bluuebunny/crossref_metadata_2025 huggingface dataset:
Similar abnormalities of idiotype and immunoglobulin light chain expression and of cell‐mediated cytotoxicity in HIV‐infected humans and simian immunodeficiency virus (SIV)‐infected rhesus macaques
Authors: GRANT MD , WHALEY MD , MAYNE A , HOFFMANN GW , ANSARI AA
Published: June 2007

The pathogenesis of AIDS in simian immunodeficiency virus (SIV)‐infected rhesus macaques models the pathogenesis of human AIDS. We investigated whether certain immunological abnormalities associated with HIV infection and implicated in disease progression also occur in SIV infection. We observed striking parallels between the rhesus macaque humoral immune response to SIV and unusual features of the human humoral immune response to HIV infection. Anti‐SIV envelope antibodies from SIV‐infected macaques exhibited skewed K/λ L chain usage relative to the ratio of K/λ L chain usage detected on total plasma Ig. In addition, the same idiotope conserved on human anti‐HIV gag, pol and env antibodies was detected with a similar distribution pattern on macaque anti‐SIV env, gag and pol antibodies. Skewed Ig L chain representation and selection of a highly conserved possible dominant regulatory idiotope on antibodies against key neutralizing antigens raise the possibility that the progressive failure of the humoral immune response to SIV and HIV involves skewed oligoclonal humoral immunity. We also found that SIV‐infected macaques, like HIV‐infected humans, have elevated levels of CD8+ lymphocyte‐mediated cytotoxicity. Cytotoxicity against human B cells was higher in CD8+ effector lymphocytes from SIV‐infected macaques than in those from uninfected macaques (P <0.05). Cell‐mediated cytotoxicity against human NK cell targets was not elevated in effector lymphocytes from the SIV‐infected macaques, suggesting that CTL activity was selectively elevated. Two out of seven SIV‐infected macaques tested had CD8+ cytotoxic lymphocytes that selectively killed activated uninfected CD4+ macaque lymphocytes. Oligoclonal B cell responses and persistently elevated CD+ lymphocyte‐mediated cytotoxicity are consistent features of primate retroviral infections leading to AIDS. Understanding immune predispositions to these features triggered by HIV and SIV may advance new prophylactic and therapeutic strategies.
How adaptive antibodies facilitate the evolution of natural antibodies
Authors: ANDERSON RUSSELL WAYNE
Published: June 2007

It is shown how Ig specificities, randomly generated in conventional B cells, come to be expressed in the genetically‐determinate B1 population. Thus the adaptive antibody population facilitates the evolution of the natural antibody repertoire, in accordance with the Baldwin effect in the evolution of instinct. The evolution of these two populations is discussed under both the‘proximal usage’and‘preferential expression’hypotheses of biased Ig gene segment usage. This process is independent of theories of B1 function.
Expression of the T cell receptor δ‐chain repertoire in mouse lymph node
Authors: OLIVE COLLEEN
Published: June 2007

Despite the potential for extensive diversity of γδ TCR, especially for δ‐chains, expression of the γδ TCR repertoire in various mouse epithelial tissues is highly restricted. This implies that the recognition of antigen by γδ T cells may also be limited. To date, however, few studies have examined γδ TCR diversity in peripheral lymphoid tissue. This report presents the Vδ usage and junctional region sequences of TCR δ‐chain transcripts derived from the lymph nodes of normal (PL/J × SJ/L) Fl mice. Rearranged TCR Vδ‐Cδ transcripts were amplified by PCR from TCR δ‐chain cDNA using oligonucieotide primers specific for the murine Vδl to Vγδ7 genes and the Cδ region. Following cloning of the polymerase chain reaction‐amplified TCR δ cDNA, the extent of junctional diversity was assessed by nucleotide sequencing of the V‐D‐J junctions of individual TCR cDNA clones. With the exception of Vδ3, all Vδ genes were expressed in mouse lymph node. Furthermore, predominant usage of Jδ1 was found in cDNA clones expressing Vδ2. Vδ4, Vδ5. Vδ6 and Vδ7 gene segments but despite this there was extensive junctional diversity of δ‐chains primarily due to the usage of multiple Dδ segments and N‐nucleotide sequence addition. In contrast, the Vδl cDNA clones had limited heterogeneity consisting mostly of Vδ1 directly spliced to γδ gene rearrangements. These results show that the expressed murine peripheral TCR δ‐chain repertoire is extremely diverse indicating that γδ T cells may potentially recognize a large number of antigens, and play an important role in contributing to host immune responses.
The PCR typing of MHC‐DRB genes in the sheep using primers for an intronic microsatellite: Application to nematode parasite resistance
Authors: OUTTERIDGE PM , ANDERSSON L , DOUCH PGC , GREEN RS , GWAKISA PS , HOHENHAUS MA , MIKKO S
Published: June 2007

