatitanate whiskers in 1M HCl solution by rearranging structural units. It has been proved that the original structures of starting materials have a tremendous influence on the nucleation process, the crystal growth, and the morphology during the hydrothermal process.
Value of DNA Evidence in Detecting Crime
Authors: Bond John W.
Published: December 2006

ABSTRACT: DNA material is now collected routinely from crime scenes for a wide range of offences and the timely processing of the DNA is seen as key to its success in investigating and detecting crime. An analysis of DNA material recovered from the volume crime offences of residential burglary, commercial burglary, and theft of motor vehicle in Northamptonshire, U.K., in 2004 has enabled the DNA to be categorized into seven sources. Further analysis using a logistical regression has revealed a number of predictors, other than timeliness, that greatly influence whether the DNA material recovered from a crime scene enables the crime to be detected. The results indicate that a number of these predictors are of statistical significance and may be just as relevant in determining whether DNA successfully detects the crime as the timeliness of the processing of the DNA material. The most significant predictor was found to be investigating officer accreditation with location, quantity, and type of DNA material at the crime scene also being relevant. Accreditation of the Crime Scene Examiner recovering the DNA material was found not to be significant. Consideration is given to where further emphasis is needed by the U.K. police service to maximize the opportunities to detect volume crime with DNA.
Variation in Nuclear DNA Concentrations During Urination*
Authors: Johnson Donald J. , Calderaro Alexa C. , Roberts Katherine A.
Published: December 2006

ABSTRACT: This study examined the cellular origin and concentration of nuclear DNA in human urine. Ten subjects provided two entire, first‐morning voids: one as a single specimen and one as a consecutive series of samples. The serial samples were centrifuged, organically extracted, and quantified by slot‐blot analysis. Total DNA concentrations ranged from 0.02 to 21.3 ng/mL for the males and 25.0 to 96.9 ng/mL for the females. The female samples were found to contain numerous vaginal epithelial cells. DNA was detected in all of the serial samples of nine subjects; however, the DNA concentrations varied considerably. With six subjects, the DNA concentration of the first serial sample was at least three times greater than that of the entire void. DNA was only detected in the first 21% of the void from one male subject. The results of this study have implications for the collection of urine samples.
Evaluation of the Suchey–Brooks Method for Aging Skeletons in the Balkans
Authors: Djurić Marija , Djonić Danijela , Nikolić Slobodan , Popović Djordje , Marinković Jelena
Published: December 2006

ABSTRACT: This study has been carried out to examine whether the Suchey–Brooks (S&B) methods could be successfully applied in age assessment of populations from the Balkans. The known‐age sample consists of 33 females and 52 males pairs of pubic bones collected from the autopsy cases. Age estimation by S&B method showed an accuracy of 89.74% in males and 72.0% in females. Statistical analysis showed a positive correlation between the actual age of the investigated individuals and age phases obtained by the S&B method, although the mean values of the sixth age category differed significantly compared with the original model. The most reliable indicators in both sexes were the relief of the symphyseal surface, lipping, symphyseal rim, and dorsal margin. The discriminating power of these indicators was the least reliable in distinguishing S&B phases 2 and 3. Based on these results, the appropriate recommendations for aging Serbian populations are made. There was a good agreement between two observers (κ=0.726).
Allele Frequencies for Two Short Tandem Repeat Loci in the Chinese Han Population from Chengdu, China, and a Thai Population from Thailand
Authors: Wang Yanyun , Wang Zhuo , Zhou Bin , Du Bin , Zhang Beilei , Zhang Gengqian , Jia Yi , Wei Yesheng , Zhang Lin
Published: December 2006

POPULATION: Chinese Han and Thai.
STR Data for the AmpFlSTR® Identifiler® Loci from the Three Main Ethnic Indigenous Population Groups (Iban, Bidayuh, and Melanau) in Sarawak, Malaysia
Authors: Suadi Zaliha , Siew Lau Cheng , Tie Rita , Hui Wee Boon , Asam Anil , Thiew Sim Hang , Boon Lim Kong
Published: December 2006

POPULATION: Iban (n=195), Bidayuh (n=195), Melanau (n=128).
The Green Revolution, development of labor markets, and poverty reduction in the rural Philippines, 1985–2004
Authors: Estudillo Jonna P. , Sawada Yasuyuki , Otsuka Keijiro
Published: December 2006

