196,773 research outputs found
Modelling self-sustained rhythmic activity in lamprey hemisegmental networks
No full textRecent studies of the lamprey spinal cord have shown that hemisegmental preparations can display rhythmic activity in response to a constant input drive. This activity is believed to be generated by a network of recurrently connected excitatory interneurons. A recent study found and characterized self-sustaining rhythmic activity—locomotor bouts—after brief electrical stimulation of hemisegmental preparations. The mechanisms behind the bouts are still unclear. We have developed a computational model of the hemisegmental network. The model addresses the possible involvement of NMDA, AMPA, acetylcholine, and metabotropic glutamate receptors as well as axonal delays in locomotor bouts
Enzymatic studies of alcohol dehydrogenase by a combination of in vitro and in silico methods
No full textThe family of alcohol dehydrogenases (ADHs) catalyzes conversions of alcohols, ketons and aldehydes. The early discovery and isolation of ADH (1937) was followed by numerous investigations. It was also the first dimeric enzyme for which the threedimensional structure was determined (1974). Recent findings have revealed new physiological functions for the ADH enzymes. One type is a key enzyme in hepatic retinol metabolism, another is a main formaldehyde scavenger and a regulator of Snitrosothiols levels. ADH genes have been shown to be connected to diseases and syndromes, such as alcoholism and asthma. Hence, investigations of structure-function relationships of the ADH enzymes are of both physiological and medical interest. The aim of this thesis was to study structure-function relationships and to investigate and identify ligands for ADH, with in vitro and in silico methods.The catalytic activities of human, mouse and rat ADH2 for retinoids, were determined. The Km values for human ADH2 are the lowest among all known human dehydrogenases, which supports a key role for human ADH2 in the hepatic retinoid metabolism. ADH3 is an enzyme with a proposed role as an NO scavenger. Two new lines of ligands, bile acids and fatty acids, were investigated for their potential effects on NO homeostasis. The bronco dilatatory effect of NO suggests that ADH3 inhibition could potentially work as treatment of obstructive lung disorders. The stability of the quaternary structure of sorbitol dehydrogenase (SDH) was determined by in vitro experiments and in silico energy calculations. A hydrogen-bonding network crucial for the tetrameric stability in SDH was identified. This network is located at a region enclosing the structural zinc site in mammalian ADHs.The structural zinc site was studied in detail by a combination of molecular dynamics and quantum mechanics simulations. The simulations revealed that the interaction between the cysteine residues and the zinc atom is of an electrostatic and covalent nature. With in silico and in vitro simulations, interactions between ligands and the active site were determined, revealing site specific interactions within both ADH2 and ADH3. Furthermore, studies of subunit interactions and the structural zinc site revealed properties of the quaternary stability.List of scientific papersI. Hellgren M, Strömberg P, Gallego O, Martras S, Farrés J, Persson B, Parés X, Höög JO (2007). Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism. Cell Mol Life Sci. 64(4): 498-505 https://pubmed.ncbi.nlm.nih.gov/17279314II. Hellgren M, Kaiser C, de Haij S, Norberg A, Höög JO (2007). A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power. Cell Mol Life Sci. 64(23): 3129-38 https://pubmed.ncbi.nlm.nih.gov/17952367III. Brandt EG, Hellgren M, Brinck T, Bergman T, Edholm O (2009). Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site. Phys Chem Chem Phys. 11(6): 975-83. Epub 2008 Dec 12 https://pubmed.ncbi.nlm.nih.gov/19177216IV. Staab CA, Hellgren M, Grafström RC, Höög JO (2009). Medium-chain fatty acids and glutathione derivatives as inhibitors of S-nitrosoglutathione reduction mediated by alcohol dehydrogenase 3. Chem Biol Interact. 180(1): 113-8. Epub 2009 Jan 29 https://pubmed.ncbi.nlm.nih.gov/19428350V. Hellgren M, Carlsson J, Östberg L, Staab C.A, Persson B, Höög JO (2009). Virtual screening for ligands to human alcohol dehydrogenase 3. [Manuscript]</p
Visual function in very low birth weight adolescents : fifteen-year follow-up of children in southeast Sweden