The strong association between polymorphisms in an intronic microsatellite and the coding sequences for (BoLA)‐DRB3 genes, previously described for demonstrating alleles of class II major histocompatibility complex (MHC) in the cow, was examined in sheep to see if similar polymorphisms could be demonstrated in the DRB region of the MHC. The bovine primers LA53 and LA54, previously used to amplify the bovine DRB3 microsatellites, were used with DNA from Australian sheep, eight DRB alleles were identified by length polymorphisms of polymerase chain reaction (PCR) products amplified from the DRB microsatellite region. Incomplete amplification of both alleles was sometimes found for sheep DNA samples using bovine primers, so a modified primer (LA53b) was used, and found to amplify the microsatellite next to intron 2 of the MHC more reliably than the LA53 primer. Two additional primers (LA31 and LA32), used in amplification of the exon 2 region of bovine DRB3, were used in the sheep, and the PCR products were analysed by single‐stranded conformation polymorphism (SSCP). These primers successfully amplified the variable region of the ovine DRB region coded by exon 2, and the SSCP technique demonstrated polymorphisms with sheep DNA. Family studies demonstrated the segregation of alleles, by amplification both of intronic microsatellites and of the exon 2 variable region. Close correspondence was found between the two regions for several alleles, suggesting that the intronic microsatellites were closely linked to DRB‐variable region alleles. Three families of Merino sheep with different antibody responses to intestinal nematode parasites were examined. The sire group with the highest antibody levels possessed two microsatellite alleles of closely similar length (alleles 3 and 4) inherited from the sire and present in high frequency in the lambs. In contrast, the other two sires did not possess these two alleles and the alleles were in low frequency in their progeny. Further studies are required in unrelated sheep to confirm whether these two alleles are associated with resistance to nematode parasites.
Bacterial metabolism, cytokine mRNA transcription and viability of bovine alveolar macrophages infected with Mycobacterium bovis BCG or virulent M bovis
Authors: ALDWELL FE , WEDLOCK DN , BUDDLE BM
Published: June 2007

Mycobacterium bovis causes tuberculosis in cattle and many other animals including humans while BCG, an attenuated form of M. bovis, has been used widely as a safe vaccine. Both strains infect host macrophages and their fate is determined by their ability to survive within these phagocytic cells. We compared interactions of these two strains with bovine alveolar macrophages in order to gain an understanding of virulence mechanisms involved in the early pathogenesis of M. bovis infection. Macrophages were infected with bacilli at varying multiplicities of infection and cultured for 1‐4 days. Bacterial metabolism within macrophages was assessed by [3H]‐uracil uptake and bacterial growth was assessed by culture and acid‐fast staining. Induction of TNF‐α, IL‐1β and IL‐6 cytokine mRNA transcription in macrophages was determined by reverse transcriptase‐polymerase chain reaction. Infection of macrophages by virulent M. bovis resulted in enhanced bacterial metabolism, enhanced induction of macrophage cytokines and reduced viability of macrophages when compared to M. bovis BCG‐infected macrophages. These differences may reflect virulence mechanisms contributing to the early pathogenesis of bovine tuberculosis.
IgE, allergies and helminth parasites: A new perspective on an old conundrum
Authors: BELL RG
Published: June 2007

This paper analyses the association between infection with helminth parasites, the elevated production of IgE and the expression of allergies. Interpretations of this interaction have taken place in a scientific environment whose most secure element is the immunochemistry of allergic reactions resulting in a substantial body of literature that has sought a biological role for allergic reactivity in protective immunity directed against helminth parasites. While the association between helminth infections and elevated levels of IgE, mast cells and eosinophils is well established, a functional role for allergic reactions in protection against helminths has eluded experimental proof. Instead of this hypothesis, it is proposed that allergic reactivity is rarely present in helminth‐infected individuals because allergic reactions do not function to regulate helminth infections. Data from many sources are used to establish that the ‘normal’ state of all mammals is to be infected with helminth parasites from shortly after birth until well into adulthood. Only in the last 100 years or so have people living in areas of high development with sophisticated water and sewage systems been able to escape helminth infection. Allergies are as conspicuously present in these human populations as they are absent in populations that are still regularly exposed to helminths. Furthermore, in populations with endemic helminthoses there is little overt expression of allergic pathology that could be connected to the acquisition or elimination of helminth parasites. Based on these observations, it is suggested that endemic helminthoses activate the Th2 system, particularly at mucosal surfaces, to provide a different level of immunological homeostasis than currently occurs in developed societies. Under these conditions, mast cells, eosinophils and IgE rarely participate in reactions that we would recognize as ‘allergic’, although their participation in the control of helminth infections is still envisaged. Allergic reactions are considered to be a purely pathologic consequence of the disruption of this homeostatic mechanism and are not protective at all for the individual expressing them. This interpretation is derived from the immunobiology of the host‐parasite interaction rather than the biology of allergies and should lead to new concepts regarding both allergic disease and the role of helminth infections in human and animal populations.
The effect of BCG, zymosan and Coxiella burnetti extract on Eimeria infections
Authors: SMITH NC , OVINGTON KS
Published: June 2007

Infection of animals with species of Eimeria induces a hyper‐reactivity to endotoxin as manifest by a greatly increased capacity of infected animals to produce TNF in response to LPS in vivo compared with uninfected animals. This finding indicates priming for hyperactivation of macrophages by Eimeria infection and raises the possibility that non‐specific triggering of macrophages by agents such as Bacille Calmette‐Guerin (BCG), zymosan or Coxiella burnetti extract may be a simple means of control for coccidiosis. However, all of these agents enhanced oocyst excretion in mice, rats or chickens infected with Eimeria vermiformis. Eimeria nieschulzi or Eimeria tenella, respectively, without affecting the patent period.
Evolution of MHC class I genes in higher primates
Authors: LIENERT KRISTIN , PARHAM PETER
Published: June 2007

