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1.
Ecol Appl ; 29(3): e01857, 2019 04.
Article in English | MEDLINE | ID: mdl-30680837

ABSTRACT

Worldwide, stocking of fish represents a valuable tool for conservation and maintenance of species exploited by recreational fishing. Releases of hatchery-reared fish are more and more recognized to have numerous demographic, ecological, and genetic impacts on wild populations. However, consequences on intraspecific trophic relationships have rarely been investigated. In this study, we assessed the impacts of supplementation stocking and resulting introgressive hybridization on the trophic niches occupied by stocked, local, and hybrid lake trout (Salvelinus namaycush) within populations of piscivorous and planktivorous ecotypes stocked from a wild piscivorous source population. We compared trophic niches using stable isotope analysis (δ13 C and δ15 N) and trophic position among the three genetic origins. Putative genetic effects were tested with phenotype-genotype association of "life history" ecological traits (body size, growth rate, condition index, and trophic niche) and genotypes (RADseq SNP markers) using redundant discriminant analysis (RDA). Results showed that sympatry resulting from the stocking of contrasting ecotypes is a risk factor for niche partitioning. Planktivorous populations are more susceptible to niche partitioning, by competitive exclusion of the local fish from a littoral niche to an alternative pelagic/profundal niche. Observed niche partitioning is probably a manifestation of competitive interactions between ecotypes. Our results emphasize that ecotypic variation should be considered for more efficient management and conservation practices and in order to mitigate negative impact of supplementation stocking.


Subject(s)
Ecotype , Gene-Environment Interaction , Animals , Ecology , Genotype , Trout
2.
J Fish Biol ; 88(5): 2088-94, 2016 May.
Article in English | MEDLINE | ID: mdl-27097972

ABSTRACT

The influences of additive, non-additive and maternal effects on early survival (uneyed embryo survival, eyed embryo survival, alevin survival and overall survival to first feeding) were quantified in lake trout Salvelinus namaycush using a 7 × 7 full-factorial breeding design. Maternal effects followed by non-additive genetic effects explained around one third of the phenotypic variance of the survival traits. Although the amount of additive genetic effects were low (<1%), suggesting a limited potential of the traits to respond to new selection pressures, how maternal and non-additive genetic effects may respond to selection under certain circumstances are discussed.


Subject(s)
Embryo, Nonmammalian , Mortality , Trout/genetics , Animals , Female , Lakes , Male , Maternal Inheritance , Phenotype , Survival Analysis
3.
Mucosal Immunol ; 9(1): 24-37, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25921339

ABSTRACT

HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c(+) and CD1c(neg)) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c(+) mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83(+)CD1c(+) mDCs negatively correlated with frequencies of interferon-γ-producing colon CD4(+) and CD8(+) T cells. CD40 expression on CD1c(+) mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c(+) mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Colon/immunology , Gastrointestinal Microbiome/immunology , HIV Infections/immunology , HIV-1/immunology , Mucous Membrane/immunology , Adult , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, CD1/genetics , Antigens, CD1/immunology , CD4-Positive T-Lymphocytes/microbiology , CD40 Antigens/genetics , CD40 Antigens/immunology , CD8-Positive T-Lymphocytes/microbiology , Case-Control Studies , Cell Lineage/immunology , Colon/microbiology , Dendritic Cells/immunology , Dendritic Cells/microbiology , Female , Gene Expression Regulation , Glycoproteins/genetics , Glycoproteins/immunology , HIV Infections/microbiology , HIV Infections/pathology , Humans , Immunoglobulins/genetics , Immunoglobulins/immunology , Interferon-gamma/genetics , Interferon-gamma/immunology , Lymphocyte Activation , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Middle Aged , Mucous Membrane/microbiology , Prevotella/growth & development , Prevotella/immunology , Ruminococcus/growth & development , Ruminococcus/immunology , Signal Transduction , Viral Load , CD83 Antigen
4.
J Fish Biol ; 86(4): 1438-43, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25753912