No full textBackground: Very low birth weight (VLBW Aims: To describe visual functions in adolescents with VLBW in comparison with a matched control group and to investigate associations with white matter damage of immaturity (WMDI), optic disc measurements and cognitive functions in the VLBW group.Subjects (Papers I-III): A total of 86 VLBW children survived the neonatal period during a 15 months period in the southeast region of Sweden. Fifty-nine of those, and 55 term control infants, participated in the 15-year follow-up study. (Paper IV): A subgroup including 18 VLBW subjects and 29 control subjects participated.Methods: Structural assessments included brain MRI, digital analysis of fundus photographs and cycloplegic refraction. Functional evaluations comprised best corrected visual acuity, stereo acuity, visual fields, ocular alignment, fixation behavior, cognitive visual problems and intellectual level.Results: Twenty-eight percent of the VLBW subjects had WMDI. The mean neural retinal rim area was smaller - in normal sized optic discs - in the VLBW than in the control group (p=0.018). The VLBW adolescents had more tortuous retinal arterioles than the controls (pConclusion: This study confirms previous observations that adolescents with VLBW are at a disadvantage regarding visual and cognitive outcome compared with adolescents with normal birth weight. Adolescents with WMDI had more pronounced visual and cognitive dysfunction.List of scientific papersI. Hellgren K, Hellström A, Jacobson L, Flodmark O, Wadsby M, Martin L (2007). "Visual and cerebral sequelae of very low birth weight in adolescents." Arch Dis Child Fetal Neonatal Ed 92(4): F259-64. https://pubmed.ncbi.nlm.nih.gov/17314116 II. Hellgren K, Hellström A, Martin L (2008). "Visual fields and optic disc morphology in very low birthweight adolescents examined with magnetic resonance imaging of the brain." Acta Ophthalmol Sep 20: Epub ahead of print. https://pubmed.ncbi.nlm.nih.gov/18811637 III. Hellgren K, Aring E, Jacobson L, Ygge J, Martin L (2008). "Visuo-spatial skills, ocular alignment and MRI findings in very low birth weight adolescents." Journal of American Association for Pediatric Ophthalmology and Strabismus. [Accepted] https://doi.org/10.1016/j.jaapos.2008.11.008 IV. Hellgren K, Han Y, Ygge J (2009). "Fixation behaviour in very low birth weight and control adolescents." [Manuscript]</p
Immune responses to mRNA vaccines : characteristics & the impact of host immune status
No full textmRNA vaccines played a critical role in combating the SARS-CoV-2 pandemic and are progressing toward wider clinical use. However, much of how mRNA vaccines act upon the immune system to induce protection remains incompletely understood. This thesis explores how mRNA vaccines interact with the cells of the immune system, focusing on B cell immunity, early inflammation, and host-specific factors.In study I, we compared a preclinical nucleoside-unmodified mRNA vaccine candidate against an antigen-matched inactivated virus vaccine. We found that two doses of unmodified mRNA vaccine induced higher peak neutralizing antibody titers and bone marrow plasma cell counts, while showing similar memory B cell somatic hypermutation and diversity. Antibody titers were cross- neutralizing and stabilized at a higher plateau at 1 year after mRNA compared to inactivated virus vaccination.In study II, we investigated how prior SARS-CoV-2 influence the early innate immune responses to nucleoside-modified mRNA vaccination in humans. We showed that mRNA vaccination induces a transient inflammatory response including moderate systemic release of proinflammatory cytokines, upregulation of type I interferon associated genes, and proportional expansion of circulating monocyte populations. In individuals with known prior SARS-CoV-2 infection, the magnitude of the innate response to the prime vaccination was increased compared to SARS-CoV-2 naïve controls. Correlation analysis associated innate immune activation to levels of pre-existing adaptive immunity.In study III, we investigated the B cell response to SARS-CoV-2 mRNA vaccination in hematopoietic stem cell transplant recipients. While those vaccinated within 12 months post-transplant had reduced antibody and memory B cell levels, the responses that did occur were functional in terms of neutralization and accumulation of somatic hypermutation in the B cell receptor. Lower responses were associated with elevated fractions of immature transitional B cells.In summary, this thesis provides insights into both the early and long-term immune responses elicited by mRNA vaccines and underscores the influence of individual host factors, such as prior antigen experience and immune repertoire composition, on vaccine responsiveness.List of scientific papersI. Hellgren F*, Cagigi A*, Arcoverde Cerveira R*, Ols S, Kern T, Lin A, Eriksson B, Dodds MG, Jasny E, Schwendt K, Freuling C, Müller T, Corcoran M, Karlsson Hedestam GB, Petsch B, Loré K. Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses. Nature Communications. 2023 Jun 22;14(1):3713. https://doi.org/10.1038/s41467-023-39421-5II. Hellgren F*, Rosdahl A*, Arcoverde Cerveira R, Lenart K, Ols S, Gwon YD, Kurt S, Delis AM, Joas G, Evander M, Normark J, Ahlm C, Forsell MN, Cajander S, Loré K. Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans. JCI Insight. 2024 May 8;9(9):e175401. https://doi.org/10.1172/jci.insight.175401III. Hellgren F, Arcoverde Cerveira R, Lindgren G, Chen P, Lenart K, Ols S, Cagigi A, Rocavert Barranco M, Shaloom Vitus E, Corcoran M, Gwon Y-D, Forsell MNE, Evander M, COVAXID Study group, Bergam P, Buggert M, Ljunggren H-G, Aleman S, Karlsson Hedestam GB, Björklund A, Nordlander A, Ljungman P, Mielke S*, Loré K *. The impact of B cell reconstitution on mRNA vaccine responses in allogeneic stem cell transplant recipients. [Manuscript]*= Equal contribution.</p
