Michael Nilsson

Summary

Affiliation: Sahlgrenska University Hospital
Country: Sweden

Publications

  1. ncbi Losses of NG2 and NeuN immunoreactivity but not astrocytic markers during early reperfusion following severe focal cerebral ischemia
    Diane R Lee
    Centre for Neuroscience and Department of Medical Biochemistry, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia
    Brain Res 989:221-30. 2003
  2. ncbi Enriched environment and astrocytes in central nervous system regeneration
    Michael Nilsson
    Center for Brain Repair and Rehabilitation CBR, Department of Clinical Neuroscience and Rehabilitation, Institute for Neuroscience and Physiology, Sahlgrenska Academy, Goteborg University, Goteborg, Sweden
    J Rehabil Med 39:345-52. 2007
  3. pmc Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane
    Michelle J Porritt
    Center for Brain Repair and Rehabilitation CBR, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 7:e41090. 2012
  4. pmc Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease
    Malin von Otter
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Bla Straket 15, 413 45 Gothenburg, Sweden
    BMC Med Genet 11:36. 2010
  5. pmc Plasticity response in the contralesional hemisphere after subtle neurotrauma: gene expression profiling after partial deafferentation of the hippocampus
    Daniel Andersson
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 8:e70699. 2013
  6. doi Age-dependent regenerative responses in the striatum and cortex after hypoxia-ischemia
    Changlian Zhu
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    J Cereb Blood Flow Metab 29:342-54. 2009
  7. ncbi X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants
    Changlian Zhu
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Goteborg University, Box 432, SE 405 30 Goteborg, Sweden
    Eur J Neurosci 26:3402-10. 2007
  8. ncbi Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia
    Jenny Nyberg
    1 Centre for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Brain 137:1514-23. 2014
  9. doi Expression of plasminogen activator inhibitor-1 and protease nexin-1 in human astrocytes: Response to injury-related factors
    Karin Hultman
    Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
    J Neurosci Res 88:2441-9. 2010
  10. ncbi Decreased oxidative stress during glycolytic inhibition enables maintenance of ATP production and astrocytic survival
    Christina Nodin
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden
    Neurochem Int 61:291-301. 2012

