| 1. |
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| 2. |
- Delios, A., et al.
(author)
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Examining the generalizability of research findings from archival data
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Journal article (peer-reviewed)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 3. |
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| 4. |
- Jones, Gregory T., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
-
In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
-
Journal article (peer-reviewed)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 5. |
- Agha, R. A., et al.
(author)
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The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines
- 2018
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In: International Journal of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1743-9191. ; 60, s. 132-136
-
Journal article (peer-reviewed)abstract
- Introduction: The SCARE Guidelines were published in 2016 to provide a structure for reporting surgical case reports. Since their publication, SCARE guidelines have been widely endorsed by authors, journal editors, and reviewers, and have helped to improve reporting transparency of case reports across a range of surgical specialties. In order to encourage further progress in reporting quality, the SCARE guidelines must themselves be kept up to date. We completed a Delphi consensus exercise to update the SCARE guidelines. Methods: A Delphi consensus exercise was undertaken. All members of the previous Delphi group were invited to participate, in addition to researchers who have previously studied case reports, and editors from the International Journal of Surgery Case Reports. The expert group was sent an online questionnaire where they were asked to rate their agreement with proposed changes to each of the 24 items. Results: 56 people agreed to participate and 45 (80%) invitees completed the survey which put forward modifications to the original guideline. The collated responses resulted in modifications. There was high agreement amongst the expert group. Conclusion: A modified and improved SCARE checklist is presented, after a Delphi consensus exercise was completed. The SCARE 2018 Statement: Updating Consensus Surgical CAse REport (SCARE) Guidelines. © 2018
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| 6. |
- Hanly, J. G., et al.
(author)
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Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus
- 2011
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1726-1732
-
Journal article (peer-reviewed)abstract
- Objective Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-beta(2) glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrolment was 5.4 +/- 4.2 months, follow-up was 3.6 +/- 2.6 years. Patients were 89.1% female with mean (+/- SD) age 35.2 +/- 13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-beta(2) glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.
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| 7. |
- Hanly, JG, et al.
(author)
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SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus
- 2011
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:6, s. 961-967
-
Journal article (peer-reviewed)abstract
- To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE).MethodsAn international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects.Results274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3±2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and −0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results.ConclusionChanges in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.
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| 8. |
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| 9. |
- Johansson, Magnus, et al.
(author)
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A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3
- 2001
-
In: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 82:Pt 4, s. 735-745
-
Journal article (peer-reviewed)abstract
- The dengue virus RNA-dependent RNA polymerase, NS5, and the protease/helicase, NS3, are multidomain proteins that have been shown to interact both in vivo and in vitro. A hyperphosphorylated form of NS5 that does not interact with NS3 has been detected in the nuclei of virus-infected cells, presumably as the result of the action of a functional nuclear localization sequence within the interdomain region of NS5 (residues 369-405). In this study, it is shown by using the yeast two-hybrid system that the C-terminal region of NS3 (residues 303-618) interacts with the N-terminal region of NS5 (residues 320-368). Further, it is shown that this same region of NS5 is also recognized by the cellular nuclear import receptor importin-beta. The interaction between NS5 and importin-beta and competition by NS3 with the latter for the same binding site on NS5 were confirmed by pull-down assays. The direct interaction of importin-beta with NS5 has implications for the mechanism by which this normally cytoplasmic protein may be targetted to the nucleus.
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| 10. |
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| 11. |
- Vasudevan, S G, et al.
(author)
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Characterisation of inter- and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets
- 2001
-
In: Il Farmaco. - : Elsevier BV. - 0014-827X .- 1879-0569. ; 56:1-2, s. 33-36
-
Journal article (peer-reviewed)abstract
- Our research is directed towards enhancing the understanding of the molecular biology of dengue virus replication with the ultimate goal being to develop novel antiviral strategies based on preventing critical inter- or intra-molecular interactions required for the normal virus life cycle. The viral RNA-dependent RNA polymerase (NS5) and the viral helicase (NS3) interaction offers a possible target for inhibitors to bind and prevent replication. In this study the yeast-two hybrid system was used to show that a small region of NS5 interacts with NS3, and also with the cellular nuclear transport receptor importin-beta. Furthermore, intramolecular interaction between the two putative domains of NS5 can also be detected by the yeast two-hybrid assay. We have also modified the colony lift assay for the beta-galactosidase reporter activity in intact yeast cells which reflects the strength of interaction between two proteins to a microtiter plate format. This assay offers a unique opportunity to screen for small molecule compounds that block physiologically important interactions.
