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Immunotherapy of cancer utilizes dendritic cells (DCs) for antigen presentation and the induction of tumor-specific immune responses. However, the therapeutic induction of anti-tumor immunity is limited by tumor escape mechanisms. In this study, immortalized dendritic D2SC/1 cells were transduced with a mutated version of the p53 tumor suppressor gene, p53M234I, or p53C132F/E168G, which are overexpressed in MethA fibrosarcoma tumor cells. In addition, D2SC/1 cells were fused with MethA tumor cells to generate a vaccine that potentially expresses a large repertoire of tumor-antigens. Cellular vaccines were transplanted onto Balb/c mice and MethA tumor growth and anti-tumor immune responses were examined in vaccinated animals. D2SC/1-p53M234I and D2SC/1-p53C132F/E168G cells induced strong therapeutic and protective MethA tumor immunity upon transplantation in Balb/c mice. However, in a fraction of immunized mice MethA tumor growth resumed after an extended latency period. Analysis of these tumors indicated loss of p53 expression. Mice, pre-treated with fusion hybrids generated from D2SC/1 and MethA tumor cells, suppressed MethA tumor growth and averted adaptive immune escape. Polyclonal B-cell responses directed against various MethA tumor proteins could be detected in the sera of D2SC/1-MethA inoculated mice. Athymic nude mice and Balb/c mice depleted of CD4(+) or CD8(+) T-cells were not protected against MethA tumor cell growth after immunization with D2SC/1-MethA hybrids. Our results highlight a potential drawback of cancer immunotherapy by demonstrating that the induction of a specific anti-tumor response favors the acquisition of tumor phenotypes promoting immune evasion. In contrast, the application of DC/tumor cell fusion hybrids prevents adaptive immune escape by a T-cell dependent mechanism and provides a simple strategy for personalized anti-cancer treatment without the need of selectively priming the host immune system.
BACKGROUND: Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage.
METHODS: In cardiosurgical patients with cardiopulmonary bypass (CPB) RIPC was induced by four 5 minute cycles of upper limb ischemia/reperfusion. Cardiac tissue was obtained before as well as after CPB and serum cTnT concentrations were measured. Tissue derived from control patients (N = 17) with high cTnT concentrations (≥0.32 ng/ml) and RIPC patients (N = 18) with low cTnT (≤0.32 ng/ml) was subjected to gelatin zymography to quantify MMP-2/9 activities.
RESULTS: In cardiac biopsies obtained before CPB, activities of MMP-2/9 were attenuated in the RIPC group (MMP-2: Control, 1.13 ± 0.13 a.u.; RIPC, 0.71 ± 0.12 a.u.; P < 0.05. MMP-9: Control, 1.50 ± 0.16 a.u.; RIPC, 0.87 ± 0.14 a.u.; P < 0.01), while activities of the pro-MMPs were not altered (P > 0.05). In cardiac biopsies taken after CPB activities of pro- and active MMP-2/9 were not different between the groups (P > 0.05). Spearman's rank tests showed that MMP-2/9 activities in cardiac tissue obtained before CPB were positively correlated with postoperative cTnT serum levels (MMP-2, P = 0.016; MMP-9, P = 0.015).
CONCLUSIONS: Activities of MMP-2/9 in cardiac tissue obtained before CPB are attenuated by RIPC and are positively correlated with serum concentrations of cTnT. MMPs may represent potential targets for RIPC mediated cardioprotection.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00877305.
Acacia pendula, Weeping Myall, (family Fabaceae) is the most legislatively protected plant species in the New South Wales Hunter Valley. Under the NSW Threatened Species Conservation Act 1995 it is listed as an Endangered Population (in the Hunter Valley) and as a component of two Endangered Ecological Communities (one in the Hunter, one elsewhere in NSW); it is also listed as a Critically Endangered Ecological Community (in the Hunter Valley) on the Commonwealth Environment Protection and Biodiversity Conservation Act 1999 and listed as threatened in three other eastern Australian States.