ABSTRACT

Juvenile Atlantic salmon Salmo salar from three allopatric populations (LaHave, Sebago and Saint-Jean) were placed into artificial streams with combinations of four non-native salmonids: brown trout Salmo trutta, rainbow trout Oncorhynchus mykiss, Chinook salmon Oncorhynchus tshawytscha and coho salmon Oncorhynchus kisutch. Non-additive effects, as evidenced by lower performance than predicted from weighted summed two-species competition trials, were detected for S. salar fork length (LF ) and mass, but not for survival, condition factor or riffle use. These data support emerging theory on niche overlap and species richness as factors that can lead to non-additive competition effects.


Subject(s)
Competitive Behavior , Salmo salar/physiology , Animals , Behavior, Animal , Body Size , Oncorhynchus kisutch/physiology , Oncorhynchus mykiss/physiology , Population Dynamics , Salmon/physiology
5.
Mucosal Immunol ; 7(4): 983-94, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24399150

ABSTRACT

Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.


Subject(s)
Endotoxemia/immunology , HIV Infections/immunology , HIV-1/immunology , Immunity , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Microbiota , Adult , Biodiversity , Biopsy , Body Mass Index , CD4 Lymphocyte Count , Colon/immunology , Colon/microbiology , Colon/pathology , Diet , Dysbiosis/immunology , Female , HIV Infections/virology , Humans , Intestinal Mucosa/pathology , Lymphocyte Activation/immunology , Male , Middle Aged , T-Lymphocyte Subsets/immunology , Viral Load , Young Adult
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 118: 828-34, 2014 Jan 24.
Article in English | MEDLINE | ID: mdl-24157334

ABSTRACT

On the way towards the development of a synthetic route aimed at obtaining new methylsilanediol derivatives with an aminocarbonyl group in ß to silicon (which may have a potential biological interest), we have synthesized, isolated and purified five diphenylic possible precursors, namely chloromethyl(methyl)diphenylsilane, 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione, N-[(methyl(diphenyl) silanyl)-methyl]-benzamide, N-[(methyl(diphenyl)silyl)-methyl]-acetamide and N-[(methyl(diphenyl)silyl)-methyl]-formamide. The conformational landscape of the five species in this study are explored by means of DFT calculations at the B3LYP/6-311++G(∗∗) level. The theoretical molecular structures predicted are confirmed by the reproduction of their respective IR and Raman spectral profiles, that are completely assigned. Some evidence in the vibrational spectra points to the occurrence of conformational mixtures in the samples. Further, single-crystal X-ray diffraction has allowed the elucidation of the crystalline structure of 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione.


Subject(s)
Silanes/chemistry , Crystallography, X-Ray , Methylation , Models, Molecular , Molecular Conformation , Quantum Theory , Silanes/chemical synthesis , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman
7.
Mucosal Immunol ; 7(3): 467-77, 2014 May.
Article in English | MEDLINE | ID: mdl-24045575

ABSTRACT

The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after 1 month of age, approaching adult densities later in infancy than both IgM and IgG. The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor a proliferation-inducing ligand (APRIL) and its receptors TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and B cell maturation antigen (BCMA) within isolated lymphoid follicles (ILFs). Moreover, both APRIL and BCMA expression strongly correlated with increasing IgA plasma cell densities over time. Conversely, TD mediators (CD40 ligand (CD40L) and CD40) were expressed within ILFs before 1 month and were not associated with IgA plasma cell generation. In addition, preterm infants had lower densities of IgA plasma cells and reduced APRIL expression compared with full-term infants. Thus, blunted TI responses may contribute to the delayed induction of intestinal IgA during early human infancy.