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| 12. |
- Aulenbach, Donald B., et al.
(author)
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Removal of Heavy Metals in Publicly Owned Treatment Works
- 1987
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In: Environmental Progress. ; 6:2, s. 91-98
-
Journal article (peer-reviewed)abstract
- Studies were conducted at three activated sludge treatment plants during normal operation. The heavy metals were measured in the influent to each plant, the primary sedimentation effluent where applicable, the discharge after activated sludge treatment and secondary sedimentation, and in one case after a final polishing filter. Both the soluble and the total portions were measured. Beryllium, nickel, and thallium were not found in detectable levels in any of the plant influents. Mercury was found in only trace amounts. The removals of the other metals varied considerably. No consistent conclusions can be made from the data; each metal, soluble or total fraction, and unit treatment operation must be interpreted individually. The only metal in the plant effluents consistently above the recommended limit was arsenic, and this barely above the limit, and the lead content from Fitchburg, despite 83% removal.
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| 13. |
- Borroto-Escuela, DO, et al.
(author)
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The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
- 2021
-
In: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12, s. 627032-
-
Journal article (peer-reviewed)abstract
- The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons and glial cells. It was proposed that they form the molecular basis for learning and short-and long-term memories. This is also true for drug memories formed during the development of substance use disorders like morphine and cocaine use disorders. In cocaine use disorder it was found that irreversible A2AR-D2R complexes with an allosteric brake on D2R recognition and signaling are formed in increased densities in the ventral enkephalin positive striatal-pallidal GABA antireward neurons. In this perspective article we discuss and propose how an increase in opioid heteroreceptor complexes, containing MOR-DOR, MOR-MOR and MOR-D2R, and their balance with each other and A2AR-D2R complexes in the striatal-pallidal enkephalin positive GABA antireward neurons, may represent markers for development of morphine use disorders. We suggest that increased formation of MOR-DOR complexes takes place in the striatal-pallidal enkephalin positive GABA antireward neurons after chronic morphine treatment in part through recruitment of MOR from the MOR-D2R complexes due to the possibility that MOR upon morphine treatment can develop a higher affinity for DOR. As a result, increased numbers of D2R monomers/homomers in these neurons become free to interact with the A2A receptors found in high densities within such neurons. Increased numbers of A2AR-D2R heteroreceptor complexes are formed and contribute to enhanced firing of these antireward neurons due to loss of inhibitory D2R protomer signaling which finally leads to the development of morphine use disorder. Development of cocaine use disorder may instead be reduced through enkephalin induced activation of the MOR-DOR complex inhibiting the activity of the enkephalin positive GABA antireward neurons. Altogether, we propose that these altered complexes could be pharmacological targets to modulate the reward and the development of substance use disorders.
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| 14. |
- Brooks, Andrew J, et al.
(author)
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The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals
- 2002
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:39, s. 36399-36407
-
Journal article (peer-reviewed)abstract
- Dengue virus NS5 protein is a multifunctional RNA-dependent RNA polymerase that is essential for virus replication. We have shown previously that the 37- amino acid interdomain spacer sequence (residues (369)X(2)KKX(14)KKKX(11)RKX(3)405) of Dengue2 NS5 contains a functional nuclear localization signal (NLS). In this study, beta-galactosidase fusion proteins carrying point mutations of the positively charged residues or truncations of the interdomain linker region (residues 369-389 or residues 386-405) were analyzed for nuclear import and importin binding activities to show that the N-terminal part of the linker region (residues 369-389, a/bNLS) is critical for nuclear localization and is recognized with high affinity by the conventional NLS-binding importin alpha/beta heterodimeric nuclear import receptor. We also show that the importin beta-binding site (residues 320-368, bNLS) adjacent to the a/bNLS, previously identified by yeast two-hybrid analysis, is functional as an NLS, recognized with high affinity by importin beta, and able to target beta-galactosidase to the nucleus. Intriguingly, the bNLS is highly conserved among Dengue and related flaviviruses, implying a general role for the region and importin beta in the infectious cycle.
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| 15. |
- Brooks, Andrew J, et al.
