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  • Kotarsky, Heike, et al. (författare)
  • BCS1L is expressed in critical regions for neural development during ontogenesis in mice.
  • 2007
  • Ingår i: Gene Expression Patterns. - : Elsevier. - 1567-133X. ; 7, s. 266-273
  • Tidskriftsartikel (refereegranskat)abstract
    • BCS1L is a chaperone necessary for the incorporation of Rieske Fes and Qcr10p into complex III (CIII) of the respiratory chain. Mutations in the BCS1L gene cause early fetal growth restriction and a lethal neonatal disease in humans, however, the pathogenesis remains unclear. Here, we analysed the expression of BCS1L during mouse embryonic development and compared its expression with that of the mitochondrial markers Porin, GRIM 19, Core 1, and Rieske Fes. BCS1L was strongly expressed in embryonic tissues already at embryonic days 7 (E7) and 9 whereas the expression of Porin and Rieske Fes was not as evident at this time point. At E 11, BCS1L, Porin, and Rieske Fes had overlapping expression patterns in organs known to contain high numbers of mitochondria such as heart, liver and somites. In contrast, BCS1L was differently distributed compared to the mitochondrial proteins Porin, Rieske FeS, Core I and Grim 19 in the floor plate of the E 11, E 12 and E 13 neural tube. These results show that the expression pattern of BCS1L only partially overlaps with the expression of Porin and Rieske Fes. Thus, BCS1L alone or in cooperation with Rieske FES may during development have previously unknown functions beside its role in assembly of complex III. The floor plate of the neural tube is essential for dorsal ventral patterning and the guidance of the developing neurons to their targets. The predominant expression of BCS1L in this region, together with its presence in peripheral ganglia from E13 onwards, indicates a role for BCS1L in the development of neural structures. (c) 2006 Elsevier B.V. All rights reserved.
  • Kotarsky, Heike, et al. (författare)
  • Characterization of complex III deficiency and liver dysfunction in GRACILE syndrome caused by a BCS1L mutation.
  • 2010
  • Ingår i: Mitochondrion. - : Elsevier. - 1567-7249. ; Jul 1, s. 497-509
  • Tidskriftsartikel (refereegranskat)abstract
    • A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondrial membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex III, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction.
  • Kotarsky, Heike, et al. (författare)
  • Metabolite Profiles Reveal Energy Failure and Impaired Beta-Oxidation in Liver of Mice with Complex III Deficiency Due to a BCS1L Mutation.
  • 2012
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:7
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2)O(2) production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.
  • Kotilahti, Kalle, et al. (författare)
  • Hemodynamic Responses to Speech and Music in Newborn Infants
  • 2010
  • Ingår i: Human Brain Mapping. - : Wiley-Blackwell. - 1065-9471. ; 31:4, s. 595-603
  • Tidskriftsartikel (refereegranskat)abstract
    • We used near-infrared spectroscopy (NIRS) to study responses to speech and music on the auditory cortices of 13 healthy full-term newborn infants during natural sleep. The purpose of the study was to investigate the lateralization of speech and music responses at this stage of development. NIRS data was recorded from eight positions on both hemispheres simultaneously with electroencephalography, electrooculography, electrocardiography, pulse oximetry, and inclinometry. In 11 subjects, statistically significant (P < 0.02) oxygenated (HbO(2)) and total hemoglobin (HbT) responses were recorded. Both stimulus types elicited significant HbO(2) and HUT responses on both hemispheres in five subjects. Six of the 11 subjects had positive HbO(2) and HbT responses to both stimulus types, whereas one subject had negative responses. Mixed positive and negative responses were observed in four neonates. On both hemispheres, speech and music responses were significantly correlated (r = 0.64; P = 0.018 on the left hemisphere (LH) and r = 0.60; P = 0.029 on the right hemisphere (RH)). On the group level, the average response to the speech stimuli was statistically significantly greater than zero in the LH, whereas responses on the RH or to the music stimuli did not differ significantly from zero. This suggests a more coherent response to speech on the LH. However, significant differences in lateralization of the responses or mean response amplitudes of the two stimulus types were not observed on the group level. Hum Brain Mapp 31:595-603, 2010. (C) 2009 Wiley-Liss, Inc.
  • Kotilahti, K, et al. (författare)
  • Near-infrared spectroscopic imaging of stimulus-related hemodynamic responses on the neonatal auditory cortices.