To ascertain the likely original distribution of stands of Acacia pendula in the Hunter Valley, this paper examines the writings of early Australian explorers, herbarium and database records, and the species habitat attributes across NSW. None of the journals examined, including those of botanist/explorer Allan Cunningham (who originally collected Acacia pendula from the Lachlan River in 1817), Thomas Mitchell or Ludwig Leichhardt, make note of the species for the Hunter Valley. Several explorers do, however, record Acacia pendula regularly (>100 times) across other parts of NSW, Queensland, and South Australia.
Historical herbarium and database records show a paucity of records from the Hunter prior to the year 2000, after which a 37-fold increase in observations since 1951 is apparent. For the first 128 years of botanical exploration (1823 to 1951), there are no validated collections or records of Acacia pendula from the Hunter Valley. The single exception is a specimen collected by Cunningham from 1825 (lodged at Kew, UK), purported to be from ‘Hunters River’, but which is morphologically different to other collections of Acacia pendula from that time. There is some uncertainty over the origins of this specimen.
Analysis of habitats supporting Acacia pendula in NSW outside of the Hunter show them to differ significantly in geological age, soil type, rainfall and elevation from those in the Hunter.
Collectively, these findings provide a strong circumstantial case that Acacia pendula was absent from the Hunter at the time of European settlement; this has important implications for the conservation and management of Hunter stands. Rather than being a threatened species in the Hunter Valley, it is postulated that Acacia pendula has been intentionally and/or accidentally introduced to the region, and may now be imposing a new and emerging threat to the endangered grassy woodlands and forests there. There is now an urgent need for genetic studies to clarify the origins of the current Hunter Valley stands, and to define the taxonomic limits of Acacia pendula and its close relatives.
Este artigo recapitula as traduções de Wilhelm Busch publicadas no Brasil e aponta que determinadas circunstâncias de publicação levaram a uma recepção unilateral de sua obra exclusivamente como literatura infantil nesse país. Entre outras estratégias que poderiam estender para uma faixa etária adulta o público leitor da poesia humorística buschiana, propõe-se que o Knittelvers seja traduzido para o português como decassílabo iâmbico. Uma tradução anotada do poema "Hänsel und Gretel" nesse padrão métrico-acentual testa em que medida a escolha consciente de um ritmo e o aproveitamento de associações culturais desencadeadas por ele podem destacar o efeito irônico desse pseudoconto-de-fada.
Based on a meta-analysis, Redick and Lindsey (2013) found that complex span and n-back tasks show an average correlation of r = 0.20, and concluded that "complex span and n-back tasks cannot be used interchangeably as working memory measures in research applications" (p. 1102). Here, we comment on this conclusion from a psychometric perspective. In addition to construct variance, performance on a test contains measurement error, task-specific variance, and paradigm-specific variance. Hence, low correlations among dissimilar indicators do not provide strong evidence for the existence, or absence, of a construct common to both indicators. One way to arrive at such evidence is to fit hierarchical latent factors that model task-specific, paradigm-specific, and construct variance. We report analyses for 101 younger and 103 older adults who worked on nine different working memory tasks. The data are consistent with a hierarchical model of working memory, according to which both complex span and n-back tasks are valid indicators of working memory. The working memory factor predicts 71% of the variance in a factor of reasoning among younger adults (83% for among older adults). When the working memory factor was restricted to any possible triplet of working memory tasks, the correlation between working memory and reasoning was inversely related to the average magnitude of the correlations among the indicators, indicating that more highly intercorrelated indicators may provide poorer coverage of the construct space. We stress the need to go beyond specific tasks and paradigms when studying higher-order cognitive constructs, such as working memory.
CD4+CD25+ regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of the CD4 molecule that is not recognized by other anti-CD4 mAbs. We found that, due to this special epitope binding, BT-061 induces a unique phosphorylation of T-cell receptor complex-associated signaling molecules. This is sufficient to activate the function of Tregs without activating effector T cells. Furthermore, BT-061 does not induce the release of pro-inflammatory cytokines. These results demonstrate that BT-061 stimulation via the CD4 receptor is able to induce T-cell receptor-independent activation of Tregs. Selective activation of Tregs via CD4 is a promising approach for the treatment of autoimmune diseases where insufficient Treg activity has been described. Clinical investigation of this new approach is currently ongoing.