The classical major histocompatibility complex (MHC) class I genes are conserved in higher primates. Motifs common to human, chimpanzee and gorilla alleles indicate that class I alleles diverged from ancestral sequences that existed before separation of these species. Analysis of native human populations such as Australian Aborigines and Amerindians shows that HLA‐B is characterized by rapid generation of new alleles. HLA‐A and ‐C appear to be evolving more slowly. Comparison of alleles for orthologous class I genes in humans and other primates confirms that similar mechanisms contribute to the generation of new alleles in these species.
Heavy‐chain variable regions in carcharhine sharks: Development of a comprehensive model for the evolution of VH domains among the gnathanstomes
Authors: SHEN SHAN XIANG , BERNSTEIN RALPH M , SCHLUTER SAMUEL F , MARCHALONIS JOHN J
Published: June 2007

We determined the sequence of 18 DNA clones encoding VH regions of sandbar shark and bull shark. All of these sequences exhibit key structural coding features characteristic of known VH genes of higher vertebrates. These VH sequences disclosed considerable diversity, and can be divided into six families according to the criterion of 80% DNA sequence identity. The overlapping of some VH gene clones to two or more families is a particular feature found in carcharhine sharks, which suggests that VH diversification is a continuing process. The basic sequence patterns of heavy‐chain V regions found in all representative gnathanstomes and in VH of the shark heavy immunoglobulin igW provides evidence for selection of canonical residues in all VH structures, Elasmobranch VH sequences can be divided into two classes or clans, one comprising the ‘classical’ VH set and the other comprising VHs related to those of IgW (Vω). Phylogenetic analyses place the VH cluster as the root of all the classic VHs and indicates that the Vω set is most probably that of the primordial heavy chain.
NK‐like activity against allogeneic tumour cells demonstrated in the spleen of control and thymectomized Xenopus
Authors: HORTON TRUDY L , RITCHIE PAMELA , WATSON MARTIN D , HORTON JOHN D
Published: June 2007

This paper addresses the issue of natural killer (NK) cell evolution by searching for NK‐like activity in an amphibian representative, the immunologically well‐characterized clawed frog. Xenopus laevis. Using in vitro6 h 51 chromium release assays, we have shown that splenocyte effectors from early thymectomized (Tx) year‐old frogs, but not from control siblings, are able to spontaneously lyse allogeneic thymus tumour cell lines that lack MHC antigen expression. Such lytic capacity can be readily induced in control Xenopus and elevated in Tx frogs by a single injection of tumour cells, with maximal splenocyte cytotoxicity occurring 3 days postinjection, the amount of 51 Cr‐release correlating directly with effector: target ratios. Splenocytes, even those from tumour‐injected frogs, are unable to lyse allogeneic splenic lymphoblasts or erythrocyte targets, even when the latter are coated with IgY (the Xenopus IgG equivalent); moreover, we were unable to demonstrate any splenocyte‐induced lysis of the human NK cell target K562. Lymphokine‐activated killing (LAK) in Xenopus is suggested, since Tx splenocytes cultured in cytokine‐rich medium (from concanavalin A‐stimulated control splenocytes) display significantly elevated killing of allogeneic tumour targets. Flow cytometric analysis highlights the loss of T cell markers from the spleen of Tx frogs and reveals a variable staining pattern of both control and Tx splenocytes when treated with a mAb that binds to both fish non‐specific cytotoxic cells and human NK cells. Prospects for identifying the cellular basis of NK‐like activity in Xenopus are discussed in the light of these experiments.
A partial sequence for nitric oxide synthase from a goldfish (Carassius auratus) macrophage cell line
Authors: LAING KJ , GRABOWSKI PS , BELOSEVIC M , SECOMBES CJ
Published: June 2007

Expression of inducible nitric oxide synthase (iNOS) mRNA was detected in a recently developed goldfish macrophage cell line by RT‐PCR. using degenerate primers designed against conserved nucleotide motifs within the different mammalian isoforms of NOS. Increased expression of iNOS poststimulation with LPS was found, and suggests that it is a functional enzyme in goldfish macrophages. supporting the view that iNOS regulation is pretranslational. The nucleotide sequence translated in one reading frame with no stop codons to produce a partial peptide containing 164 amino acids, with highest homology (85%) to a recently identified rainbow trout iNOS sequence. The peptide translation also gave an insight into the conservation of binding motifs, since two cofactor binding sites were present in the amplified PCR product (FMN and calmodulin). In addition, a 42 aa motif present in the region just upstream of the FMN binding motif of mammalian endothelial and neuronal NOS isoforms was absent in the translation, in agreement with every published sequence for iNOS. Finally, the translation was used to construct an unrooted phylogenetic tree.
Interaction of monocytoid cells with the mucosal addressin MAdCAM‐1 via the integrins VLA‐4 and LPAM‐1
Authors: YANG YI , HARRISON JANE EB , PRINT CRISTIN G , LEHNERT KLAUS , SAMMAR MAREI , LAZAROVITS ANDREW , KRISSANSEN GEOFFREY W
Published: June 2007