Using a long‐term household panel data set collected in three rural villages in the Philippines in 1985 and 2004, this article explores how the Green Revolution and development of the labor markets have affected household income and poverty situation. The initial rise in income associated with the Green Revolution and a stronger credit access has enabled the households to allocate funds for investing in children's schooling. With the increased integration of the rural with the urban labor market, these children are able to explore labor opportunities in the nonfarm sector that resulted in a decline in poverty by about one‐half. The landless households, who are less educated, benefited, too, from the expansion of the nonfarm labor market, because of the rise in rural wages associated with the rise in demand for the unskilled labor, which is by far their most important asset.
Rural income dynamics and poverty reduction in Thai villages from 1987 to 2004
Authors: Cherdchuchai Supattra , Otsuka Keijiro
Published: December 2006

This article aims to examine the factors contributing to the increase in household income and the corresponding reduction in poverty in rural Thai villages from 1987 to 2004 by employing household panel data. It is found that there has been a significant structural shift of household income away from farm to nonfarm income sources, as well as a reduction in the income gap and the difference in poverty incidence between favorable and unfavorable regions. Such decreases in poverty and its regional gap have been associated with the declining importance of income accrued to farm land, measured by farm size and the availability of irrigation, and with the increasing importance of human capital, measured by the proportion of working members who have graduated from post lower secondary schools. Such findings indicate that the success in rural poverty reduction in Thailand has resulted from the development of the rural nonfarm sector coupled with the improvement of the schooling levels of the rural population.
Income dynamics and pathways out of rural poverty in Bangladesh, 1988–2004
Authors: Nargis Nigar , Hossain Mahabub
Published: December 2006

Bangladesh has made considerable progress in alleviating poverty in the recent past. Using data from a nationally representative longitudinal survey of rural households in Bangladesh conducted in three waves in 1988, 2000, and 2004, this article relates the dynamics of rural poverty reduction to the structural shift in income generation mechanism from farm to nonfarm activities, changing household factor endowments, and the adoption of improved agricultural technologies over time.1 The findings show that the occupational shift from the farm to the nonfarm sector, such as trade, business, and services, as well as the expansion of cultivated areas through tenancy, enhance income growth. Geographic mobility, overseas migration in particular, makes a significant contribution to income growth as well. The reduction in poverty appears to be vitally dependent on the enhancement of the endowment of human and physical capital that augments the poor households' capability to better exploit income‐generating opportunities and place the households on a sustainable route out of poverty.
The role of local nonfarm activities and migration in reducing poverty: evidence from Ethiopia, Kenya, and Uganda
Authors: Matsumoto Tomoya , Kijima Yoko , Yamano Takashi
Published: December 2006

By using cross‐sectional data from Ethiopia, Kenya, and Uganda, this article estimates the determinants of the participation in local nonfarm activities and migration at the individual level and then estimates the determinants of farm and nonfarm income. The results indicate that schooling and local language ability increase participation in local nonfarm activities and migration. Schooling also is found to increase nonfarm income at the household level but not farm income. We also find that farm household members from low‐potential agricultural areas are more likely to participate in local nonfarm activities and migration than those from high‐potential agricultural areas. Thus, the results suggest that local nonfarm activities and migration offer employment opportunities for workers from low‐potential agricultural areas. Indeed, the nonfarm activities and migration is likely to provide an important pathway to reduce poverty in low‐potential agricultural areas in East Africa.
Poverty and the rural nonfarm economy in Oromia, Ethiopia
Authors: Van Den Berg Marrit , Kumbi Girma Earo
Published: December 2006

The rural nonfarm sector has gained increasing importance not only in Asia but also in Africa. It is, however, widely believed that in most parts of Africa, the growth of the nonfarm economy has increased inequality and has had a limited effect on the poor, who face entry barriers to nonfarm activities. The present article analyzes the relation between nonfarm income, poverty, and inequality in Oromia, Ethiopia. We use two complementary methodologies: (i) econometric estimates of household income from the nonfarm sector; and (ii) a Gini decomposition of analysis income inequality by source. The results consistently indicate that in Oromia entry barriers to nonfarm activities is low, and the general growth of the sector will benefit the poor.
Frequency, function and CLA expression of CD4+CD25+FOXP3+ regulatory T cells in bullous pemphigoid
Authors: Rensing‐Ehl Anne , Gaus Barbara , Bruckner‐Tuderman Leena , Martin Stefan F.
Published: December 2006