(author)
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The Interdomain Region of Dengue NS5 ProteinInteracts with NS3 and Host Proteins
- 2002
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In: Dengue Bulletin. - 1020-895X. ; 26, s. 155-161
-
Journal article (other academic/artistic)abstract
- Although dengue virus genome replication occurs in the cytoplasm of infected cells, it has been shown that the NS5 protein (RNA-dependent RNA polymerase) is hyperphosphorylated at a late stage in infection and localized to the cell nucleus. A 37 amino acid sequence of NS5 (residues 369-405) was shown to contain a functional nuclear localization signal (NLS) that interacted with the cellular nuclear transport factor, importin α/β heterodimer. Further studies using the yeast two-hybrid system revealed that the NS5 region (residues 320-368) immediately adjacent to the NLS contained an importin β-binding site that abuts or overlaps the binding site for the NS3 protein (protease/helicase). The importin β-binding site has also been shown to be a functional NLS (bNLS). Intriguingly, when both bNLS and NLS (residues 320-405) were present, the fused β -galactosidase protein did not accumulate in the nucleus. Here we provide a review of our studies on the NS5 interdomain region and compare it to other members of the Flavivirus genus in order to highlight the importance of this region as a possible target for developing broad-acting antiviral agent against dengue and other mechanistically-related viruses.
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| 16. |
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| 17. |
- Johnston, Jennifer J., et al.
(author)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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In: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Journal article (peer-reviewed)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 18. |
- Kajtez, Janko, et al.
(author)
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3D-Printed Soft Lithography for Complex Compartmentalized Microfluidic Neural Devices
- 2020
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In: Advanced Science. - : Wiley. - 2198-3844. ; 7:16
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Journal article (peer-reviewed)abstract
- Compartmentalized microfluidic platforms are an invaluable tool in neuroscience research. However, harnessing the full potential of this technology remains hindered by the lack of a simple fabrication approach for the creation of intricate device architectures with high-aspect ratio features. Here, a hybrid additive manufacturing approach is presented for the fabrication of open-well compartmentalized neural devices that provides larger freedom of device design, removes the need for manual postprocessing, and allows an increase in the biocompatibility of the system. Suitability of the method for multimaterial integration allows to tailor the device architecture for the long-term maintenance of healthy human stem-cell derived neurons and astrocytes, spanning at least 40 days. Leveraging fast-prototyping capabilities at both micro and macroscale, a proof-of-principle human in vitro model of the nigrostriatal pathway is created. By presenting a route for novel materials and unique architectures in microfluidic systems, the method provides new possibilities in biological research beyond neuroscience applications.
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| 19. |
- Lindgren, Gustav, et al.
(author)
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Elasticity Modulation Due to Polarization Reversal and Ionic Motion in the Ferroelectric Superionic Conductor KTiOPO4
- 2018
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In: ACS Applied Materials and Interfaces. - : American Chemical Society. - 1944-8244 .- 1944-8252. ; 10:38, s. 32298-32303
-
Journal article (peer-reviewed)abstract
- The coupling between ionic degrees of freedom and ferroelectricity has received renewed attention in recent years, given that surface electrochemical processes have been shown to be intrinsically linked to ferroelectric phase stability in ultrathin ferroelectric films. However, the coupling between bulk ionic transport and local polarization switching has received less attention, as typically the bulk ionic mobilities are low for common ferroelectrics at room temperature. Here, we use the coupled band-excitation method in conjunction with site-correlated time-of-flight secondary ion mass spectrometry, to determine the coupling between ferroelectric switching and ionic motion in single crystal KTiOPO4. The local scanning probe measurements indicate a substantial softening, as determined by resonant frequency changes, during reversal of polarization along one direction. These changes are correlated with the mass spectrometry measurements, showing a polarization-dependent accumulation of K ions at the polar surfaces, thus corroborating their role in the screening process. These studies shed light on the interplay between ionic dynamics and bulk ferroelectric switching and have implications for studies on domain wall conductivity, chemical switching, and bulk and surface-screening phenomena.
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| 20. |
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| 21. |
- Lloyd-Donald, P, et al.
(author)
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Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease
- 2020
-
In: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723. ; 26, s. 1076029620925915-
-
Journal article (peer-reviewed)abstract
- Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population. Methods: In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis. Results: We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: R 2 = 0.117 ( P = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: R 2 = 0.202 ( P < .0001) and TEG (CK) α angle and fibrinogen 0.263 ( P < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: R 2 = 0.485 ( P < .0001). There were no associations between TEG and D-dimer levels. Conclusions: In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.