The differentiation of myeloid cells into macrophages and granulocytes is accompanied by marked changes in adhesive phenotype. Here we seek to understand the regulation of expression and functionality of the VLA‐4 (α4βl). LPAM‐I (α4β7) and HML‐I (αEβ7) integrins on monocytes/macrophages and granulocytes, given that these integrins including LFA‐I (αLβ2) mediate the entry, retention and signalling events of pathogenic leucocytes within chronically inflamed tissues. Phorbol ester‐induced monocytic differentiation of the promyelocyte cell line HL60 led to increases in the steady‐state levels of β2 and β7 mRNA transcripts, requiring a period of 10 and 24 h. respectively, of de novo protein synthesis. There was a parallel de now expression of LPAM‐1 on the cell surface, despite the fact that a4 mRNA transcripts were rapidly down regulated. At 72 h. HML‐1 was not coexpressed with LPAM‐1 on HL60 cells, although it was weakly expressed on peripheral blood monocytes/macrophages after a prolonged period of in vitro culture. Retinoic acidinduced granulocytic differentiation of HL60 cells led to the appearance of low levels of LPAM‐1 at the cell surface. LPAM‐1 was not found expressed on peripheral blood neutrophils, raising the possibility that it is transiently expressed during granulocyte differentiation. In accord with the above findings, differentiated monocytes and HL60 cells bound to recombinant MAdCAM‐1 in an α4‐ and β7‐integrin‐dependent fashion, whereas a population of undifferentiated HL60 cells and Mn ++‐activated monocytes bound in an α4‐integrindependent β7‐integrin‐independent manner via VLA‐4 expressed abundantly at all stages of differentiation. Four h after attachment, some of these VLA‐4+ LPAM‐1‐ HL60 cells could be seen to start spreading. These findings suggest that MAdCAM‐l can bind to VLA‐4 when LPAM‐1 is absent, and thus has the potential to recruit both VLA‐4‐bearing monocytes and VLA‐4+ LPAM‐1+ macrophages into chronically inflamed tissues.
Memory alloreactive cytotoxic T cells do not require costimulation for activation in vitro
Authors: FLYNN KIRSTEN , MÜLLBACHER ARNO
Published: June 2007

We have studied the costimulation requirements for the generation of cytotoxic T (Tc) cells in an in vitro recall response to alloantigens. Firstly, we demonstrate that recombinant vaccinia viruses encoding class I MHC can stimulate primary in vivo responses and prime for secondary in vitro responses specific for the immunizing alloantigen. The secondary in vitro response comprises both naive and memory components that are distinguishable kinetically. Naive alloreactive Tc cell precursors are dependent upon the presence of CD80 on the in vitro stimulating population for activation and generation of effector function, as described previously.1 However, Tc cells from animals primed in vivo with vaccinia virus (VV) encoding allo‐MHC do not require CD28‐CD80 interactions to respond to the alloantigen presented in vitro. This finding provides further evidence that memory Tc cells have less stringent activation requirements in vitro than naive cells. From limiting dilution analysis of the relative contribution of naive and memory Tc cell precursors in ‘primary’ responses, to MHC class I alloantigen, memory alloreactive Tc cell1 precursors, possibly primed by cross‐reactive environmental antigens, contribute approximately one‐fifth of the precursors. Memory responses exhibit similar precursor frequencies as primary responses. Thus, we conclude that memory is largely a result of qualitative rather than quantitative changes in Te cell precursors.
Tumour necrosis factor‐alpha (TNF‐α): The good, the bad and potentially very effective
Authors: BARBARA JEFFREY AJ , VAN OSTADE XAVEER , LOPEZ ANGEL F
Published: June 2007

When the tumour necrosis factor‐alpha (TNF‐α) gene was cloned the protein became available for use in clinical trials as an antineoplastic agent. However, side effects have severely limited its application in cancer treatment. Studies on the species specificity of TNF have indicated that the p75 TNF receptor (TNFR75) may play an important role in the generation of these side effects in humans. Using human TNF mutants with selective receptor‐binding properties it has been demonstrated in neutrophils and endothelium that TNFR75 is involved in the mediation of the proinflammatory activity of TNF by facilitating the p55 TNF receptor (TNFR55). However, only TNFR55 appears to be involved in mediating TNF cytotoxicity. Therefore the potential exists for the successful reintroduction of TNF‐α, in the form of TNFR55‐selective mutants, into the clinical arena with the promise of reduced side effects.
Peptide binding function and the paradox of HLA disease associations
Authors: HUGHES AUSTIN L , YEAGER MEREDITH , CARRINGTON MARY
Published: June 2007

Many studies have found associations between HLA loci and susceptibility or resistance to both infectious and autoimmune diseases, but often subsequent studies fail to find the same association. Such inconsistencies are not surprising if we consider what is known of the population biology and evolution of HLA genes, especially the consequences of natural selection favouring heterozygosity in the peptide binding regions (PBR) of HLA molecules. Because of past recombination events and/or convergent evolution, alleles that are not closely related in overall sequence may come to resemble each other in the PBR. Because peptide binding is likely to be important for the role of HLA molecules in both infectious and autoimmune disease, a strategy of searching for HLA disease associations that groups alleles in functional categories based on PBR motifs may prove more successful than conventional strategies. Likewise, in developing approaches for molecular typing, it may be advisable to develop methods that group alleles on the basis of shared PBR motifs rather than simply on the basis of shared primer sites in less functionally important regions.
Immune deviation: A historical perspective*
Authors: PARISH CHRISTOPHER R
Published: June 2007