Collaborators

Detail Information

Publications45

  1. ncbi Losses of NG2 and NeuN immunoreactivity but not astrocytic markers during early reperfusion following severe focal cerebral ischemia
    Diane R Lee
    Centre for Neuroscience and Department of Medical Biochemistry, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia
    Brain Res 989:221-30. 2003
    ..These findings provide the first evidence of marked sensitivity of NG2-immunoreactivity to severe ischemia and suggest a greater initial resistance of astrocytes compared with neurons and NG2-positive glia to ischemia-reperfusion damage...
  2. ncbi Enriched environment and astrocytes in central nervous system regeneration
    Michael Nilsson
    Center for Brain Repair and Rehabilitation CBR, Department of Clinical Neuroscience and Rehabilitation, Institute for Neuroscience and Physiology, Sahlgrenska Academy, Goteborg University, Goteborg, Sweden
    J Rehabil Med 39:345-52. 2007
    ..It also summarizes research showing that astrocytes - considered only years ago merely to nurse and support neurones - are a novel and highly interesting target for regenerative strategies in the brain and spinal cord...
  3. pmc Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane
    Michelle J Porritt
    Center for Brain Repair and Rehabilitation CBR, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 7:e41090. 2012
    ..The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage...
  4. pmc Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease
    Malin von Otter
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Bla Straket 15, 413 45 Gothenburg, Sweden
    BMC Med Genet 11:36. 2010
    ..Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease...
  5. pmc Plasticity response in the contralesional hemisphere after subtle neurotrauma: gene expression profiling after partial deafferentation of the hippocampus
    Daniel Andersson
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 8:e70699. 2013
    ..We conclude that even a very limited focal neurotrauma triggers a distinct response at the contralesional side, which at least to some extent depends on astrocyte activation. ..
  6. doi Age-dependent regenerative responses in the striatum and cortex after hypoxia-ischemia
    Changlian Zhu
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    J Cereb Blood Flow Metab 29:342-54. 2009
    ..The biggest ischemia-induced change was the 49-fold increase in P21 striatal microglia, and this was accompanied by increased inflammation, as judged by the size and numbers of CCL2- and interleukin-18-positive cells...
  7. ncbi X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants
    Changlian Zhu
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Goteborg University, Box 432, SE 405 30 Goteborg, Sweden
    Eur J Neurosci 26:3402-10. 2007
    ....
  8. ncbi Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia
    Jenny Nyberg
    1 Centre for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Brain 137:1514-23. 2014
    ....
  9. doi Expression of plasminogen activator inhibitor-1 and protease nexin-1 in human astrocytes: Response to injury-related factors
    Karin Hultman
    Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
    J Neurosci Res 88:2441-9. 2010
    ..We show here that human astrocytes express PAI-1 and PN-1 and demonstrate that this astrocytic expression is regulated in a dynamic manner by injury-related factors...
  10. ncbi Decreased oxidative stress during glycolytic inhibition enables maintenance of ATP production and astrocytic survival
    Christina Nodin
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden
    Neurochem Int 61:291-301. 2012
    ....
  11. doi Repeated transient sulforaphane stimulation in astrocytes leads to prolonged Nrf2-mediated gene expression and protection from superoxide-induced damage
    Petra Bergström
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Institute of Biomedicine, University of Gothenburg, Bruna Straket 16, SE 413 45 Gothenburg, Sweden
    Neuropharmacology 60:343-53. 2011
    ..The findings also demonstrate that part of this response can be built up by repeated transient stimulation, possibly explaining how intermittent intake of sulforaphane can result in long-term protection from radical-induced disease...
  12. pmc Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: restoring effects of inhibitors of HDACs, p38 MAPK and GSK3β
    Fernando Correa
    Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Sweden
    Neurobiol Dis 44:142-51. 2011
    ..In conclusion, the study shows that well tolerated drugs such as VPA and lithium can restore an inflammatory induced depression in the Nrf2-inducible antioxidant defence, possibly via normalised histone acetylation levels...
  13. doi Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone
    Heléne C Andersson
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Medicinaregatan 11, Box 432, SE 40530 Gothenburg, Sweden
    Neurol Res 33:614-24. 2011
    ....
  14. doi Cardiovascular fitness in males at age 18 and risk of serious depression in adulthood: Swedish prospective population-based study
    Maria A I Aberg
    Center for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology and Department of Primary Health Care, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Br J Psychiatry 201:352-9. 2012
    ..Studies suggest a role for cardiovascular fitness in the prevention of affective disorders...
  15. pmc Dual TNFα-induced effects on NRF2 mediated antioxidant defence in astrocyte-rich cultures: role of protein kinase activation
    Fernando Correa
    Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, PO Box 420, 405 30 Goteborg, Sweden
    Neurochem Res 37:2842-55. 2012
    ..One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNFα is detrimental...