Abstract:  Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies to collagen XVII and tissue‐separation along the dermo‐epidermal junction. We addressed the question whether the loss of tolerance in BP patients is associated with a reduction and/or functional impairment of CD4+CD25+FOXP3+ regulatory T cells, which are essential for the active maintenance of self tolerance. The relative and absolute frequency of CD4+CD25+ and CD4+CD25high regulatory T cells in the peripheral blood of newly diagnosed, untreated patients was similar to that of healthy controls. Interestingly, more than 50% of circulating CD4+CD25high regulatory T cells from both patients as well as healthy controls expressed cutaneous lymphocyte‐associated antigen. Considerable numbers of FOXP3+ cells were detected in lesional skin of patients. CD4+CD25+ regulatory T cells of patients were functionally intact as assessed by their ability to suppress allogeneic as well as antigen‐specific T‐cell proliferation. These data argue against a general defect of CD4+CD25+FOXP3+ regulatory T cells in patients with BP.
Negative‐pressure wound therapy: a snapshot of the evidence
Authors: Mendonca Derick A , Papini Remo , Price Patricia E
Published: December 2006

Topical negative pressure (TNP) is a mode of therapy used to encourage wound healing. It can be used as a primary treatment for chronic/complex wounds or as an adjunct to surgery. Based on the evidence to date, the clinical effectiveness of negative‐pressure therapy is still unclear. Although case reports and retrospective studies have demonstrated enhanced wound healing in acute/traumatic wounds, chronic wounds, infected wounds, wounds secondary to diabetes mellitus, sternal wounds and lower limb wounds, there are very few randomised controlled trials, with unclear results. The evidence is lacking for the use of TNP therapy for other indications to enhance wound healing such as patients with decubitus ulcers, diabetes and peripheral vascular disease and to improve skin graft take. There have been, as yet, no quality‐of‐life studies available for negative‐pressure therapy. Despite this, the usage of TNP has increased. This review provides an overview of clinical studies using TNP and proposes avenues for further research to elucidate the exact mechanism of TNP, in addition to large randomised controlled clinical trials of patients undergoing this therapy.
In vitro diffusion bed, 3‐day repeat challenge ‘capacity’ test for antimicrobial wound dressings
Authors: Greenman John , Thorn Robin MS , Saad Saliah , Austin Andrew J
Published: December 2006

The aim of this study was to develop an in vitro wound infection model that allows the comparison of the bacterial kill rate of antimicrobial wound dressings over the course of 3 days, with renewed microbial challenges each day, under realistic wound‐like conditions. A test bed model of a moderately exuding wound was constructed from a hydrogel containing releasable foetal calf serum (FCS), and cellulose discs dosed with test microbes (Methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa) suspended in 50% FCS applied at the interface between the test dressing and the hydrogel test bed. Freshly prepared discs were used to challenge the same dressing over a 23‐hour period for a course of 3 days. Different test dressings produced differing kill rates, allowing quantitative comparison of both their immediate activity and their capacity to continue working over 3 days, within a fluid‐donating system similar to the situation in vivo. The reported method has significant advantages over established test procedures since it enables the researcher to assess the antimicrobial capacity of wound dressings to continue working under conditions that match those encountered in wounds. These key conditions are those that would be expected to impede the action of the dressing and protect the infecting organisms.
Choices and constraints: individual perceptions of the voluntary redundancy experience
Authors: Clarke Marilyn
Published: December 2006

This article considers how voluntary redundancy influences individual perceptions of retrenchment. Semi‐structured interviews were conducted with people who had taken voluntary redundancy from a range of Australian public and private sector organisations. The article argues that, although some employees may feel pressured into accepting voluntary redundancy, for most people it provides a better alternative to involuntary retrenchment, enabling them to maintain self‐esteem and reducing the negative psychological, physical and financial impacts normally associated with retrenchment. However, it also suggests that redundancy programmes need to be managed strategically to avoid creating a ‘package culture’ mentality in which turnover becomes contingent on receiving a redundancy package.
The generation of nondiffracting beams using inexpensive computer-generated holograms
Authors: López-Mariscal Carlos , Gutiérrez-Vega Julio C.
Published: December 2006