In this paper I have reviewed my early studies, between 1966 and 1976, on the phenomenon of immune deviation. Initially summarized are experiments with different forms of the flagellin antigen from Salmonella adelaide which established the inverse relationship between delayed‐type hypersensitivity (DTH) and antibody formation. Based on the flagellin studies, many of the key factors which determine whether an antigen will induce either DTH or antibody formation were delineated. These factors are just as relevant today as they were 25 years ago. Subsequent analyses at the cellular level demonstrated that different T cell subsets mediate DTH and T cell help and maintain immune deviation by suppressor mechanisms. A number of fundamental questions raised by this early work remain unanswered and are discussed. These include the nature of the primary signalling events which initiate immune deviation, the role of B cells in the deviating process and the mechanism by which CD8+ T cells suppress antibody production.
An in vivo mammary infusion model for tissue migration of leucocytes during inflammation
Authors: GREENHALGH CHRIS J , JACOBS HELEN J , MEEUSEN ELS NT
Published: June 2007

Infusion of LPS or nematode larvae into the mammary glands of sheep induces recruitment of neutrophils or eosinophils respectively. While neutrophil recruitment required only a single infusion of LPS, repeated infusions of parasite larvae were required to induce significant eosinophil migration into the lumen of the glands. Eosinophil recruitment was accompanied by a distinct population of lymphocytes consisting mainly of activated (MHC class II and CD25+) T cells. L‐selectin was expressed at reduced levels on both neutrophils and eosinophils collected from the mammary gland compared with cells present in the blood of the same sheep. In addition, VLA‐4 and β1‐integrin were down‐regulated or negative in mammary eosinophils compared with strong expression in the blood while neutrophils were negative for these markers in both mammary washes and blood. Eosinophils in blood and mammary glands were negative for MHC class II, CD25 and CD4. Mast cells and lymphocyte aggregates were present in the tissue of glands chronically stimulated with parasite larvae while eosinophils were only present if the gland had been recently stimulated.

These studies show that detailed in vivo analysis of leucocyte migration can be easily performed in the sheep mammary infusion model which allows non‐invasive and repeated sampling of inflammatory cells before and after tissue migration.
Molecular basis of immune evasion strategies by adenoviruses
Authors: HAYDER HIKMAT , MÜLLBACHER ARNO
Published: June 2007

Human adenoviruses have provided valuable insights into virus‐host interactions at the clinical and experimental levels. In addition to the medical importance of adenoviruses in acute infections and the ability of the virus to persist in the host, adenovirus‐based recombinants are being developed as potential vaccine vectors. It is now clear that adenoviruses employ various strategies to modulate the innate and the adaptive host immune defences. Adenovirus genome‐coded products that interact with the immune response of the host have been identified, and to a large extent the molecular mechanisms of their functions have been revealed. Such knowledge will no doubt influence our approach to the areas of viral pathogenesis, vaccine development and immune modulation for disease management.
Mechanisms of interference with the MHC class I‐restricted pathway of antigen presentation by herpesviruses
Authors: HILL ANN B
Published: June 2007

Herpesviruses are an ancient, ubiquitous family of DNA viruses, most of which share a lifestyle of latently or persistently infecting a young host, and spreading to infect a new host a generation later. Most herpesviruses interfere with antigen presentation via the MHC class I‐restricted pathway of antigen presentation, suggesting that impairment of the cytotoxic T lymphocyte response is necessary for the maintenance of this lifestyle. The diverse molecular mechanisms that have so far been discovered employed by Epstein‐Barr virus, herpes simplex viruses, and human and murine cytomegaloviruses are described in this review.
M‐T2: A poxvirus TNF receptor homologue with dual activities
Authors: SEDGER LISA , McFADDEN GRANT
Published: June 2007

Poxviruses are experts at manipulating and evading the host's immune response. They have acquired a number of open reading frames which specifically confer direct anti‐immune properties, either by mimicking cytokine receptors and growth factors or by disarming cytokine regulatory cascades. The Myxoma T2 protein (M‐T2), a TNF receptor homologue is secreted from virus infected cells and can bind TNF‐α with high affinity, and thereby inhibit TNF‐α‐mediated cytotoxicity. M‐T2 also acts to inhibit virus‐induced lymphocyte apoptosis by an as yet undefined mechanism. As such, T2 constitutes a significant virulence factor for poxviruses, influencing the outcome of infection, both in vitro and in vivo.
Antigenic variation and immune evasion in Plasmodium falciparum malaria
Authors: REEDER JOHN C , BROWN GRAHAM V
Published: June 2007

Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even in endemic regions, immunity to malaria builds slowly and is rarely complete. Strategies such as antigenic variation and antigenic diversity are critical to a parasite's ability to evade the host immune response and infect previously exposed individuals. In this short review, the phenomenon of antigenic variation is discussed in relation to immune evasion and its impact on parasite pathogenesis. Recent advances in the understanding of the underlying molecular mechanisms of antigenic variation are examined and questions posed for future research.
Inhibition of T cell mitogenesis by a novel anti‐CD45R monoclonal antibody
Authors: ROBSON SIMON C , SIEGEL JONATHAN B , KIRSCH RALPH E
Published: June 2007