Subject(s)
Immunoglobulin A/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Plasma Cells/immunology , Plasma Cells/metabolism , Transmembrane Activator and CAML Interactor Protein/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism , B-Cell Maturation Antigen/genetics , B-Cell Maturation Antigen/immunology , B-Cell Maturation Antigen/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Cell Count , Child, Preschool , Cytidine Deaminase/genetics , Cytoplasm/metabolism , Female , Gene Expression , Humans , Immunoglobulin A/metabolism , Immunoglobulin Class Switching , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Immunoglobulin M/immunology , Immunoglobulin M/metabolism , Infant , Infant, Newborn , Infant, Premature , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Transmembrane Activator and CAML Interactor Protein/genetics , Tumor Necrosis Factor Ligand Superfamily Member 13/genetics
8.
Heredity (Edinb) ; 111(6): 513-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23942281

ABSTRACT

The additive genetic effects of traits can be used to predict evolutionary trajectories, such as responses to selection. Non-additive genetic and maternal environmental effects can also change evolutionary trajectories and influence phenotypes, but these effects have received less attention by researchers. We partitioned the phenotypic variance of survival and fitness-related traits into additive genetic, non-additive genetic and maternal environmental effects using a full-factorial breeding design within two allopatric populations of Atlantic salmon (Salmo salar). Maternal environmental effects were large at early life stages, but decreased during development, with non-additive genetic effects being most significant at later juvenile stages (alevin and fry). Non-additive genetic effects were also, on average, larger than additive genetic effects. The populations, generally, did not differ in the trait values or inferred genetic architecture of the traits. Any differences between the populations for trait values could be explained by maternal environmental effects. We discuss whether the similarities in architectures of these populations is the result of natural selection across a common juvenile environment.


Subject(s)
Quantitative Trait, Heritable , Salmo salar/genetics , Animals , Biological Evolution , Female , Male , Phenotype , Salmo salar/physiology , Selection, Genetic
9.
Gut ; 58(7): 964-73, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19193669

ABSTRACT

BACKGROUND: Dendritic cell (DC) defects may contribute to chronicity in hepatitis C virus (HCV) infection and determine response to PEG-interferon and ribavirin therapy via poor T cell stimulation. Studies to date have produced inconsistent results regarding DC maturation and function: no large study has examined DCs before and after therapy. AIMS: We examined if DC defects in maturation and chemotaxis are present by comparing therapeutic responders to non-responders. METHODS: We analysed peripheral DCs of 64 HCV genotype 1-infected patients from the Virahep-C study 2 weeks before and 24 weeks after therapy. We used flow cytometry to enumerate plasmacytoid DC (pDC) and myeloid DCs (mDC) and quantify expression of chemokine receptors and maturation markers. Chemotaxis was measured with an in vitro assay. RESULTS: Pre-treatment frequencies of pDCs and mDCs were significantly lower in HCV patients than controls and successful therapy normalised pDCs. Levels of CXCR3 and CXCR4 on pDCs were higher at baseline compared to normal controls and decreased with therapy. Pre-therapy levels of co-stimulatory marker CD40 and the maturation marker CD83 were higher in pDCs of patients chronically infected with HCV compared to normal patients, and levels of both markers dropped significantly with therapy in the SVR+ group only. Other maturation markers (CD86 and CCR7) were not elevated suggesting a partially activated phenotype. Baseline chemotaxis of pDCs to CXCL12 and CXCL10 predicted failure of antiviral response and correlated with the histological activity index inflammation score. CONCLUSIONS: Plasmacytoid DC defects exist in chronic HCV and successful antiviral therapy normalises many phenotypic and functional abnormalities.