We present a simple experimental procedure for producing a computer-generated hologram of good quality. As an example, the transverse intensity and phase structure of nondiffracting beams is investigated.
The polarization of skylight: An example from nature
Authors: Smith Glenn S.
Published: December 2006

A simple analytical model is presented for calculating the major features of the polarization of skylight over a hemisphere centered on an earthbound observer. The model brings together material from different topics in optics: polarization of plane waves, natural (unpolarized) light, and dipole scattering. Results calculated with the simple model are compared with experimental data. A brief description of the ability of insects to sense the polarization of skylight and their use of it for navigation is given.
Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes
Authors: Wencker Mélanie , Sausse Céline , Derse David , Gazzolo Louis , Duc Dodon Madeleine
Published: December 2006

The human pre-T-cell receptor alpha (TCRα; pTα) gene encodes a polypeptide which associates with the TCRβ chain and CD3 molecules to form the pre-TCR complex. The surface expression of the pre-TCR is pTα dependent, and signaling through this complex triggers an early αβ T-cell developmental checkpoint inside the thymus, known as β-selection. E2A transcription factors, which are involved at multiple stages of T-cell development, regulate the transcription of the pTα gene. Here we show that the regulatory protein Tax of the human T-cell leukemia virus type 1 (HTLV-1) efficiently suppresses the E47-mediated activation of the pTα promoter. Furthermore, we report that in Tax lentivirally transduced human MOLT-4 T cells, which constitutively express the pTα gene, the amount of pTα transcripts decreases. Such a decrease is not observed in MOLT-4 cells transduced by a vector encoding the Tax mutant K88A, which is unable to interact with p300. These data underline that Tax inhibits pTα transcription by recruiting this coactivator. Finally, we show that the expression of Tax in human immature thymocytes results in a decrease of pTα gene transcription but does not modify the level of E47 transcripts. These observations indicate that Tax, by silencing E proteins, down-regulates pTα gene transcription during early thymocyte development. They further provide evidence that Tax can interfere with an important checkpoint during T-cell differentiation in the thymus.
Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes
Authors: Ciccaglione Anna R. , Stellacci Emilia , Marcantonio Cinzia , Muto Valentina , Equestre Michele , Marsili Giulia , Rapicetta Maria , Battistini Angela
Published: December 2006

Hepatitis C virus (HCV) proteins are known to interfere at several levels with both innate and adaptive responses of the host. A key target in these effects is the interferon (IFN) signaling pathway. While the effects of nonstructural proteins are well established, the role of structural proteins remains controversial. We investigated the effect of HCV structural proteins on the expression of interferon regulatory factor 1 (IRF-1), a secondary transcription factor of the IFN system responsible for inducing several key antiviral and immunomodulatory genes. We found substantial inhibition of IRF-1 expression in cells expressing the entire HCV replicon. Suppression of IRF-1 synthesis was mainly mediated by the core structural protein and occurred at the transcriptional level. The core protein in turn exerted a transcriptional repression of several interferon-stimulated genes, targets of IRF-1, including interleukin-15 (IL-15), IL-12, and low-molecular-mass polypeptide 2. These data recapitulate in a unifying mechanism, i.e., repression of IRF-1 expression, many previously described pathogenetic effects of HCV core protein and suggest that HCV core-induced IRF-1 repression may play a pivotal role in establishing persistent infection by dampening an effective immune response.
Epstein-Barr Virus-Induced Resistance to Drugs That Activate the Mitotic Spindle Assembly Checkpoint in Burkitt's Lymphoma Cells
Authors: Leao Maria , Anderton Emma , Wade Mark , Meekings Kiran , Allday Martin J.
Published: December 2006

