1,721,068 research outputs found
What comes next in glycobiology
No full textGlycans, with their variable compositions and highly dynamic conformations, vastly expand the heterogeneity of whatever factor or cell they are attached to. These properties make them crucial contributors to biological function and organismal health and also very difficult to study. That may be changing as we look to the future of glycobiology.Fil: Seeberger, Peter H.. Max Planck Institute Of Biochemistry.; AlemaniaFil: Ge, Yun. Shenzhen Bay Laboratory; ChinaFil: Szymanski, Christine M.. University of Georgia; Estados UnidosFil: Kolarich, Daniel. Griffith University. Griffith School Of Engineering; AustraliaFil: Thaysen Andersen, Morten. Nagoya University; JapónFil: Packer, Nicolle H.. Mcquarie University; AustraliaFil: Fadda, Elisa. University of Southampton; Reino UnidoFil: Davis, Benjamin. University of Oxford; Reino UnidoFil: Nishihara, Shoko. Soka University; JapónFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Kwong, Peter D.. National Institutes of Health; Estados Unidos. Columbia University; Estados UnidosFil: Strasser, Richard. University Of Natural Resources And Life Sciences
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
Understanding vertebrate-pathogen co-evolution using state-of-the-art glycomics
No full textGlycosylation is important for cellular function, homeostasis, and sustenance of species. There is enough evidence to prove that glycans are at the crossroads of species-specific evolution and host pathogen co-evolution. Loss of Nglycolylneuraminic acid (NeuGc) in humans, New World monkeys, certain bats and other vertebrates, or loss of alpha Galactose [...] epitopes only in hominids and Old-World monkeys are just two examples for significant glycan based evolutionary events. On the other hand, pandemics such as Influenza, SARS-CoV-1, MERS-CoV and SARS-CoV-2 have emerged from animal hosts (such as wild birds or bats) that are genetically distant to humans. A pathogen with zoonotic and possible pandemic potential must cross a lot of barriers such as interspecies spill over or effective transmission before it starts to rapidly infect humans. "Phyloglycomics" refers to the understanding of the evolutionary relationship of species-specific glycosylation by systematically curating species and tissue/body fluid specific glycomes. During my PhD I have established a platform to evaluate and understand vertebrate glycans, which are the products of glycosyltransferases/glycosidases. Phyloglycomics seeks to understand the speciesspecific glycan features, which are represent the concerted activity of glycosyltransferases and glycosidases. Such a knowledge base is crucial in our quest to begin to understand the complex network of host-pathogen coevolution and infection patterns that undoubtedly contributes to the ability of zoonotic diseases to evolve and cross species boundaries. [...]Thesis (PhD Doctorate)Doctor of Philosophy (PhD)Institute for GlycomicsFull Tex
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
The importance of glycosylation in Acute Lymphoblastic Leukemia
No full textAcute leukemias, such as acute lymphoblastic leukemia (ALL), are aggressive cancers characterized by the rapid proliferation of malignant hematopoietic cells. Throughout the last 60 years, childhood ALL’s long-term survival rates increased from less than 10% to more than 90%. Despite these improvements, certain subtypes remain hard to manage (e.g. mixed lineage leukemia, MLL-r), and even new therapies frequently fail. Therefore, identifying leukemia-cell restricted antigens in these ALL subtypes remains crucial in the quest to develop novel diagnostic tools and specific treatments. Traditionally, ALL research has mostly been focusing on genomics and transcriptomics efforts, mainly due to the limited amounts of patient material, and technical difficulties throughout sample processing. The potential encompassed in the use of other -omics technologies has remained unexplored in the context of ALL. For the work presented in this thesis, I have focused on undertaking the first comprehensive characterisation of glycocalyx alterations that occur in ALL and particularly in MLL-r in primary, patient derived cancer cells. This work supports the concept that the glycocalyx of ALL and MLL-r cells undergoes dramatic alterations that clearly differentiate these cells from healthy precursor B- (pre-B) cells. These findings might open doors towards novel potential diagnostic and therapeutic targets. The studies encompassed in chapters III, IV and V were performed in collaboration with Prof. Eleonora Heisterkamp’s team at the Beckman Research Institute (City of Hope, CA, USA). I have performed the first multi-omics analyses of primary patient MLL-r cells by integrating data from the transcriptome, glycome, and proteome of these cells. These results revealed that MLL-r cells exhibit distinct glycosylation features that differentiate them from healthy pre-B