1,720,999 research outputs found
Bone seeking matrix metalloproteinase-2 inhibitors prevent bone metastatic breast cancer growth
Full text linkBone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorβ (TGFβ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed. Therefore, to overcome potential toxicities noted with previous broad-spectrum MMP inhibitors (MMPIs), we used highly selective bisphosphonic based MMP-2 inhibitors (BMMPIs) that allowed for specific bone targeting. In vitro, BMMPIs impacted the viability of breast cancer cell lines and osteoclast precursors but not osteoblasts. In vivo, we demonstrated using two bone metastatic models (PyMT-R221A and 4T1) that BMMPI treatment significantly reduced tumor growth and tumor associated bone destruction. Additionally, BMMPIs are superior in promoting tumor apoptosis compared to the standard of care bisphosphonate, zoledronate. We demonstrated MMP-2 selective inhibition in the bone microenvironment using specific and broad spectrum MMP probes. Further, compared to zoledronate, BMMPI treated mice had significantly lower levels of TGFβ signaling and MMP generated type I collagen carboxy-terminal (ICTP) fragments. Taken together, our data show the feasibility of selective inhibition of MMPs in the bone metastatic breast cancer microenvironment. We posit that BMMPIs could be easily translated to the clinical setting for the treatment of bone metastases given the well-tolerated nature of bisphosphonates
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Molecular characterization of CD4 homologue in Brown Trout (Salmo trutta)
No full textPhD Arbeit - Veterinärmedizinische Universität Wien - 2021
Aus rechtlichen Gründen sind nicht alle Teile dieser Arbeit frei zugänglich. Der Zugriff auf den elektronischen Volltext ist auf Angehörige der Veterinärmedizinischen Universität Wien beschränkt. Bitte einloggen!Seit dem Aufkommen neuer Infektionskrankheiten, die eine enorme finanzielle Bedrohung für die Fischaquakultur darstellen, war die Forschung zu Fragen der Fischgesundheit in den letzten zehn Jahren von Bedeutung. Insbesondere der immunologische Aspekt wird als eines der wichtigsten Forschungsgebiete für das Verständnis des Fortschreitens der Krankheit angesehen. Diese Studie wurde entwickelt, um CD4 T-Zellen der Bachforellen zu charakterisieren. Polyklonale Antikörper gegen CD4 Moleküle wurden eingesetzt um den Einfluss der CD4+ Zellen bei der viralen hämorrhagischen Septikämie (VHS) zu untersuchen. Darüber hinaus wurde die Expression der CD4 mRNA untersucht, um ein umfassenderes Bild der Immunantwort bei Bachforellen gegen VHS-Viren zu erhalten. Es konnten drei Gene CD4-1, CD4-2a und CD4-2b identifiziert werden, die mittels einer Homologieklonierung kloniert und weiter charakterisiert wurden. Die erste cDNA von CD4-1 enthielt vier Immunglobulin- Superfamilien-ähnliche Domänen und war 1473 Nukleotide lang, wobei ein offener Leserahmen (ORF) für 490 Aminosäuren codierte. Das CD4-2-Gen schien dupliziert zu sein und die Varianten heißen CD4-2a und CD4-2b. CD-2a und CD4-2b waren 945 und 999 Nukleotide lang mit 2 Immunglobulin-Superfamilien-ähnlichen Domänen und enthielten ORFs mit 313 bzw. 331 Aminosäuren. Alle CD4-Gene von Bachforellen zeigten mit dem Säuger- CD4 vergleichbare Eigenschaften: Sie enthielten extrazelluläre immunglobulin-ähnliche Domänen sowie zytoplasmatische Domänen (Lck) und Aktivierungsmotive auf Tyrosinbasis. Obwohl die Sequenzidentitäten zu Säugetieren gering waren (13-15%), sind sie homolog zu den Säuger-CD4, dies gilt auch für andere veröffentlichte Salmonidensequenzen. Die übersetzte CD4-1-Proteinsequenz für Bachforellen weist eine Identität von 95% und 89% mit Atlantischem Lachs und Regenbogenforellen auf. Während CD4-2a- und CD4-2b- Proteinsequenzen eine Identität von 84% und 97,7% mit Regenbogenforellen bzw. Atlantischem Lachs aufweisen. Die basalen Expressionsniveaus von CD4-mRNA waren am höchsten im Thymus, gefolgt von Kopfniere und Milz. Eine geringere Expression des T-Zell-Markers wurde jedoch in Kiemen-, Leber-, Darm-, Herz- und Hirngewebe unter Verwendung von TaqMan-Assays und RT-qPCR beobachtet. Die begrenzte Verfügbarkeit spezifischer Antikörper gegen T-Zell spezifische Antigen von Bachforellen hatte die zellulären Immunantwortstudien jeglicher Art eingeschränkt. Diese Arbeit zeigte nun die Produktion eines polyklonalen Antikörpers gegen CD4-1 von Bachforellen und dessen Verwendung zur positiven Isolierung von Teilpopulationen von Leukozyten. Die Studie wurde durchgeführt, um die Proliferation von CD4+ -Zellen in verschiedenen Geweben während einer VHSV-Infektion unter Verwendung der Durchflusszytometrie zu untersuchen. Immunfluoreszenzfärbung und RT-PCR-Analyse validierten diesen Antikörper gegen CD4-1-Lymphozyten. Die Expression von CD4+ -Zellen in lymphoiden Organen und im Darm erhöhte sich in der infizierten Gruppe signifikant gegenüber der nicht infizierten Gruppe an bestimmten Tagen nach der Infektion (dpi). Die Ergebnisse legen nahe, dass die CD4+ T-Zellenbei dieser Virusinfektion eine wichtige Rolle spielen. Dieser Umstand ist mit der Rolle von CD4 positiven Zellen bei höheren Wirbeltieren vergleichbar. Darüber hinaus kann eine höhere Expression von CD4+ -Zellen in Bachforellen während einer VHVS-Infektion zur Resistenz gegen das Virus beitragen. Diese Ergebnisse sprechen auch dafür, dass dieser polyklonale Antikörper in anderen immunologischen Experimenten sowie zur Überwachung der Gesundheit und des Immunstatus von Bachforellen verwendet werden kann.PhD thesis - University of Veterinary Medicine Vienna - 2021