CD45 consists of a major family of membrane glycoproteins which have protein tyrosine phosphatase activity and regulate early activation events, progression and maturation signals in leucocytes. Various isoforms of CD45 (Mr 180–240 kDa) regulate sets of intermolecular associations between different surface receptors, and appear to be differentially expressed on B and T cells (namely CD45RA, B or CD45RO). We describe a novel IgG2a mAb directed against restricted and unique CD45R modified epitopes expressed preferentially on peripheral blood T cells. This anti‐CD45R antibody (l(2)4c) at concentrations of 50 and 200 ng/mL inhibited mitogenic T cell lectin and anti‐CD3‐stimulated lymphocyte proliferation and blocked associated IL‐2 secretion in vitro. Phorbol ester‐stimulated mitogenesis was unaltered suggesting that the inhibition occurs independent of protein kinase C‐mediated pathways. Western blotting and immuno‐precipitation of purified cell lysates reveals that I(2)4c preferentially binds the higher Mr, bands of CD45 expressed on T cells. Following T cell activation in vitro, the 190 kDa band became more predominant and an additional 130 kDa protein, possibly a proteolytic fragment was recognized. I(2)4c may inhibit T cell mitogenesis by direct effects on CD45R alone or by preventing interaction with other membrane‐associated proteins and hence adhesive interactions with monocytes. Such interactions may however inhibit the initiation of signal transduction and., as a consequence, alter cellular activation by mitogenic lectins and anti‐CD3 in vitro.
Defence against the immune barrage: Helminth survival strategies
Authors: RIFFKIN MICHAEL , SEOW HENG‐FONG , JACKSON DAVID , BROWN LORENA , WOOD PAUL
Published: June 2007

Parasites have generated a range of countermeasures against the host immune system which allows their survival long enough for reproduction to occur. Parasite subsistence is enhanced by evasion of the immune response utilizing mechanisms such as antigenic variation of exposed immunogenic proteins, shedding of surface proteins which are the target of an immune response, and protease production to neutralise specific anti‐parasite immune components. Recent advances in the fields of immunology and parasitology have highlighted a range of mechanisms by which the parasite actively modulates the immune response to allow survival. Parasite factors can directly suppress the function of certain subsets of immune cells as well as stimulating other cell populations which have suppressive activity. Strategies such as the skewing of the type 1‐type 2 cytokine profile to that of a less appropriate response, and the mimicry of host immune regulatory proteins are becoming more widely acknowledged as means by which helminths enhance their survival. An illustration of the extent by which parasites can exploit host immune components is emphasized by the use of host cytokines as parasite growth factors. This review will examine some of the strategies developed by helminths which enables them not only to survive in the host, but also to prosper.
Fluctuating population dynamics promotes the evolution of phenotypic plasticity
Authors: Pineda-Krch Mario , Svanbäck Richard , Doebeli Michael
Published: June 2007

An increasing number of studies are showing evidence in support of sympatric speciation. One basic question remains, however. When a population has undergone a branching in its phenotype, is this due to an evolutionary branching in the underlying genotype or due to phenotypic plasticity modifying a single genotype? Thus, phenotypic plasticity has come to be viewed as a trait subject to selection, just like any other phenotypic character1,2. Here we present a model addressing the conditions under which a predator phenotype experiencing selection for two alternative optimal phenotypes gives rise to genetically based phenotypic branching or to phenotypic plasticity, allowing the corresponding genotype to give rise to two alternative, well-adapted phenotypes.
Inversion of chord-integrated data from noncircular tokamak plasmas (abstract)a)
Authors: Bravenec R. V. , Solano E. R. , Brower D. L. , Jiang Y.
Published: June 2007

The superior performance of diverted and elongated plasmas in tokamaks motivates improvements of inversion techniques for chord integrated data (from interferometry, spectroscopy, bolometry, etc.) from such noncircular plasmas. We present a technique planned for TEXT-U. First, flux-surface contours are calculated using EFIT or a filament code. A computer subroutine is provided which then computes, for a given chord, the length of the chord segment enclosed within the flux surface ψ, as a function of ψ from the tangent surface ψtan outward. Using the length functions, the inversions may be performed using the technique of Park or by least-squares fitting. Inversions of FIR interferometer data are presented.
1,3,5-trinitro-1,3,5-triazine decomposition and chemisorption on Al(111) surface: First-principles molecular dynamics study
Authors: Umezawa Naoto , Kalia Rajiv K. , Nakano Aiichiro , Vashista Priya , Shimojo Fuyuki
Published: June 2007

We have investigated the decomposition and chemisorption of a 1,3,5-trinitro-1,3,5-triazine (RDX) molecule on Al(111) surface using molecular dynamics simulations, in which interatomic forces are computed quantum mechanically in the framework of the density functional theory (DFT). The real-space DFT calculations are based on higher-order finite difference and norm-conserving pseudopotential methods. Strong attractive forces between oxygen and aluminum atoms break N–O and N–N bonds in the RDX and, subsequently, the dissociated oxygen atoms and NO molecules oxidize the Al surface. In addition to these Al surface-assisted decompositions, ring cleavage of the RDX molecule is also observed. These reactions occur spontaneously without potential barriers and result in the attachment of the rest of the RDX molecule to the surface. This opens up the possibility of coating Al nanoparticles with RDX molecules to avoid the detrimental effect of oxidation in high energy density material applications.
Analytical study of certain magnetohydrodynamic-α models
Authors: Linshiz Jasmine S. , Titi Edriss S.
Published: June 2007