  • 2005
  • Ingår i: Optical tomography and spectroscopy of tissue VI. - : SPIE. - 0277-786X .- 1996-756X. - 9780819456670 ; 5693, s. 388-395
  • Konferensbidrag (refereegranskat)abstract
    • We have used near-infrared spectroscopy (NIRS) to study hemodynamic auditory evoked responses on 7 full-term neonates. Measurements were done simultaneously above both auditory cortices to study the distribution of speech and music processing between hemispheres using a 16-channel frequency-domain instrument. The stimulation consisted of 5-second samples of music and speech with a 25-second silent interval. In response to stimulation, a significant increase in the concentration of oxygenated hemoglobin ([HbO2]) was detected in 6 out of 7 subjects. The strongest responses in [HbO2] were seen near the measurement location above the ear on both hemispheres. The mean latency of the maximum responses was 9.42±1.51 s. On the left hemisphere (LH), the maximum amplitude of the average [HbO2] response to the music stimuli was 0.76± 0.38 μ M (mean±std.) and to the speech stimuli 1.00± 0.45 μ± μM. On the right hemisphere (RH), the maximum amplitude of the average [HbO2] response was 1.29± 0.85 μM to the music stimuli and 1.23± 0.93 μM to the speech stimuli. The results indicate that auditory information is processed on both auditory cortices, but LH is more concentrated to process speech than music information. No significant differences in the locations and the latencies of the maximum responses relative to the stimulus type were found.
  • Krite Svanberg, Emilie, et al. (författare)
  • Diode laser spectroscopy for non-invasive monitoring of oxygen in the lungs of newborn infants.
  • 2016
  • Ingår i: Pediatric Research. - : International Pediatric Foundation Inc.. - 1530-0447. ; 79, s. 621-628
  • Tidskriftsartikel (refereegranskat)abstract
    • Newborn infants have pulmonary disorders with abnormal gas distribution, e. g. respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel non-invasive optical technique for rapid non-radiographic bedside detection of oxygen gas in the lungs of full-term newborn infants.
  • Kujala, A, et al. (författare)
  • Speech-sound discrimination in neonates as measured with MEG
  • 2004
  • Ingår i: NeuroReport. - : Lippincott Williams & Wilkins. - 1473-558X. ; 15:13, s. 2089-2092
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetic brain responses to speech sounds were measured in 10 healthy neonates. The stimulation consisted of a frequent vowel sound [a] with a steady pitch contour, which was occasionally replaced by the vowel [i:] with a steady pitch, or the vowel [a] with a rising pitch, manifesting a change of intonation. The magnetic mismatch-negativity response (MMNm) was obtained and successfully modelled to the speech sound quality change in all infants and to the intonation change in 6 infants. The present results indicate that auditory-cortex speech-sound discrimination may well be studied with magnetic recordings as early as in newborn infants.
  • Kushnerenko, Elena, et al. (författare)
  • Processing acoustic change and novelty in newborn infants
  • 2007
  • Ingår i: European Journal of Neuroscience. - : Wiley-Blackwell. - 1460-9568. ; 26:1, s. 265-274
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed 'novel' sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound [Kushnerenko et al., (2002) NeuroReport, 13, 1843-1848]. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the 'novel' sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a 'standard' sound presented with the probability of 0.8 and two types of infrequent 'deviant' sounds (0.1 probability, each). Deviants were (i) 'novel' sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system.
  • Larsson, Jim, et al. (författare)
  • Comparison of dermal vs internal light administration in human lungs using the TDLAS-GASMAS technique—Phantom studies
  • 2019
  • Ingår i: Journal of Biophotonics. - : John Wiley & Sons Inc.. - 1864-063X. ; 12:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxygen and water vapor content, in the lungs of a 3D-printed phantom model based on CT-images of a preterm infant, is evaluated using Tunable Diode Laser Absorption Spectroscopy (TDLAS) in Gas in Scattering Media Absorption Spectroscopy (GASMAS), that is, the TDLAS-GASMAS technique. Oxygen gas is detected through an absorption line near 764 nm and water vapor through an absorption line near 820 nm. A model with a lung containing interior structure is compared to a model with a hollow lung. Compared to the model with the hollow lung, both the mean absorption path length and the transmitted intensity are found to be lower for the model with the structured lung. A new approach, where laser light is delivered internally into the model through an optical fiber, is compared to dermal light administration, that is, illumination onto the skin, for the model with structure inside the lung. The internal light administration generally resulted in larger gas absorption, and higher signal-to-noise ratios, compared to the dermal light administration. The results from the phantom measurements show great promise for the internal illumination approach and a natural next step would be to investigate it further in clinical studies.
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