The full text is only available to university members. Please log in!Since the advent of new infectious diseases, which pose, a huge financial threat to the fish aquaculture industry, the research on fish health issues has been substantial during the last decade. The Immunological aspect is in particularly being considered as one of the vital derivatives in understanding the disease advancement. This study was designed to first characterize and then investigate the facilitating functions of brown trout T-cell marker; CD4, in protectiveness against the Viral Hemorrhagic Septicemia Virus (VHSV) after production of polyclonal antibodies to screen CD4+ cells in some of the cellular functional studies. Moreover, expression assays were also included to have a bigger picture of the immune response in brown trout against the virus. There were three genes CD4-1, CD4-2a, and CD4- 2b, cloned and characterized in brown Trout. The first cDNA of CD4-1 contained four immunoglobulin superfamily-like domains and was 1473 nucleotides long, with an open reading frame (ORF) encoding 490 amino acids. The CD4-2 gene appeared to be duplicated and the variants are named CD4-2a and CD4-2b that were 945 and 999 nucleotides long with 2 immunoglobulin superfamily-like domains and containing ORFs with 313 and 331 amino acids, respectively. All CD4 genes of brown trout demonstrated comparable characteristics with mammalian CD4: containing extracellular immunoglobulin-like domains as well as cytoplasmic domains (Lck), tyrosine-based activation motifs. In spite the sequence identities to mammals were low (13- 15%) they are homologous to mammalian CD4, this is also true for other published salmonids sequences. The translated brown trout CD4-1 protein sequence has a 95% and 89% identity with Atlantic salmon and rainbow trout, respectively. While CD4-2a and CD4-2b protein sequences share 84% and 97.7% identity with rainbow trout and Atlantic salmon, respectively. The basal expression levels of CD4-genes were studied and found to be highest in the thymus followed by the head kidney and spleen. However, comparably lower expression of T-cell marker was observed in gills, liver, intestine, heart, and brain tissues using RT-qPCR assays. The limited availability of specific antibodies against T-cell markers of brown trout had restricted the cellular immune response studies of any kind. This study demonstrated the production of a polyclonal antibody against CD4-1 of brown trout, for the positive isolation of sub-populations of leukocytes. The study was conducted to investigate the proliferation of CD4+ cells in different tissues during VHSV infection by using the flow cytometry technique. Immunofluorescence staining and RT-PCR analysis validated this antibody against CD4-1 lymphocytes. The CD4+ surface cell expression in lymphoid organs and intestine augmented in the infected group significantly than the non-infected group at specific days post-infection (dpi). The results suggest that the T-helper cells are important against VHSV, which is comparable to a higher vertebrate. Furthermore, higher expression of CD4+ cells in brown trout during VHVS infection may explain the resistance of brown trout to VHSV. These findings also advocate that this polyclonal antibody can be utilized in other immunological experiments as well as for monitoring the health, immune status of brown trout
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Description, molecular identification and pathological lesions of Huffmanela persica sp. nov. (Nematoda: Trichosomoididae: Huffmanelinae) from the daggertooth pike conger Muraenesox cinereus
No full textBackground: The genus Huffmanela Moravec, 1987 (Nematoda, Trichosomoididae, Huffmanelinae), represents a group of nematodes that infect both marine and freshwater fish, and the main gross feature of infection with different species of the genus is the presence of noticeable dark spots or tracks within the parasitized tissues. The purpose of this study was to describe morphologically and morphometrically the eggs of a new marine species of Huffmanela (Huffmanela persica sp. nov.), which was found in the form of black spots in the ovary and the tunica serosa of the stomach of the daggertooth pike conger (Muraenesox cinereus). The new species differs from Huffmanela hamo, another species reported from musculature of this host in Japan, in egg metrics, eggshell features and targeted organ. Molecular identification and pathological examination of the lesions caused by the new species are also reported.
Methods: Nematode eggs with varying degrees of development were separated from the infected tissues (ovary and tunica serosa of stomach) and investigated using light and scanning electron microscopy. Different species-specific markers (small subunit ribosomal DNA, 18S; large subunit ribosomal DNA, 28S; internal transcribed spacer, ITS) were used for molecular identification and phylogenetic study of the new species. Infected tissues were fixed in buffered formalin for pathological investigations.
Results: The fully developed eggs of H. persica sp. nov. are distinguished from those previously described from this host on the basis of their measurements (size, 54-68 × 31-43 µm; polar plugs, 6.4-9.7 × 8.4-12 µm; shell thickness, 3.5-6.1 µm) and a delicate but ornate uterine layer (UL) covering the entire eggshell including the polar plugs. Histopathological examination revealed a fibro-granulomatous inflammation in the ovary and the serosal layer of the stomach of infected fish. Maximum-likelihood (ML) phylogenetic analysis recovered a sister relationship between the new species of marine origin and Huffmanela species previously collected from freshwater hosts.
Conclusions: The present study is the first to report the molecular characterization and phylogenetic position of a teleost-associated marine species of the genus Huffmanela. A comprehensive list of nominal and innominate populations of Huffmanela is also provided.University of Veterinary Medicine, Vienna, Austri
- …