In this paper we present an analytical study of a subgrid scale turbulence model of the three-dimensional magnetohydrodynamic (MHD) equations, inspired by the Navier-Stokes-α (also known as the viscous Camassa-Holm equations or the Lagrangian-averaged Navier-Stokes-α model). Specifically, we show the global well-posedness and regularity of solutions of a certain MHD-α model (which is a particular case of the Lagrangian averaged magnetohydrodynamic-α model without enhancing the viscosity for the magnetic field). We also introduce other subgrid scale turbulence models, inspired by the Leray-α and the modified Leray-α models of turbulence. Finally, we discuss the relation of the MHD-α model to the MHD equations by proving a convergence theorem, that is, as the length scale α tends to zero, a subsequence of solutions of the MHD-α equations converges to a certain solution (a Leray-Hopf solution) of the three-dimensional MHD equations.
Inviscid dyadic model of turbulence: The fixed point and Onsager’s conjecture
Authors: Cheskidov Alexey , Friedlander Susan , Pavlović Nataša
Published: June 2007

Properties of an infinite system of nonlinearly coupled ordinary differential equations are discussed. This system models some properties present in the equations of motion for an inviscid fluid such as the skew symmetry and the three-dimensional scaling of the quadratic nonlinearity. It is proved that the system with forcing has a unique equilibrium and that every solution blows up in finite time in H5∕6 norm. Onsager’s [Nuovo Cimento 6, 279–287 (1949)] conjecture is confirmed for the model system.
Copper selenide nanowires and nanocrystallites in alumina: Carrier relaxation, recombination, and trapping
Authors: Statkutė G. , Tomašiūnas R. , Jagminas A.
Published: June 2007

Nonequilibrium carrier dynamics in copper selenide (Cu2−δSe δ=0.15, Cu3Se2) nanowires (diameter ≈18 nm, height ≈2 μm) and nanocrystallites (diameter≈18 nm) in femto- and picosecond time domains by the means of a transient dynamic grating technique were investigated. Bulk and quantum confinement approaches were used to fit the experimental results using nonequilibrium carrier fast relaxation, recombination, and trapping mechanisms. A nonradiative Auger recombination was concluded to be the main mechanism of nonequilibrium carrier recombination. The Auger coefficient for copper selenide was estimated of the order of 10−30−10−29 cm6 s−1. Hole trapping at shallow impurity centers in nanowires was interpreted. From calculating the experimental results the trapping parameters and high concentration of centers >1020 cm−3 were evaluated. Finally, direct measurement of carrier lifetime in copper selenide nanostructures showed values of the order of ≈10−10 s. Samples were characterized by the means of transmission electron microscopy, scanning electron microscopy, x-ray diffraction, and optical spectroscopy.
Preferential hydration of lysozyme in water/glycerol mixtures: A small-angle neutron scattering study
Authors: Sinibaldi Raffaele , Ortore Maria Grazia , Spinozzi Francesco , Carsughi Flavio , Frielinghaus Henrich , Cinelli Stefania , Onori Giuseppe , Mariani Paolo
Published: June 2007

In solution small-angle neutron scattering has been used to study the solvation properties of lysozyme dissolved in water/glycerol mixtures. To detect the characteristics of the protein-solvent interface, 35 different experimental conditions (i.e., protein concentration, water/glycerol fraction in the solvent, content of deuterated compounds) have been considered and a suitable software has been developed to fit simultaneously the whole set of scattering data. The average composition of the solvent in the close vicinity of the protein surface at each experimental condition has been derived. In all the investigated conditions, glycerol resulted especially excluded from the protein surface, confirming that lysozyme is preferentially hydrated. By considering a thermodynamic hydration model based on an equilibrium exchange between water and glycerol from the solvation layer to the bulk, the preferential binding coefficient and the excess solvation number have been estimated. Results were compared with data previously derived for ribonuclease A in the same mixed solvent: even if the investigated solvent compositions were very different, the agreement between data is noticeable, suggesting that a unique mechanism presides over the preferential hydration process. Moreover, the curve describing the excess solvation number as a function of the solvent composition shows the occurrence of a region of maximal hydration, which probably accounts for the changes in protein stability detected in the presence of cosolvents.
Exciton self-trapping in tetrafluoro-dimethyl-aminoacridine single crystals
Authors: Tavazzi S. , Miozzo L. , Papagni A. , Raimondo L. , Silvestri L. , Spearman P. , Camposeo A. , Polo M. , Pisignano D.
Published: June 2007

The UV-visible optical spectra of 1,2,3,4-tetrafluoro-7-(N,N)dimethyl-amino-acridine single crystals are reported. The results are discussed on the basis of the molecular transitions and crystal packing in the framework of the theory of molecular excitons under a fluctuating potential field due to dynamic disorder. A strong local geometry distortion is demonstrated by applying the Urbach rule to the absorption tails, which is the amplitude of the local potential fluctuation being larger than the intermolecular transfer energy. The lineshape and linewidth of the emission band and its temperature dependence give further evidence of exciton self-trapping.
Absorption intensities and emission cross section of intermanifold transition of Er3+ in Er3+:Y2O3 nanocrystals
Authors: Sardar Dhiraj K. , Nash Kelly L. , Yow Raylon M. , Gruber John B.
Published: June 2007

