22 results on '"Ulla Lahtinen"'
Search Results
2. NAFOL Yearbook 2012
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Gert Biesta, Inga Bostad, Lars Løvlie, Petter Aasen, Lee S. Shulman, Stella Damaris Ngorosho, Ulla Lahtinen, Marilyn Cochran-Smith, Franziska Frost, Tina Seidel, Manfred Prenzel, Kristin Helstad, Andreas Lund, Kristin Barstad, Siv Saarukka, Solveig Åsgard Bendiksen, Dag Ofstad, Camilla Cederholm, Alex Strømme, Johanna Ray, and Hannah Kaihovirta-Rosvik
- Abstract
Some of the main goals that education strives to achieve are certification and socialization. To achieve these goals in the best interest of the individual and society is a demanding challenge for all involved. In what context is the certification going to be used? Into what society are those educated expected to socialize? Teacher education is at the heart of the discussion as it is responsible for educating teachers whose task it will be to certify and socialize a new generation into a society, the nature of which is, to a large extent, still unknown. The aim of the NAFOL Year Book 2012 is to contribute to research-based knowledge in teacher education. The anthology consists of contributions from lecturers, invited guest professors, key note speakers, and PhD students in some way connected to the national graduate school for teacher education NAFOL during 2012. The anthology is thought of as an innovation combining the characteristics of a yearbook of a journal and the characteristics of a conference anthology.
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- 2022
3. Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd: implications to delayed myelination and oligodendrocyte maturation
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Martin Hermansson, Olli Gröhn, Pentti Somerharju, M. Eckhardt, Ulla Lahtinen, M. Talvitie, I. Zech, