| 2121. |
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| 2122. |
- Ryberg, C, et al.
(författare)
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White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study.
- 2008
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Ingår i: AJNR. American journal of neuroradiology. - 1936-959X. ; 29:8, s. 1498-504
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects. MATERIALS AND METHODS: In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions. RESULTS: Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy. CONCLUSION: Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.
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| 2123. |
- Sabelström, H., et al.
(författare)
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Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8, s. 11-2079
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Tidskriftsartikel (refereegranskat)abstract
- Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 in vivo and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM. Sabelström et al. show that the loss of neurogenesis is reversible during neural stem cell-derived glioma formation. Pharmacological inhibition of ERK1/2 globally regulates miRNAs and induces neuronal differentiation, a process that is dependent on the modulation of an miR-124-SOX9 axis in glioblastoma (GBM) cells. The overexpression of miR-124 induces neuronal differentiation that abrogates GBM aggressiveness.
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| 2124. |
- Saberi, S., et al.
(författare)
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BabA Protein Expression and Lewis b Binding is Gene Locus-Dependent
- 2015
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Ingår i: Helicobacter. - : John Wiley & Sons. - 1083-4389 .- 1523-5378. ; 20:Suppl. 1, s. 111-111
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Helicobacter pylori (Hp) adhesion, BabA, is localized on the bacterial cell surface, binds to the fucosylated Lewis b histo-blood group antigen on gastric epithelial cells and is responsible for bacterial colonization in the gastric milieu. The diverse roles of this bacterial adhesion in Hp-induced pathogenesis remain understudied.Methods: We have isolated single colonies of Hp from 156 (NUD=97, DU=34, GC=25) patients. babA and babB genes were evaluated by gene/locus-specific PCR. BabA protein expression and Lewis b (Leb) binding capacity were determined by immunoblotting and ELISA, respectively.Results: Leb binding assay identified 36% of the strains as high binders and the remaining 64% with low binding capacity. All (100%) of the strains in the former group expressed BabA protein at high levels (BabA-H). Of the latter group, 40% were BabA low producers (BabA-L) and the remaining 60% produced no detectable BabA protein (BabA-Neg). The majority (73/88, 83%) of the strains expressing BabA protein were babA gene-positive at locus A versus. those at locus B (15/88, 17%, P = 0.034). The same holds true for Lewis b binding. In other words, the former group constitutes larger numbers (44/50, 88%) of Leb high-binders relative to the latter group (6/50, 12%, P = 0.035). Furthermore, amongst the former group, co-presence of babA and babB genes in locus A reduced the probability of Leb binding (P = 0.0001).Conclusion: Presence of babA gene in locus A is associated with higher BabA protein expression and Lewis b binding. Therefore, gene/locus-specific PCR seems better suited for the assessment of functional BabA protein.
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| 2125. |
- Sagafors, Dagrun, et al.
(författare)
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Single-Fiber Recordings Of Nociceptive Fibers in Patients With HSAN Type V With Congenital Insensitivity To Pain
- 2016
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Ingår i: The Clinical Journal of Pain. - 0749-8047 .- 1536-5409. ; 32:7, s. 636-642
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Nerve growth factor (NGF) is a protein important for growth and survival, but also for modulation of sensitivity of nociceptors and sympathetic neurons. The purpose of the present study was to investigate the effects of reduced NGF signaling in patients with hereditary sensory and autonomic neuropathies type V, congenital insensitivity to pain, caused by a mutation of the NGF beta gene, including a characterization of single nociceptive fibers using microneurography (MNG).Materials and Methods: One homozygote and 2 heterozygote patients with this mutation were examined with electromyography/neurography, thermal testing, quantitative sudomotor axon reflex test, and electrically induced axon reflex erythema in addition to MNG.Results: Low quantitative sudomotor axon reflex test measurements of 0.02 (left foot) and 0.03 (right foot) mL/cm(2) and elevated thermal thresholds for warmth and cold detection testing showed clear impairment of small nerve fibers, both sudomotor efferent and somatic afferent fibers, in the patient homozygote for the mutation. MNG from one of the heterozygote patients revealed changes in the small nociceptive fibers in skin, including abnormally low conduction velocity, spontaneous activity in A-delta fibers and C-nociceptors and abnormal or lacking response to heat.Discussion: The findings of grossly intact pain thresholds compared with anamnestic insensitivity of pain in deep somatic tissue such as bone suggest a gradient of impairment dependent on different NGF availability in various tissues. Even though these patients in some aspects report insensitivity to pain, they also report chronic spontaneous pain as their main symptom, strikingly highlighting differential mechanisms of insensitivity to evoked pain versus spontaneous pain.