The room temperature absorption intensities of Er3+(4f11) transitions in synthesized Er3+:Y2O3 nanocrystals have been analyzed using the Judd-Ofelt (J-O) model in order to obtain the phenomenological intensity parameters. The J-O intensity parameters are subsequently used to determine the radiative decay rates, radiative lifetimes, and branching ratios of the Er3+ transitions from the upper multiplet manifolds to the corresponding lower-lying multiplet manifolds LJ2S+1 of Er3+(4f11). The emission cross section of the important intermanifold Er3+ I13∕24→I15∕24 (1.5μm) transition has been determined. The room temperature fluorescence lifetime of this transition in Er3+:Y2O3 nanocrystals was measured. From the radiative lifetime determined from the J-O model and measured fluorescence lifetime, the quantum efficiency of this material was determined. The comparative study of Er3+(4f11) ions suggests that synthesized Er3+:Y2O3 nanocrystals could be an excellent alternative to single crystal Er3+:Y2O3 for certain applications especially in the near infrared region.
Effect of the surface charge discretization on electric double layers: A Monte Carlo simulation study
Authors: Madurga Sergio , Martín-Molina Alberto , Vilaseca Eudald , Mas Francesc , Quesada-Pérez Manuel
Published: June 2007

The structure of the electric double layer in contact with discrete and continuously charged planar surfaces is studied within the framework of the primitive model through Monte Carlo simulations. Three different discretization models are considered together with the case of uniform distribution. The effect of discreteness is analyzed in terms of charge density profiles. For point surface groups, a complete equivalence with the situation of uniformly distributed charge is found if profiles are exclusively analyzed as a function of the distance to the charged surface. However, some differences are observed moving parallel to the surface. Significant discrepancies with approaches that do not account for discreteness are reported if charge sites of finite size placed on the surface are considered.
Quantum similarity study of atoms: A bridge between hardness and similarity indices
Authors: Borgoo A. , Torrent-Sucarrat M. , De Proft F. , Geerlings P.
Published: June 2007

A hardness based similarity index for studying the quantum similarity for atoms is analyzed. The investigation of hardness and Fukui functions of atoms leads to the construction of a quantum similarity measure, which can be interpreted as a quantified comparison of chemical reactivity of atoms. Evaluation of the new measure reveals periodic tendencies throughout Mendeleev’s table. Moreover on the diagonal the global hardness was recovered. Considering a corresponding quantum similarity index reveals that renormalization of the measure can mask periodic patterns. The hardness was calculated for atoms with nuclear charge 3⩽Z⩽103, using the best single configuration electron density functions available. Different hardness kernels were used and the importance of the different contributions to the kernel was investigated. The atomic self-similarities constructed in this way show a fair correlation with experimental atomic polarizability.
Numerical simulation for the formation of nanostructures on the Stranski–Krastanow systems by surface undulation
Authors: Chiu C.-H. , Huang Z.
Published: June 2007

The nanostructure formation of the Stranski–Krastanow (SK) systems is investigated by simulating the surface undulation of the systems driven by the surface diffusion mechanism. Of particular interest is how the surface undulation leads to the development of faceted nanostructures and wetting layers. The results reveal that the development exhibits three common features in the coarsening SK systems, while the development also results in distinct film morphologies, controlled by the maximum surface coverage of faceted islands. The maximum surface coverage depends on the film thickness, the ratio between the two characteristic lengths of the SK system, and the effective surface energy density of flat film.
Photoluminescence from InAsN quantum dots embedded in GaInNAs/GaAs quantum wells
Authors: Motyka M. , Kudrawiec R. , Sęk G. , Misiewicz J. , Bisping D. , Marquardt B. , Forchel A. , Fischer M.
Published: June 2007

Photoluminescence (PL) from InAsN quantum dots embedded in a GaInNAs/GaAs quantum well (QW) has been investigated at low excitation conditions in the temperature range of 15–305 K. A very efficient emission at 1.3 μm with a small spectral broadening (30 meV) has been observed at room temperature for this system. The emission intensity decreases by only two decades in the whole investigated temperature range. Carrier escape into the states of the surrounding QW has been recognized as the main PL thermal quenching mechanism and the possible quenching via defect states has appeared to be negligible in this regime of excitation.
Contrast and resolution versus specimen thickness in low energy scanning transmission electron microscopy
Authors: Morandi Vittorio , Merli Pier Giorgio
Published: June 2007

A theoretical and experimental investigation of contrast and resolution versus specimen thickness in scanning transmission electron microscopy at low energy is reported. Due to absence of postspecimen imaging lenses it is possible to have images with a resolution defined by the probe size using very wide collection angles and independent of the energy loss of the transmitted electrons. The fundamental limitation in observable specimen thickness is represented by the signal to noise ratio, i.e., the intensity of the beam current. The investigated specimens are semiconductor multilayers and Sb precipitates in a Si implanted specimen. The observations of layers crossing the whole specimens parallel to the electron beam point out that only a small portion of them, the one close to the surface, causes the image contrast, while the portion below, where the probe diameter, as a consequence of the broadening, is larger than the layer itself, reduces the contrast. A similarity with recent results, achieved in scanning transmission electron microscopy at high energy, where the layers are represented by atomic columns, is pointed out. The image contrast depends on the angular distribution of the transmitted electrons, and for thick specimens it is always of bright field type, independent of the collection angle of the transmitted electrons. The observation of Sb precipitates, distributed along the specimen thickness, evidences the role of beam broadening on the resolution and contrast.