Epstein-Barr virus (EBV) is associated with a number of human cancers, and latent EBV gene expression has been reported to interfere with cell cycle checkpoints and cell death pathways. Here we show that latent EBV can compromise the mitotic spindle assembly checkpoint and rescue Burkitt's lymphoma (BL)-derived cells from caspase-dependent cell death initiated in aberrant mitosis. This leads to unscheduled mitotic progression, resulting in polyploidy and multi- and/or micronucleation. The EBV latent genes responsible for this phenotype are expressed from the P3HR1 strain of virus and several viruses with similar genomic deletions that remove the EBNA2 gene. Although EBNA2 and the latent membrane proteins are not expressed, the EBNA3 proteins are present in these BL cells. Survival of the EBV-positive cells is not consistently associated with EBV lytic gene expression or with the genes that are expressed in EBV latency I BL cells (i.e., EBNA1, EBERs, and BARTs) but correlates with reduced expression of the cellular proapoptotic BH3-only protein Bim. These data suggest that a subset of latent EBV gene products may increase the likelihood of damaged DNA being inherited because of the impaired checkpoint and enhanced survival capacity. This could lead to greater genetic diversity in progeny cells and contribute to tumorigenesis. Furthermore, since it appears that this restricted latent EBV expression interferes with the responses of Burkitt's lymphoma-derived cells to cytotoxic drugs, the results of this study may have important therapeutic implications in the treatment of some BL.
Rapid Memory CD8+T-Lymphocyte Induction through Priming with RecombinantMycobacterium smegmatis
Authors: Hovav Avi-Hai , Cayabyab Mark J. , Panas Michael W. , Santra Sampa , Greenland John , Geiben Ralf , Haynes Barton F. , Jacobs William R. , Letvin Norman L.
Published: December 2006

The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinantMycobacterium smegmatisstrain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4+T lymphocytes with a functional profile of helper cells as well as a CD8+T-lymphocyte population. These CD8+T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant-mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+T lymphocytes. This work demonstrates a remarkable skewing of recombinant-mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8+T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.
Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection
Authors: Wagoner Jessica , Austin Michael , Green Jamison , Imaizumi Tadaatsu , Casola Antonella , Brasier Allan , Khabar Khalid S. A. , Wakita Takaji , Gale Michael , Polyak Stephen J.
Published: December 2006

Hepatitis C virus (HCV) infection induces the α-chemokine interleukin-8 (CXCL-8), which is regulated at the levels of transcription and mRNA stability. In the current study, CXCL-8 regulation by double-stranded (ds)RNA pathways was analyzed in the context of HCV infection. A constitutively active mutant of the retinoic acid-inducible gene I (RIG-I), RIG-N, activated CXCL-8 transcription. Promoter mutagenesis experiments indicated that NF-κB and interferon (IFN)-stimulated response element (ISRE) binding sites were required for the RIG-N induction of CXCL-8 transcription. IFN-β promoter stimulator 1 (IPS-1) expression also activated CXCL-8 transcription, and mutations of the ISRE and NF-κB binding sites reduced and abrogated CXCL-8 transcription, respectively. In the presence of wild-type RIG-I, transfection of JFH-1 RNA or JFH-1 virus infection of Huh7.5.1 cells activated the CXCL-8 promoter. Expression of IFN regulatory factor 3 (IRF-3) stimulated transcription from both full-length and ISRE-driven CXCL-8 promoters. Chromatin immunoprecipitation assays demonstrated that IRF-3 and NF-κB bound directly to the CXCL-8 promoter in response to virus infection and dsRNA transfection. RIG-N stabilized CXCL-8 mRNA via the AU-rich element in the 3′ untranslated region of CXCL-8 mRNA, leading to an increase in its half-life following tumor necrosis factor alpha induction. The data indicate that HCV infection triggers dsRNA signaling pathways that induce CXCL-8 via transcriptional activation and mRNA stabilization and define a regulatory link between innate antiviral and inflammatory cellular responses to virus infection.
NKG2C
+
NK Cells Are Enriched in AIDS Patients with Advanced-Stage Kaposi's Sarcoma
Authors: Goodier Martin R. , Mela C. M. , Steel A. , Gazzard B. , Bower M. , Gotch F.
Published: December 2006

Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals with human immunodeficiency virus type 1 infection. We investigated the phenotype and function of the NKG2C
+
NK cell population in individuals with AIDS and Kaposi's sarcoma. The staging of AIDS KS patients according to the AIDS Clinical Trial Group criteria revealed that patients with the S1 disease stage have a significantly higher proportion of NKG2C
+
cells than those with the S0 disease stage. NKG2C
+
cells from S1-stage patients are highly enriched for the expression of KIR3DL1, are depleted of NKp46, and respond poorly to major histocompatibility complex class I-positive target cells. These data demonstrate a link between NK cell phenotype and function and disease prognosis in AIDS.
Adenovirus Type 5 Early Region 1B 156R Protein Promotes Cell Transformation Independently of Repression of p53-Stimulated Transcription
Authors: Sieber Timo , Dobner Thomas
Published: December 2006