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Correlation energy within exact-exchange adiabatic connection fluctuation-dissipation theory: Systematic development and simple approximations
No full textWe have calculated the correlation energy of the homogeneous electron gas (HEG) and the dissociation energy curves of molecules with covalent bonds from an efficient implementation of the adiabatic connection fluctuation dissipation expression including the exact-exchange (EXX) kernel. The EXX kernel is defined from first-order perturbation theory and used in the Dyson equation of time-dependent density-functional theory. Within this approximation (RPAx), the correlation energies of the HEG are significantly improved with respect to the random phase approximation (RPA) up to densities of the order of rs 10. However, beyond this value, the RPAx response function exhibits an unphysical divergence and the approximation breaks down. Total energies of molecules at equilibrium are also highly accurate, but we find a similar instability at stretched geometries. Staying within an exact first-order approximation to the response function, we use an alternative resummation of the higher-order terms. This slight redefinition of RPAx fixes the instability in total energy calculations without compromising the overall accuracy of the approach. © 2014 American Physical Society
Visual perception of forms in 5-12 years old children measured by Form Test
No full textA new test of coherent form discrimination called Form Test is proposed in order to assess ventral stream functionality. The task consists of shape discrimination among 8 different forms. The form is obtained by a number white luminance coherent dots presented on a circular black background. Stimuli are presented in 5 levels of spatial coherence by increasing noise dots. Noise dots are non aligned and non coherent luminance dots which disturb shape discrimination. A sample of 163 children (75 females and 88 males, age range: 5-12) is considered. Results show significant differences among coherence levels: the number of correct answers decreases with noise increment. Moreover, the age of children affect the scores: the performance of children in Form Test improves with age. The results confirm that Form Test can be an helpful instrument to measure the ventral stream functionality and shows its sensitivity to the age differences
Cerebral visual impairment captured with a structured history inventory in extremely preterm born children aged 6.5 years
No full textPurpose: To investigate whether a questionnaire can identify cerebral visual impairment (CVI) in a group of 6.5-year-old children born extremely preterm (EPT) as accurately as direct assessments. Methods: This prospective population-based study included 120 children born before 27 weeks' gestational age (66 males; mean, 25.4 ± 1.0 weeks) and 97 full-term controls (56 males; mean, 39.9 ± 1.1 weeks) at the age of 6.5 years, as part of the Extremely Preterm Infants in Sweden Study (EXPRESS). A questionnaire for detection of CVI was evaluated and compared with visual, perceptual, and cognitive assessments. Results: Parents of children born EPT reported more CVI features than the parents of control children, with median sum scores of 25 (95% CI, 18.1-31.9) and 11 (95% CI, 8.8-13.2), respectively (P < 0.001), and a median difference of 14 (95% CI, 6.6-21.4). Low rates of reported CVI features were significantly associated with better results from direct assessments within the EPT group and with less pronounced differences compared to controls. Conclusions: The questionnaire discriminated well between children born EPT and controls, and the scores were congruent with other evidence of visual, perceptual, and cognitive deficits. The easily used questionnaire compared favorably with direct assessment in identifying CVI in children born EPT and also provides valuable information to clinicians, and parents about the daily life problems associated with CVI
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
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