1,721,009 research outputs found
Solution NMR analyses of the C-type carbohydrate recognition domain of DC-SIGNR protein reveal different binding modes for HIV-derived oligosaccharides and smaller glycan fragments
No full textBackground: DC-SIGNR, a C-type lectin which promotes infection of pathogens such as HIV, is a promising drug target.
Results: Carbohydrate recognition domain of DC-SIGNR is highly dynamic, displaying unique binding modes for individual glycans.
Conclusion: More complex, disease-associated glycans have different binding modes than smaller glycans previously studied.
Significance: Understanding ligand-binding properties and solution dynamics of DC-SIGNR will facilitate therapeutic desig
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
Investigating peripheral metabolites and lipids as potential biomarkers for Major Depressive Disorder
Full text linkMajor Depressive Disorder (MDD) poses significant clinical challenges due to its complicated and elusive pathophysiology. This thesis seeks to fill research gaps in understanding MDD by investigating peripheral metabolites and lipids as potential biomarkers which could be used to improve diagnosis and prognosis of this debilitating mental health condition. Small molecules, such as amino acids, that are involved in energy homeostasis are of particular interest to investigate alongside lipids because mood disorders are strongly associated with metabolic dysfunction. A systematic review and meta-analysis was first conducted on articles reporting metabolomic analyses on amino acids and demonstrated significantly elevated citrate, alanine, and glutamate levels in peripheral biofluids from depressed people compared to healthy individuals. The investigation analyzed metabolomic and lipidomic data from UK twin populations, focusing on individuals assessed using the Hospital Anxiety and Depression Scale (HADS). Participants meeting inclusion criteria had at least one HADS score and <15% missing data. With 1,532 entries, the primary emphasis was on a two-year database, revealing insights into twin health, including 43 Normal, 35 Borderline Abnormal, and 35 Abnormal samples. This comprehensive study illuminated connections between lifestyle factors, inflammatory markers, lipidomics, and MDD severity. Positive associations between smoking and alcohol consumption underscored gender-specific implications and negative correlations between exercise and HADS suggested a protective relationship against depression, aligning with established benefits for mental well-being. Pyruvate and tyrosine were found to be positively associated with depression, while alanine and acetate were negatively associated with depression. However, none of these associations were statistically significant. Multiple regression study found positive relationships between IDLFC, SLDLL, LDLC, and HADS levels, while others exhibited significant negative associations. SLDLCE and SLDLFC were found to have the highest impact on HADS scores, highlighting the complex nature of lipid metabolism in depression. Furthermore, the inverse connection between cholesterol and cholesterol esters in small and medium LDL particles and depression severity shows that cholesterol may be a more important biomarker for major depressive disorder (MDD), regardless of lipoprotein size or density. The OPLS-DA model effectively distinguished normal and abnormal mental health categories, highlighting the discriminative potential of metabolite biomarkers. Conspicuously, "AcAce" led with a VIP score of 2.24, followed by "BOHBut" (1.89) and "Ala" (1.75), emphasizing their impact. The lipid analysis illuminated complex shifts in cholesterol metabolism and lipid species, accentuating their crucial role in the pathophysiology of depression. "FreeC" stood out with a VIP score of 1.04, indicating its significant predictive influence, while "SM" closely followed with a score of 1.03. Additionally, "IDLFC" and "LLDLL" demonstrated remarkable importance, with VIP scores of 1.02 and 1.01, respectively, capturing essential data patterns. Comorbidity was found to influence lipid profiles, emphasizing the need to consider psychiatric conditions in research and clinical practice. Collectively, these findings contribute valuable insights into the multifaceted nature of MDD, proposing potential new biomarkers that may refine diagnostic accuracy and deepen our comprehension of this complex disorder
Metabolomics for biomarker discovery in neurological disorders
Full text linkBlood-borne metabolites can serve as readily accessible biomarkers reflecting biochemical alterations in neurological diseases, facilitating diagnostic, therapeutic and prognostic determination. In neurological disorders with overlapping symptoms, but with different aetiologies, timely diagnosis and appropriate treatment are crucial for optimal prognosis. This thesis employed nuclear magnetic resonance (NMR)-based metabolomics for biomarker discovery to improve diagnostics for antibody-mediated neurological disease.
1H NMR is used for metabolite measurement due to its high reproducibility, instrument stability, minimal sample preparation requirements and ability to detect a wide range of biologically significant metabolites. Here, the effectiveness of NMR-based metabolomics to distinguish between disease classes was explored using orthogonal partial least squares-discriminant analysis (OPLS-DA), with 10-fold cross-validation with repetition and permutation testing. Plasma samples from a cohort comprising patients with autoimmune encephalitis (AE) and those with drug-resistant epilepsy (DRE) were analysed. NMR-based metabolomics effectively distinguished AE from DRE, achieving a high predictive accuracy of 87.0 ± 3.1%. This method also enabled the stratification of AE subtypes (NMDAR-Ab, LGI1-Ab, CASPR2-Ab AE), with subtype-specific metabolite signatures observed. Therefore, NMR-based blood tests are able to complement current autoantibody assays and could provide a faster, cost-effective, and highly accurate adjunct for AE diagnosis. The same methodology was then applied to serum samples from psychosis patients with and without the neuronal surface antibodies in common with those found in AE. A distinct metabolic signature, including decreased lipoprotein fatty acids and increased branched-chain amino acids and glucose, was identified in psychosis patients with voltage-gated potassium channel (VGKC) or glycine receptor (GlyR) antibodies. These patients have more severe psychotic presentations, suggesting a unique inflammatory subtype.
To facilitate clinical translation, this thesis work then addressed preanalytical variability in blood samples by investigating the impact of pre-processing delays, post-processing delays, and different blood collection tubes on metabolite variability. A significant source of variability in blood was identified as the conversion of glucose to lactate owing to delays in blood pre-processing. However, it was discovered that the fluoride oxalate collection tubes effectively stabilise glucose and lactate levels for 24 hours at either 4 °C or room temperature, providing a viable alternative when rapid processing is not feasible.
Preanalytical variability can also arise in brain NMR metabolomics owing to suboptimal extractions. Investigations using rodent brain samples revealed that metabolites such as aspartate, acetate, N-acetyl aspartate, and glutamate exhibited instability as a consequence of inadequate protein precipitation with 50% acetonitrile or methanol. Conversely, a methanol/water/chloroform extraction method provides the necessary reproducibility and extraction efficiency while effectively preserving metabolite stability by sufficient protein precipitation. This method can, therefore, be recommended for untargeted brain NMR metabolomics, as it enables the reliable detection of metabolic alterations at the site of pathology, complementing histological analysis and enhancing diagnostic precision.
In conclusion, this thesis has demonstrated the potential of NMR-based metabolomics to be a powerful tool for distinguishing antibody-mediated neurological conditions, with the potential to enhance diagnostic precision, inform therapeutic strategies, and improve the understanding of disease mechanisms. By addressing preanalytical variability in both blood and brain metabolomics, this work has provided a blueprint to enhance the reliability and reproducibility of metabolomic analyses, leading to more accurate and consistent diagnostic and research outcomes
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
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
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