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| 22. |
- Lore, K, et al.
(author)
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Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells
- 2005
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 201:12, s. 2023-2033
-
Journal article (peer-reviewed)abstract
- Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against pathogens such as human immunodeficiency virus (HIV)-1. At the same time, HIV-1 replication is strongly enhanced in DC–T cell clusters, potentially undermining this process. We found that immature CD123+ plasmacytoid DCs (PDCs) and CD11c+ myeloid DCs (MDCs) were susceptible to both a CCR5- and a CXCR4-using HIV-1 isolate in vitro and were able to efficiently transfer that infection to autologous CD4+ T cells. Soon after HIV-1 exposure, both PDCs and MDCs were able to transfer the virus to T cells in the absence of a productive infection. However, once a productive infection was established in the DCs, newly synthesized virus was predominantly spread to T cells. HIV-1 exposure of the MDCs and PDCs did not inhibit their ability to present cytomegalovirus (CMV) antigens and activate CMV-specific memory T cells. As a result, both PDCs and MDCs preferentially transmitted HIV-1 to the responding CMV antigen–specific CD4+ T cells rather than to nonresponding T cells. This suggests that the induction of antigen-specific T cell responses by DCs, a process crucial to immune defense, can lead to preferential HIV-1 infection and the deletion of responding CD4+ T cells.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Ostergaard, Pia, et al.
(author)
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Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy.
- 2012
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:2
-
Journal article (peer-reviewed)abstract
- We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.
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| 27. |
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| 28. |
- Syu, Fu Siang, et al.
(author)
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Usability and Usefulness of Circularity Indicators for Manufacturing Performance Management
- 2022
-
In: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 105, s. 835-840
-
Conference paper (peer-reviewed)abstract
- Advances in industrial digitalization present many opportunities for process and product data exploitation in manufacturing, unlocking new systemic measures of performance beyond a single machine, process, facility area and even beyond the factory gates. However, existing data models and manufacturing systems' performance measures are still focused on productivity, quality and delivery time, which could potentially lead to an accelerated linear economy. To shift to more circular industrial systems, we need to identify and assess circularity opportunities in ways that align the goals of sustainable and industrial development. In this study, micro-level circular indicators were reviewed, selected, analysed and tested in a manufacturing company to evaluate their usability and usefulness to guide process improvements. The aim is to enable circular and eco-efficient solutions towards sustainable production systems. Usability and usefulness of the indicators are essential to their integration into established environmental and operations management systems. The main contribution of this study is in the identification of key features making circularity indicators usable and useful from a manufacturer's perspective. The conclusion also suggests directions for further research on tools and methods to support circular manufacturing.
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| 29. |
- Tormo-Badia, Neivis, et al.
(author)
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Antibiotic treatment of pregnant non-obese diabetic (NOD) mice leads to altered gut microbiota and intestinal immunological changes in the offspring.
- 2014
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In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 80:4, s. 250-260
-
Journal article (peer-reviewed)abstract
- The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors like diet, disease and antibiotic treatment. However, already in utero these environmental factors can affect the immunological development of the fetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared to offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared to offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development. This article is protected by copyright. All rights reserved.
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| 30. |
- Vasudevan, Subhash G, et al.
(author)
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Characterisation of inter- and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets.
- 2001
-
In: Il Farmaco. - 0014-827X .- 1879-0569. ; 56:1-2, s. 33-36
-
Journal article (peer-reviewed)abstract
- Our research is directed towards enhancing the understanding of the molecular biology of dengue virus replication with the ultimate goal being to develop novel antiviral strategies based on preventing critical inter- or intra-molecular interactions required for the normal virus life cycle. The viral RNA-dependent RNA polymerase (NS5) and the viral helicase (NS3) interaction offers a possible target for inhibitors to bind and prevent replication. In this study the yeast-two hybrid system was used to show that a small region of NS5 interacts with NS3, and also with the cellular nuclear transport receptor importin-beta. Furthermore, intramolecular interaction between the two putative domains of NS5 can also be detected by the yeast two-hybrid assay. We have also modified the colony lift assay for the beta-galactosidase reporter activity in intact yeast cells which reflects the strength of interaction between two proteins to a microtiter plate format. This assay offers a unique opportunity to screen for small molecule compounds that block physiologically important interactions.
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