Subject(s)
Antiviral Agents/therapeutic use , Chemotaxis/immunology , Dendritic Cells/immunology , Hepatitis C, Chronic/immunology , Receptors, Chemokine/immunology , T-Lymphocytes/immunology , Adult , Chemotaxis/drug effects , Dendritic Cells/drug effects , Dendritic Cells/virology , Female , Flow Cytometry , Genotype , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Receptors, Chemokine/drug effects , T-Lymphocytes/drug effects , Treatment Outcome
10.
Acta Crystallogr B ; 64(Pt 1): 57-65, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18204212

ABSTRACT

Automated cluster analysis is used to examine the conformation and configuration of pyranose sugars. Previous findings on this issue are confirmed, importantly from an analysis that requires no prior knowledge of the significant factors determining the conformational classification. The findings on the conformations adopted in the crystalline solid state are found to be different to existing quantum chemical calculations performed for D-glucose in the gas phase, but consistent with empirically determined conformations in the solution state. The use of this clustering analysis in studying chirality in the determined structures is discussed, as is the ability of this type of method to examine higher dimensions within the metric multi-dimensional scaling formalism.

11.
Forensic Sci Int ; 166(1): 68-76, 2007 Feb 14.
Article in English | MEDLINE | ID: mdl-16690237

ABSTRACT

The use of DNA in forensics has grown rapidly for human applications along with the concomitant development of bioinformatics and demographic databases to help fully realize the potential of this molecular information. Similar techniques are also used routinely in many wildlife cases, such as species identification in food products, poaching and the illegal trade of endangered species. The use of molecular techniques in forensic cases related to wildlife and the development of associated databases has, however, mainly focused on large mammals with the exception of a few high-profile species. There is a need to develop similar databases for aquatic species for fisheries enforcement, given the large number of exploited and endangered fish species, the intensity of exploitation, and challenges in identifying species and their derived products. We sequenced a 500bp fragment of the mitochondrial cytochrome b gene from representative individuals from 26 harvested fish taxa from Ontario, Canada, focusing on species that support major commercial and recreational fisheries. Ontario provides a unique model system for the development of a fish species database, as the province contains an evolutionarily diverse array of freshwater fish families representing more than one third of all freshwater fish in Canada. Inter- and intraspecific sequence comparisons using phylogenetic analysis and a BLAST search algorithm provided rigorous statistical metrics for species identification. This methodology and these data will aid in fisheries enforcement, providing a tool to easily and accurately identify fish species in enforcement investigations that would have otherwise been difficult or impossible to pursue.


Subject(s)
DNA, Mitochondrial/analysis , Fishes/genetics , Animals , Extinction, Biological , Fishes/classification , Forensic Pathology , Fresh Water , Ontario
13.
J Virol ; 76(12): 5925-36, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12021325

ABSTRACT

One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4(+) T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4(+) Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infected subjects with active in vivo viral replication versus those on suppressed highly active antiretroviral therapy (HAART). No statistically significant differences in the frequencies of cytokine-secreting, HIV-1-specific CD4(+) T cells between the donor groups were found, despite differences in viral load and treatment status. However, HIV-1-specific lymphoproliferative responses were significantly greater in the subjects with HAART suppression than in subjects with active viral replication. Similar levels of HIV-1 RNA were measured in T-cell cultures stimulated with HIV-1 antigens regardless of donor in vivo viral loads, but only HIV-1-specific CD4(+) T cells from subjects with HAART suppression proliferated in vitro, suggesting that HIV-1 replication in vitro does not preclude HIV-1-specific lymphoproliferation. This study demonstrates a discordance between the frequency and proliferative capacity of HIV-1-specific CD4(+) T cells in subjects with ongoing in vivo viral replication and suggests that in vivo HIV-1 replication contributes to the observed defect in HIV-1-specific CD4(+) T-cell proliferation.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/virology , HIV-1/immunology , Interferon-gamma/biosynthesis , Lymphocyte Activation/immunology , Virus Replication , Adult , Antigens, CD/immunology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/immunology , Antigens, Differentiation, T-Lymphocyte/metabolism , Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/metabolism , HIV Core Protein p24/immunology , HIV Core Protein p24/metabolism , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/drug effects , HIV-1/physiology , Humans , Lectins, C-Type , RNA, Viral/blood , Viral Load
14.
Acta Crystallogr B ; 57(Pt 4): 560-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11468383

