ORCID Profile
0000-0002-6027-2089
Current Organisations
University of Helsinki
,
University of Sussex
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Publisher: Wiley
Date: 04-12-2014
DOI: 10.1002/CJP2.3
Publisher: Oxford University Press (OUP)
Date: 13-06-2014
DOI: 10.1093/HMG/DDU300
Publisher: Oxford University Press (OUP)
Date: 06-2002
Abstract: Mutations of survival of the motor neuron gene (SMN1) are responsible for spinal muscular atrophy (SMA), a common genetic cause of death in childhood. The cellular mechanism by which mutations of SMN1 are responsible for the selective neuromuscular defect and motor neuron cell degeneration observed in SMA has not been described. We have previously generated mice carrying a homozygous deletion of Smn exon 7 directed to neurons. We report here that these mutant mice display a dramatic and progressive loss of motor axons involving both proximal and terminal regions, in agreement with the skeletal muscle denervation process and disease progression. Moreover, we found massive accumulation of neurofilaments, including phosphorylated forms, in terminal axons of the remaining neuromuscular junctions. This aberrant cytoskeletal organization of synaptic terminals was associated with reduction of branched structures of the postsynaptic apparatus and defect of axonal sprouting in mutant mice. Together, these findings may be responsible for severe motor neuron dysfunction, and suggest that loss of motor neuron cell bodies results from a 'dying-back' axonopathy in SMA. Smn mutant mice should represent a valuable model for elucidating the pathway linking Smn to cytoskeletal organization.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2007
DOI: 10.1038/NATURE05887
Publisher: Springer Science and Business Media LLC
Date: 09-03-2015
DOI: 10.1038/NG.3242
Publisher: Wiley
Date: 09-11-2009
DOI: 10.1002/RCM.4291
Abstract: Recent advances in phosphoproteomics have established powerful tools to analyze phosphorylation events. However, their spatial localization is lost due to s le homogenization procedures prior to the analysis. Imaging mass spectrometry (IMS) has emerged as a method to visualize the spatial distribution of molecules in tissue s les, but its application is still limited to relatively abundant molecules. Due to low phosphorylation stoichiometry, direct detection and imaging of protein phosphorylation by MS has not been achieved yet. Therefore we have developed a novel phosphopeptide enrichment strategy as a potential tool for in situ affinity imaging MS (AIMS). A specific type of titanium dioxide (TiO2)-coated glass slides was designed and validated with casein tryptic digests for their ability to selectively retain phosphopeptides while maintaining their spatial coordination.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.EJCA.2007.04.021
Abstract: Little is known regarding cancer clinicians' treatment preferences. Determine the impact of pre-operative variables over specialist breast clinicians' operative preferences using discrete choice experiment methodology. Cross-sectional survey of operative preferences to hypothetical scenarios based on: patient age, bra cup size, cancer size, site and focality. 73% response rate (68/93). Multinomial logistic regression across scenarios (n=1695) with allowance for response clustering, comparing equal preference for mastectomy and breast conservation surgery (BCS) with preference for mastectomy or BCS. Increasing patient age, cancer size, central site, multi-focality and reducing cup size, all associated with preference for mastectomy, over equal preference, over BCS (p<0.001). Doctors preferred specific treatments, females and nurses avoided mastectomy (p=0.015 and p<0.001 respectively). Clinician preferences were predominantly treatment guideline congruent, but significantly influenced by patient age, clinician gender and occupation. This methodology is capable of elucidating treatment preferences and could be applied elsewhere where treatment options and practice variability exist.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mikko Heikkilä.