Early region 1B (E1B) of adenovirus type 5 (Ad5) encodes at least five different polypeptides generated by alternative splicing of a common mRNA precursor. Two of these gene products, E1B-19K and E1B-55K, are individually capable of cooperating with the Ad5 E1A proteins to completely transform rodent cells in culture. Substantial evidence suggests that these two E1B proteins contribute to cell transformation by antagonizing growth arrest and apoptosis. Here, we performed genetic and biochemical analyses to assess the attributes of the remaining E1B proteins (E1B-156R, E1B-93R, and E1B-84R). Our results show that E1B-156R, which comprises the 79 amino-terminal and 77 carboxy-terminal amino acids of E1B-55K, also enhances focal transformation of primary rat cells in cooperation with E1A. Since E1B-156R seemed unable to relocalize p53 and inhibit its transactivating function, it must be assumed that it contributes to transformation independently of repression of p53-stimulated transcription. Furthermore, we discovered that E1B-156R contains a functional transcriptional repression domain and binds Ad5 E4orf6 and the cellular apoptosis regulator Daxx. While the ability to bind E4orf6 could indicate further biological functions of E1B-156R in viral infection, the interaction with Daxx might also be linked to its transforming potential. Taken together, these analyses introduce E1B-156R as a novel transformation-promoting E1B protein that acts without repressing p53 transactivation. Moreover, identification of the interaction partners E4orf6 and Daxx provides a first glance of E1B-156R's potential functions.
Glycoprotein L Disruption Reveals Two Functional Forms of the Murine Gammaherpesvirus 68 Glycoprotein H
Authors: Gillet Laurent , May Janet S. , Colaco Susanna , Stevenson Philip G.
Published: December 2006

The herpesvirus glycoprotein H (gH) and gL associate to form a heterodimer that plays a central role in virus-driven membrane fusion. When archetypal alpha- or betaherpesviruses lack gL, gH misfolds and progeny virions are noninfectious. In order to define the role that gL plays in gamma-2 herpesvirus infections, we disrupted its coding sequence in murine gammaherpesvirus-68 (MHV-68). MHV-68 lacking gL folded gH into a conformation antigenically distinct from the form that normally predominates on infected cells. gL-deficient virions bound less well than the wild type to epithelial cells and fibroblasts. However, they still incorporated gH and remained infectious. The cell-to-cell spread of gL-deficient viruses was remarkably normal, as was infection, dissemination, and latency establishment in vivo. Viral membrane fusion was therefore gL independent. The major function of gL appeared to be allowing gH to participate in cell binding prior to membrane fusion. This function was most important for the entry of MHV-68 virions into fibroblasts and epithelial cells.
M135R Is a Novel Cell Surface Virulence Factor of Myxoma Virus
Authors: Barrett John W. , Sypula Joanna , Wang Fuan , Alston Lindsay R. , Shao Zhuhong , Gao Xiujuan , Irvine Timothy S. , McFadden Grant
Published: December 2006

Myxoma virus (MV) encodes a cell surface protein (M135R) that is predicted to mimic the host alpha/beta interferon receptor (IFN-α/β-R) and thus prevent IFN-α/β from triggering a host antiviral response. This prediction is based on sequence similarity to B18R, the viral IFN-α/β-R from vaccinia virus (VV), which has been demonstrated to bind and inhibit type I interferons. However, M135R is only half the size of VV B18R. All other poxvirus-encoded IFN-α/β-R homologs align only to the amino-terminal half of M135R. Peptide antibodies raised against M135R were used for immunoblotting and immunofluorescence and indicate that M135R is expressed as an early gene and that the product is a cell surface N-linked glycoprotein that is not secreted. In contrast to the predicted properties of M135R as an inhibitor of type I interferon, all binding and inhibition assays designed to demonstrate whether M135R can interact with IFN-α/β have been negative. However, pathogenesis studies with a targeted M135-knockout MV construct (vMyx135KO) indicate that the deletion of M135R severely attenuates MV pathogenesis in the European rabbit. We propose that M135R is an important immunomodulatory virulence factor for myxomatosis but that the target immune ligand is not from the predicted type I interferon family and remains to be identified.
Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of
Mamu-B
*
17
-Containing Haplotypes
Authors: Wojcechowskyj Jason A. , Yant Levi J. , Wiseman Roger W. , O'Connor Shelby L. , O'Connor David H.
Published: December 2006