cells, which I was able to correlate with alterations at the transcript level of relevant glycosyltransferases. In depth proteome analyses revealed an overall good correlation between proteomics and transcriptomics findings, but also uncovered numerous examples where significant changes were just found in one but not the other approach. Nevertheless, this integrated approach used for the systematic evaluation of MLL-r allowed to obtain significant data for putative novel diagnostic/therapeutic protein markers and revealed important features of the disease that remained elusive until now. I was also able to apply the developed integrated multi-omics workflow to investigate the protective role of the surrounding microenvironment and its impact in environmentmediated drug resistance (EMDR) of pre-B ALL cells, which remains a major obstacle for the efficacy of chemotherapeutics in patients. To date the relevance of glycoconjugates for the development of EMDR has been largely unexplored. I explored a long-term co-culture system using human pre-B ALL cells and mitotically inactivated supporting murine stromal cells (OP9 cells), where pre-B ALL cells were put under a selective pressure to survive in the presence of vincristine, a widely used chemotherapeutic drug. I have performed a multi-omics analyses to understand the effect vincristine-resistance has on the cells' glycocalyx. These results demonstrated both glycome-wide and glycoprotein site-specific alterations, which could potentially be employed to identify emerging drug-resistance at an earlier stage or possibly serve as treatment targets in pre-B ALL. Throughout these studies, I have observed a significant modulation of the sialylation profile on pre-B ALL cells in patients and during EMDR development. Unsurprisingly, changes in sialylation have frequently been linked with development and progression of many cancer types but remain largely unexplored in the context of pre-B ALL. I investigated the impact of the major sialyltransferase, ST6Gal1, on the glycome of pre-B ALL cells. ST6Gal1 is the transferase known to be largely responsible for attaching sialic acids in an a2-6 linkage onto N-glycans. Surprisingly, these results demonstrated that a ST6GAL1 knockout did not ablate the production of a2-6 sialylated N-glycans, unless these N-glycans carried a core fucose residue. Demonstrating for the first time how core-fucosylation regulates a2-6 sialylation also allowed me to unravel the existence of ST6Gal1 independent, alternative a2-6 sialylation pathways that are specific for non-fucosylated N-glycans. I demonstrated that ST6GalNAc3-6 are capable to produce a2-6 sialylated N-glycans in the absence of core-fucose and that ST6Gal1 is required to introduce a2-6 sialylation on corefucosylated N-glycans. These results challenge long standing dogmas in glycobiology while delivering a novel understanding of hitherto unknown mechanism that regulate protein glycosylation, which will have a significant impact on our understanding of glycosylation changes in health and disease.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)Institute for GlycomicsGriffith HealthFull Tex
Understanding storage associated changes in platelet components using glycomics: A pilot study
No full textPlatelets are crucial disk-shaped cells within the blood stream that clump together to 'plug' damaged blood vessels to prevent bleeding (haemostasis). Platelet components obtained from blood platelet donations are in high demand. The chronic shortage of platelet products is due to bacterial growth and their deterioration during storage. The recommended storage conditions see platelets being stored at [22 Degrees Celsius] for a maximum of 7 days in Australia. During this time, however, platelets deteriorate gradually, called the PSL resulting a series of biochemical changes that also lead to a heterogenous product with different patient reactions following platelet transfusion. Currently, there are no feasible laboratory markers available to assess the extent of deterioration to ensure the quality of every platelet product for transfusion, despite several metabolomic, proteomic and lipidomic studies having investigated the biochemical processes during platelet storage.
Protein glycosylation is a major component regulating platelet function, such as binding to von Willebrand factor at sites of injury and signalling for platelet clearance. However, our current knowledge if and how protein glycosylation is affected during standard storage conditions is sparse. In close collaboration with the Australian Red Cross Lifeblood R&D the aim of this work was to (i) characterise the platelet N- and O-glycome, (ii) investigate its development over 7 days of storage at room temperature, and (iii) gain an insight into the changes on (glyco)protein level using state-of-the-art glycomics and proteomics technologies. [...]Thesis (Masters)Master of Medical Research (MMedRes)School of Pharmacy & Med SciGriffith HealthFull Tex
- …