  16. doi Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion
    Yolanda de Pablo
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 9A, Gothenburg, 413 90, Sweden
    Histochem Cell Biol 140:81-91. 2013
    ..We conclude that the astrocyte intermediate filament system is important for the cell response to oxidative stress induced by OGD followed by reperfusion. ..
  17. pmc The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK
    Fernando Correa
    Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Sweden
    Glia 59:785-99. 2011
    ..A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2...
  18. pmc Enhanced glutathione efflux from astrocytes in culture by low extracellular Ca2+ and curcumin
    Malin H Stridh
    Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    Neurochem Res 35:1231-8. 2010
    ..The results show that elevated cellular GSH by curcumin treatment enhance efflux from astroglial cells, a process which appear to be a prerequisite for astroglial mediated neuroprotection...
  19. doi Cardiovascular fitness and later risk of epilepsy: a Swedish population-based cohort study
    Jenny Nyberg
    From the Center for Brain Repair and Rehabilitation J N, M A I Å, M N, E B M, H G K, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg Occupational and Environmental Medicine K T, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden and Hunter Medical Research Institute M N, University of Newcastle, Australia
    Neurology 81:1051-7. 2013
    ..To analyze the associations between cardiovascular fitness at age 18 years and future risk of epilepsy...
  20. pmc Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia
    Changlian Zhu
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Goteborg University, 405 30 Goteborg, Sweden
    J Exp Med 204:1741-8. 2007
    ....
  21. ncbi A mapping study on physical activity in stroke rehabilitation: establishing the baseline
    Monica Skarin
    Institute of Neuroscience and Physiology, University of Gothenburg, Per Dubbsg 14, SE 41345 Göteborg E mail
    J Rehabil Med 45:997-1003. 2013
    ..To establish physical activity level, environment and social interaction in routine stroke rehabilitation practice...
  22. ncbi Pituitary function and functional outcome in adults after severe traumatic brain injury: the long-term perspective
    Trandur Ulfarsson
    Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    J Neurotrauma 30:271-80. 2013
    ..Therefore, screening for PTHP might be restricted to specific subgroups such as overweight patients, indicating growth hormone deficiency...
  23. doi Long-term stimulation of neural progenitor cell migration after cortical ischemia in mice
    Ahmed M Osman
    Center for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology, University of Gothenburg, and Sahlgrenska University Hospital, Box 432, S 40530 Gothenburg, Sweden
    Stroke 42:3559-65. 2011
    ..Cortical ischemia induces neural progenitor cell migration toward the injury site; however, whether these cells are capable of maintaining the migratory response for a longer period after injury remains uncertain...
  24. doi A history of unemployment or sick leave influences long-term functioning and health-related quality-of-life after severe traumatic brain injury
    Trandur Ulfarsson
    Center for Brain Repair and Rehabilitation CBR, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    Brain Inj 28:328-35. 2014
    ..This study aimed to determine whether being unemployed or on sick leave before injury influences long-term health-related quality-of-life (HRQoL) and functioning in patients with severe traumatic brain injury...
  25. ncbi Glutathione monoethyl ester provides neuroprotection in a rat model of stroke
    Michelle F Anderson
    Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden
    Neurosci Lett 354:163-5. 2004
    ..Infarct size was reduced from 46% of the total ischaemic hemisphere in saline-treated animals to 16% following ester treatment. Thus, glutathione monoethyl ester provides neuroprotection following transient focal cerebral ischaemia...
  26. ncbi Astrocyte activation and reactive gliosis
    Milos Pekny
    The Arvid Carlsson Institute for Neuroscience, Institute of Clinical Neuroscience, Sahlgrenska Academy at Goteborg University, Goteborg, Sweden
    Glia 50:427-34. 2005
    ....
  27. pmc A systematic review and meta-analysis of erythropoietin in experimental stroke
    Mikael Jerndal
    Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    J Cereb Blood Flow Metab 30:961-8. 2010
    ..As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works best would be beneficial...
  28. ncbi Protective role of reactive astrocytes in brain ischemia
    Lizhen Li
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology at Sahlgrenska Academy, Goteborg University, Goteborg, Sweden
    J Cereb Blood Flow Metab 28:468-81. 2008
    ..Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET(B)R-mediated control of gap junctions, and PAI-1 expression...
  29. ncbi Less neurogenesis and inflammation in the immature than in the juvenile brain after cerebral hypoxia-ischemia
    Lin Qiu
    Institute of Neuroscience and Physiology, Goteborg University, Goteborg, Sweden
    J Cereb Blood Flow Metab 27:785-94. 2007
    ..In summary, contrary to what has been generally assumed, our results indicate that the juvenile brain has a greater capacity for neurogenesis after injury than the immature brain...
  30. pmc The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial
    Lina Bunketorp Käll
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
    BMC Neurol 12:141. 2012
    ..Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted...
  31. doi Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis
    Petra Bergström
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