It is well established that host genetics, especially major histocompatibility complex (MHC) genes, are important determinants of human immunodeficiency virus disease progression. Studies with simian immunodeficiency virus (SIV)-infected Indian rhesus macaques have associated
Mamu-B
*
17
with control of virus replication. Using microsatellite haplotyping of the 5-Mb MHC region, we compared disease progression among SIVmac239-infected Indian rhesus macaques that possess
Mamu-B
*
17
-containing MHC haplotypes that are identical by descent. We discovered that SIV-infected animals possessing identical
Mamu-B
*
17
-containing haplotypes had widely divergent disease courses. Our results demonstrate that the inheritance of a particular
Mamu-B
*
17
-containing haplotype is not sufficient to predict SIV disease outcome.
Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius
Authors: Wiseman Roger W. , Wojcechowskyj Jason A. , Greene Justin M. , Blasky Alex J. , Gopon Tobias , Soma Taeko , Friedrich Thomas C. , O'Connor Shelby L. , O'Connor David H.
Published: December 2006

Nonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. Here we use microsatellite analysis to show that simian immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC genetics, with six common haplotypes accounting for two-thirds of the MHC haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques carry at least one complete copy of the most frequent MHC haplotype, and 8% of these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely conserved in unrelated Indian rhesus macaques. After intrarectal infection with highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus macaques mounted concordant cellular immune responses comparable to those previously reported for a pair of monozygotic twins infected with the same strain of human immunodeficiency virus. Our identification of relatively abundant SIV-susceptible, MHC-identical macaques will facilitate research into protective cellular immunity.
Role for Nonstructural Protein 1 of Severe Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation
Authors: Law Anna H. Y. , Lee Davy C. W. , Cheung Benny K. W. , Yim Howard C. H. , Lau Allan S. Y.
Published: December 2006

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. Since its associated morbidity and mortality have been postulated to be due to immune dysregulation, we investigated which of the viral proteins is responsible for chemokine overexpression. To delineate the viral and cellular factor interactions, the role of four SARS coronavirus proteins, including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were examined in terms of cytokine induction. Our results showed that the SARS coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in human lung epithelial cells via the activation of NF-κB.
Kinetic properties of chimeric class I aldehyde dehydrogenases for retinal isomers
Authors: Brodeur Hélène , Chagnon Samuel , Parisotto Maxime , Mader Sylvie , Bhat Pangala V.
Published: December 2006

Retinal dehydrogenase type 1 (RALDH1) catalyzes the oxidation of all-trans and 9-cis retinal to the respective retinoic acids (RAs), whereas another member of the aldehyde dehydrogenase (ALDH) family, the phenobarbital-induced aldehyde dehydrogenase (PB-ALDH), is very poorly active. We have previously generated chimeras between these 2 enzymes that displayed selectivity for retinal isomers in crude bacterial extracts. Here we have characterized the kinetic properties of the corresponding purified recombinant proteins. The all-trans selective chimera RALDH-131 converted all-trans retinal to all-trans RA with 2.9-fold lower efficiency than the wild-type RALDH1 and had only residual activity with 9-cis retinal. The converse chimera PB-131 was specific for 9-cis retinal, with no residual activity for all-trans retinal. MgCl2 inhibited the activities of RALDH1 and PB-131, but not of RALDH-131, suggesting that amino acids 132–510 in RALDH are necessary for inhibition by MgCl2. These data demonstrate that the chimeric enzymes act as retinal isomer-selective ALDHs, and suggest that these enzymes may be useful to study the roles of cis RA isomers in embryogenesis and differentiation in vivo.
Poly(ADP-ribosyl)ation regulates heat shock factor-1 activity and the heat shock response in murine fibroblasts
Authors: Fossati Silvia , Formentini Laura , Wang Zhao-Qi , Moroni Flavio , Chiarugi Alberto
Published: December 2006