We explore the parameter space of the two-flavor thermal quark–meson model and its Polyakov loop-extended version under the influence of a constant external magnetic field B. We investigate the behavior of the pseudo critical temperature for chiral symmetry breaking taking into account the likely dependence of two parameters on the magnetic field: the Yukawa quark–meson coupling and the parameter T0 of the Polyakov loop potential. Under the constraints that magnetic catalysis is realized at zero temperature and the chiral transition at B=0 is a crossover, we find that the quark–meson model leads to thermal magnetic catalysis for the whole allowed parameter space, in contrast to the present picture stemming from lattice QCD.
Orientation: Publishing methodologically sound, empirically based studies in reputable accredited scientific journals are essential in order to advance knowledge and evidence-based practice in the field of industrial and organisational psychology.
Research purpose: The purpose of the research was to conduct a broad content analysis of the articles published in the South African Journal of Industrial Psychology (SAJIP) between 2004 and 2013. The study aimed to provide a descriptive overview of the most frequent content themes,published authors and institutions, research approaches, strategies, designs and analysis techniques, software packages and sample sizes in industrial and organisational (I-O) psychology utilised in the publications.
Motivation for study: The periodic analyses of published content in scholarly journals provide an index of the extent to which the publications reflect the scope of practice in a given discipline and broaden insight into the direction and relevance of research published in a journal.
Research design, approach and method: A broad systematic content analysis was conducted of 342 documented articles published in the SAJIP between 2004 and 2013. Descriptive data(frequencies and percentages) were used to report the findings.
Main findings: The publishing pattern of the SAJIP appeared to correspond with its focus and scope. Manuscripts utilising mostly cross-sectional quantitative correlational research designs with large samples (n > 201) were published in the SAJIP. The University of Johannesburg and Professor Sebastiaan (Ian) Rothmann were the largest contributors to publications between 2004 and 2013. Organisational psychology and psychometrics were the most prominent domains in I-O psychology research. Data were predominantly processed utilising SPSS.
Practical implications: The insights derived from the findings can be employed to plan future research initiatives in the field of I-O psychology.
Contribution/value-add: The findings provide valuable insight into the current status of the foci of I-O psychology research as published in the SAJIP between 2004 and 2013 and the contribution made by the SAJIP to advancing knowledge and evidence-based practice in I-O psychology.
O trabalho pretende discutir o duplo caráter das obras de arte a partir da obra de Theodor W. Adorno. Pretende-se examinar os argumentos sustentados pelo autor sobre o caráter social das obras, principalmente, no caso da música, em que se pode percebercomo o desenvolvimento do próprio material musical expressa as aporias encontradas na sociedade. Por meio de uma crítica dialética, modo pelo qual as obras de arte respondem às contradições da sociedade, colocando-se, assim, como força de resistência à reificação, quanto a influência negativa que sofrem, porexemplo, no contexto da indústria cultural. Além disso, o artigo pretende se dedicar à reflexão sobre a autonomia das obras de arte, qualidade que as mantém fechadas, desenvolvendo-se apenas segundo leis formais internas, sem que atendam a uma função social. É nesse sentido quese coloca a exigência de uma determinada forma de recepção dasobras, orientada não pela fruição, mas pela possibilidade de interpretar seu teor de verdade. Assim, a dialética presente no modo como as obras se relacionam com a sociedade torna possível concebê-las como possibilidade de crítica à realidade e de resistência à reificação.
The ground beetle genus Cymindis is the most species rich amongst genera in the carabid subtribe Cymindidina (tribe Lebiini). Four subgenera are often recognized, i.e. Cymindis (sensu stricto) Latreille, Afrotarus Jeannel, Taridius Chaudoir and Pinacodera Schaum. Cymindis (sensu stricto) has a predominately Holarctic distribution (Hunting 2013) and includes Cymindis alutacea Wollaston, C. dohrnii Wollaston and C. anchomenoides Wollaston (the last one sometimes placed in Tarulus Bedel, either ranked as a genus or a subgenus), all three endemic to the Cape Verde Islands (Geisthardt 1988, 1996).