    Amyotroph Lateral Scler Frontotemporal Degener 15:130-7. 2014
    ..008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis...
  32. ncbi Gap junction blockage limits intercellular spreading of astrocytic apoptosis induced by metabolic depression
    Christina Nodin
    Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience, Goteborg University, Sweden
    J Neurochem 94:1111-23. 2005
    ..The results show that inhibition of gap junctions during cellular metabolic depression interferes with the metabolic status and cell death progression in astrocytes...
  33. doi Lack of association between genetic variations in the KALRN region and ischemic stroke
    Sandra Olsson
    Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden
    Clin Biochem 44:1018-20. 2011
    ..To investigate whether KALRN gene variation is associated with ischemic stroke (IS)...
  34. pmc Cardiovascular fitness is associated with cognition in young adulthood
    Maria A I Aberg
    Center for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE 405 30 Gothenburg, Sweden
    Proc Natl Acad Sci U S A 106:20906-11. 2009
    ..These data substantiate that physical exercise could be an important instrument for public health initiatives to optimize educational achievements, cognitive performance, as well as disease prevention at the society level...
  35. doi 'Better wear out sheets than shoes': a survey of 202 stroke professionals' early mobilisation practices and concerns
    Monica Skarin
    Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Goteborg, Sweden
    Int J Stroke 6:10-5. 2011
    ..This study aims to examine different health professionals' concerns regarding early mobilisation in acute stroke. In this study, early mobilisation was defined as frequent out of bed activities within the first 24 h after stroke onset...
  36. doi Sick leave after traumatic brain injury. The person or the diagnosis--which has greater impact?
    Jerry Larsson
    Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
    Scand J Public Health 38:541-7. 2010
    ..The aim of this study was to describe if and when a sample of traumatic brain injury (TBI) patients could finish their time of sick leave during a 4-year follow up and to explore which factors that influenced the time for sick leave...
  37. ncbi Astrocytes and stroke: networking for survival?
    Michelle F Anderson
    Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden
    Neurochem Res 28:293-305. 2003
    ..A detailed understanding of the astrocytic response, as well as the timing and location of the changes, is necessary to develop effective treatment strategies for stroke patients...
  38. ncbi Insulin-like growth factor-I and neurogenesis in the adult mammalian brain
    Michelle F Anderson
    Institute of Clinical Neuroscience, Goteborg University, Bla straket 7, Goteborg, Sweden
    Brain Res Dev Brain Res 134:115-22. 2002
    ..Thus, there is a tight correlation between IGF-I and neurogenesis in the adult brain under different conditions. Further studies are needed to clarify whether IGF-I does indeed mediate neurogenesis in these situations...
  39. ncbi Mitochondrial glutathione protects against cell death induced by oxidative and nitrative stress in astrocytes
    Hakan Muyderman
    Centre for Neuroscience and Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia
    J Neurochem 102:1369-82. 2007
    ....
  40. ncbi [Neurobiology provides a scientific foundation for rehabilitation. Report from an international symposium]
    Gunnar Grimby
    Sahlgrenska Universitetssjukhuset, Goteborg
    Lakartidningen 100:2052-5. 2003
    ..Knowledge about modulation of pain signals within the central nervous system will increase the therapeutic possibilities at long-standing pain, for example, concerning increased sensitivity and impaired inhibition...
  41. ncbi Fluorocitrate-mediated astroglial dysfunction causes seizures
    John O Willoughby
    Centre for Neuroscience and Department of Medicine, Flinders University and Medical Centre, Adelaide, South Australia, Australia
    J Neurosci Res 74:160-6. 2003
    ..These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive seizures and that the process possibly depends on effects mediated by gap junctions...
  42. ncbi Reloading the retina by modifying the glial matrix
    Roy Quinlan
    School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, UK
    Trends Neurosci 27:241-2. 2004
    ....
  43. ncbi Highly selective and prolonged depletion of mitochondrial glutathione in astrocytes markedly increases sensitivity to peroxynitrite
    Hakan Muyderman
    Centre for Neuroscience, Flinders Institute for Health and Medical Research, and Department of Medical Biochemistry, School of Medicine, Flinders University, 5001 Adelaide, SA, Australia
    J Neurosci 24:8019-28. 2004
    ..They demonstrate the critical importance of this metabolite pool in protecting against peroxynitrite-induced damage in astrocytes and indicate a key contribution in determining the activities of respiratory chain components...
  44. ncbi Astrocytic function assessed from 1-14C-acetate metabolism after temporary focal cerebral ischemia in rats
    Anna E Thoren
    Centre for Neuroscience and Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia
    J Cereb Blood Flow Metab 25:440-50. 2005
    ..These results indicate that many astrocytes, particularly in the cortex, remain viable and capable of at least some complex oxidative metabolism during the first few hours of recirculation...
  45. ncbi The metabolism of C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats
    Anna E Thoren
    Centre for Neuroscience and Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia
    J Neurochem 97:968-78. 2006
    ..These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to temporary focal ischemia...