ABSTRACT

The structure of the title compound has been determined using low-temperature (150 K) single-crystal X-ray and neutron diffraction data. Crystals adopt the uncommon space group P4(2)/ncm and display a complex set of intermolecular interactions in which the water molecules play the crucial role: the water O-atom [O2(w)] accepts two hydrogen bonds and both water H atoms act as bifurcated donors. A set of O--H...O hydrogen bonds is formed around the 4(2) axis comprising (a) a cyclic tetrameric synthon involving four donor-H from two water molecules and two O(hydroxy) acceptors from two parent molecules, and (b) short discrete O(hydroxy)--H...O2(w) hydrogen bonds which link these tetramers along the c axis. Four Br...Br interactions [3.708 (1) A] form cyclic Br(4) tetramers around the 4 axis and are linked to the O--H...O system via O2(w)--H...Br bonds with H...Br = 2.995 (2) A. Finally, the O--H...O system is further linked to the parent molecules via C identical with C...H...O2(w) bonds of 2.354 (3) A. The supramolecular structure of the title hydrate is compared with that of the non-hydrated parent molecule, which also forms cyclic O--H...O bonded tetrameric synthons, and with its (non-hydrated) tetrachloro analogue, which forms cyclic tetrameric Cl(4) synthons [Madhavi, Desiraju et al. (2000b). Acta Cryst. B56, 1063--1070].

15.
Evolution ; 55(3): 573-86, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11327164

ABSTRACT

This study evaluated mitochondrial DNA (mtDNA) sequence variation in a 552-bp fragment of the control region of Arctic charr (Salvelinus alpinus) by analyzing 159 individuals from 83 populations throughout the entire range of the complex. A total of 89 (16.1%) nucleotide positions were polymorphic, and these defined 63 haplotypes. Phylogenetic analyses supported the monophyly of the complex and assigned the observed haplotypes to five geographic regions that may be associated with different glacial refugia. Most notably, a formerly defined major evolutionary lineage (S. a. erythrinus) ranging from North America across the Arctic archipelago to the Eurasian continent has now been partitioned into the Arctic group and the newly identified Siberian group. The Beringian group, formed entirely by specimens assigned to S. malma (Dolly Varden), encompassed the area formerly assigned to S. a. taranetzi. The latter, due to a unique haplotype, became the basal member of the Arctic group. Overall, the S. alpinus complex reflects divergent evolutionary groups coupled with shallow intergroup differentiation, also indicated by an analysis of molecular variance that attributed 73.7% (P < 0.001) of the total genetic variance among groups. Time estimates, based on sequence divergence, suggest a separation of the major phylogeographic groups during early to mid-Pleistocene. In contrast, colonization of most of today's range started relatively recently, most likely late Pleistocene during the last retreat of ice sheets some 10,000-20,000 years ago. This time scale obviously is too shallow for detecting significant variation on a smaller scale using mtDNA markers. However, other studies using nuclear microsatellite DNA variation strongly suggested ongoing evolution within groups by revealing strong population-genetic substructuring and restricted gene flow among populations. Thus, Arctic charr could serve as a model organism to investigate the linkage between historical and contemporary components of phylogeographic structuring in fish, and, with a global perspective of the distribution of genetic variation as a framework, meaningful comparisons of charr studies at a smaller geographic scale will now be possible.