Poly(ADP-ribose) polymerase-1 (PARP-1)-dependent poly(ADP-ribose) formation is emerging as a key regulator of transcriptional regulation, even though the targets and underlying molecular mechanisms have not yet been clearly identified. In this study, we gathered information on the role of PARP-1 activity in the heat shock response of mouse fibroblasts. We show that DNA binding of heat shock factor (HSF)-1 was impaired by PARP-1 activity in cellular extracts, and was higher in PARP-1−/−than in PARP-1+/+cells. No evidence for HSF-1 poly(ADP-ribosyl)ation or PARP-1 interaction was found, but a poly(ADP-ribose) binding motif was identified in the transcription factor amino acid sequence. Consistent with data on HSF-1, the expression of heat-shock protein (HSP)-70 and HSP–27 was facilitated in cells lacking PARP-1. Thermosensitivity, however, was higher in PARP-1−/−than in PARP-1+/+cells. Accordingly, we report that heat-shocked PARP-1 null fibroblasts showed an increased activation of proapoptotic JNK and decreased transcriptional efficiency of prosurvival NF-κB compared with wild-type counterparts. The data indicate that poly(ADP-ribosyl)ation finely regulates HSF-1 activity, and emphasize the complex role of PARP-1 in the heat-shock response of mammalian cells.
Downregulation of human endothelial nitric oxide synthase promoter activity by p38 mitogen-activated protein kinase activation
Authors: Xing Feiyue , Jiang Yong , Liu Jing , Zhao Kesen , Mo Yongyan , Liu Zhifeng , Zeng Yaoying
Published: December 2006

Human endothelial nitric oxide synthase (eNOS) plays a crucial role in maintaining blood pressure homeostasis and vascular integrity. eNOS gene expression may be upregulated by a signaling pathway, including PI-3Kγ → Jak2 → MEK1 → ERK1/2 → PP2A. It remains unclear whether other mitogen-activated protein kinase (MAPK) family members, such as JNK, p38 kinase, and ERK5/BMK1, also modulate eNOS gene expression. Our purpose, therefore, is to shed light on the effect of the p38 MAPK signaling pathway on the regulation of eNOS promoter activity. The results showed that a red fluorescent protein reporter gene vector containing the full length of the human eNOS promoter was first successfully constructed, expressing efficiently in ECV304 cells with the characteristics of real time observation. The wild-types of p38α, p38β, p38γ, and p38δ signal molecules all markedly downregulated promoter activity, which could be reversed by their negative mutants, including p38α (AF), p38β (AF), p38γ (AF), and p38δ (AF). Promoter activity was also significantly downregulated by MKK6b (E), an active mutant of an upstream kinase of p38 MAPK. The reduction in promoter activity by p38 MAPK could be blocked by treatment with a p38 MAPK specific inhibitor, SB203580. Moreover, the activation of endogenous p38 MAPK induced by lipopolysaccharide resulted in a prominent reduction in promoter activity. These findings strongly suggest that the activation of the p38 MAPK signaling pathway may be implicated in the downregulation of human eNOS promoter activity.
COMPRESSED PATTERN MATCHING IN JPEG IMAGES
Authors: KLEIN SHMUEL T. , SHAPIRA DANA
Published: December 2006

The possibility of applying compressed matching in JPEG encoded images is investigated and the problems raised by the scheme are discussed. A part of the problems can be solved by the use of some auxiliary data which yields various time/space trade-offs. Finally, approaches to deal with extensions such as allowing scaling or rotations are suggested.
FLEXIBLE MUSIC RETRIEVAL IN SUBLINEAR TIME
Authors: FREDRIKSSON KIMMO , MÄKINEN VELI , NAVARRO GONZALO
Published: December 2006

Music sequences can be treated as texts in order to perform music retrieval tasks on them. However, the text search problems that result from this modeling are unique to music retrieval. Up to date, several approaches derived from classical string matching have been proposed to cope with the new search problems, yet each problem had its own algorithms. In this paper we show that a technique recently developed for multipattern approximate string matching is flexible enough to be successfully extended to solve many different music retrieval problems, as well as combinations thereof not addressed before. We show that the resulting algorithms are average-optimal in many cases and close to average-optimal otherwise. Empirically, they are much better than existing approaches in many practical cases.