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| 2126. |
- Sahlén, Martin, et al.
(författare)
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Experimental Verification of the Chemical Sensitivity of Two-Site Double Core-Hole States Formed by an X-Ray Free-Electron Laser
- 2012
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 108:15, s. 153003-
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Tidskriftsartikel (refereegranskat)abstract
- We have performed x-ray two-photon photoelectron spectroscopy using the Linac Coherent Light Source x-ray free-electron laser in order to study double core-hole (DCH) states of CO2, N2O, and N-2. The experiment verifies the theory behind the chemical sensitivity of two-site DCH states by comparing a set of small molecules with respect to the energy shift of the two-site DCH state and by extracting the relevant parameters from this shift.
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| 2127. |
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| 2128. |
- Sanchez, J. C., et al.
(författare)
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High-resolution crystal structures of amyxobacterial phytochrome at cryo and roomtemperatures
- 2019
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Ingår i: Structural Dynamics-Us. - : AIP Publishing. - 2329-7778. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes (PHYs) are photoreceptor proteins first discovered in plants, where they control a variety of photomorphogenesis events. PHYs as photochromic proteins can reversibly switch between two distinct states: a red light (Pr) and a far-red light (Pfr) absorbing form. The discovery of Bacteriophytochromes (BphPs) in nonphotosynthetic bacteria has opened new frontiers in our understanding of the mechanisms by which these natural photoswitches can control single cell development, although the role of BphPs in vivo remains largely unknown. BphPs are dimeric proteins that consist of a photosensory core module (PCM) and an enzymatic domain, often a histidine kinase. The PCM is composed of three domains (PAS, GAF, and PHY). It holds a covalently bound open-chain tetrapyrrole (biliverdin, BV) chromophore. Upon absorption of light, the double bond between BV rings C and D isomerizes and reversibly switches the protein between Pr and Pfr states. We report crystal structures of the wild-type and mutant (His275Thr) forms of the canonical BphP from the nonphotosynthetic myxobacterium Stigmatella aurantiaca (SaBphP2) in the Pr state. Structures were determined at 1.65A degrees and 2.2A degrees (respectively), the highest resolution of any PCM construct to date. We also report the room temperature wild-type structure of the same protein determined at 2.1A degrees at the SPring-8 Angstrom Compact free electron LAser (SACLA), Japan. Our results not only highlight and confirm important amino acids near the chromophore that play a role in Pr-Pfr photoconversion but also describe the signal transduction into the PHY domain which moves across tens of angstroms after the light stimulus. (C) 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 2129. |
- Sandvik, R. M., et al.
(författare)
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Contemporary N-2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis
- 2022
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Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6MBW commonly viewed as the reference method. The use of N2MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N(2 )signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2MBW,corrected-such as tidal volume reduction during N-2 washout with pure O-2. Method This was a longitudinal multicenter cohort study. SF6MBW and N2MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N-2,N-original and N-2,N-corrected for comparison with SF6MBW. Results Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original, and 1.0% different from FRCSF6. Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original, and 7.3% higher than LCISF6. Mean (SD) tidal volume decreased significantly during N2MBWcorrected, compared to SF6MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6. The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6) and (0.23/LCISF6), respectively, for N-2,N-original and N-2,N-corrected, but the relative differences were stable across disease severity for N-2,N-corrected, but not for N-2,N-original. Conclusion Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2MBW did not affect differences. The corrected N2MBW can now be used with confidence in young children with CF, although not interchangeably with SF6.
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| 2130. |
- Sandvik, R. M., et al.
(författare)
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Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis
- 2023
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Ingår i: European Respiratory Journal Open Research (ERJ Open Research). - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. Methods This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. Results 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.222.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78-0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15-1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Conclusions Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.
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