Subject(s)
DNA, Mitochondrial/genetics , Evolution, Molecular , Genetic Variation , Phylogeny , Trout/genetics , Animals , Arctic Regions , Base Sequence , Locus Control Region/genetics , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Trout/classification
16.
Nat Med ; 7(5): 625-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11329066

ABSTRACT

There is currently a need for vaccines that stimulate cell-mediated immunity-particularly that mediated by CD8+ cytotoxic T lymphocytes (CTLs)-against viral and tumor antigens. The optimal induction of cell-mediated immunity requires the presentation of antigens by specialized cells of the immune system called dendritic cells (DCs). DCs are unique in their ability to process exogenous antigens via the major histocompatibility complex (MHC) class I pathway as well as in their ability to activate naive, antigen-specific CD8+ and CD4+ T cells. Vaccine strategies that target or activate DCs in order to elicit potent CTL-mediated immunity are the subject of intense research. We report here that whole recombinant Saccharomyces cerevisiae yeast expressing tumor or HIV-1 antigens potently induced antigen-specific, CTL responses, including those mediating tumor protection, in vaccinated animals. Interactions between yeast and DCs led to DC maturation, IL-12 production and the efficient priming of MHC class I- and class II-restricted, antigen-specific T-cell responses. Yeast exerted a strong adjuvant effect, augmenting DC presentation of exogenous whole-protein antigen to MHC class I- and class II-restricted T cells. Recombinant yeast represent a novel vaccine strategy for the induction of broad-based cellular immune responses.


Subject(s)
AIDS Vaccines/immunology , Dendritic Cells/immunology , Immunity, Cellular , Saccharomyces cerevisiae/genetics , Vaccines, Synthetic/immunology , Animals , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Mice , Mice, Transgenic
17.
Acta Crystallogr B ; 57(Pt 3): 435-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11373405

ABSTRACT

The structure of urea-phosphoric acid is reported at a large number of temperatures in the range 150-335 K from neutron diffraction data collected using a novel multiple single-crystal data collection method. The work focuses on the behaviour of the H atom involved in the short strong O-H.O hydrogen bond in this material. The position of this atom is shown to vary significantly, by around 0.035 A, as a function of temperature, becoming effectively centred at the highest temperatures studied. This result, only accessible due to the accurate determination of H-atom parameters by neutron diffraction, has implications for the potential governing the hydrogen bond.

18.
J Virol ; 75(9): 4195-207, 2001 May.
Article in English | MEDLINE | ID: mdl-11287569

ABSTRACT

Human immunodeficiency virus (HIV)-specific helper T lymphocytes (HTL) play a key role in the immune control of HIV type 1 (HIV-1) infection, and as such are an important target of potential HIV-1 vaccines. In order to identify HTL epitopes in HIV-1 that might serve as vaccine targets, conserved HIV-1-derived peptides bearing an HLA-DR binding supermotif were tested for binding to a panel of the most representative HLA-DR molecules. Eleven highly cross-reactive binding peptides were identified: three in Gag and eight in Pol. Lymphoproliferative responses to this panel of peptides, as well as to the HIV-1 p24 and p66 proteins, were evaluated with a cohort of 31 HIV-1-infected patients. All 11 peptides were recognized by peripheral blood mononuclear cells from multiple HIV-infected donors. Many of the responsive HIV-infected subjects showed recognition of multiple peptides, indicating that HIV-1-specific T-helper responses may be broadly directed in certain individuals. A strong association existed between recognition of the parental recombinant HIV-1 protein and the corresponding HTL peptides, suggesting that these peptides represent epitopes that are processed and presented during the course of HIV-1 infection. Lastly, responses to the supermotif peptides were mediated by CD4(+) T cells and were restricted by major histocompatibility complex class II molecules. The epitopes described herein are potentially important components of HIV-1 therapeutic and prophylactic vaccines.


Subject(s)
Epitopes, T-Lymphocyte/immunology , HIV Antigens/immunology , HIV-1/immunology , HLA-DR Antigens/immunology , T-Lymphocytes, Helper-Inducer/immunology , Amino Acid Sequence , Antigen Presentation/immunology , CD4-Positive T-Lymphocytes/immunology , Cell Division , Cross Reactions , Epitope Mapping , HIV Infections/immunology , Humans , Molecular Sequence Data , Peptides/immunology
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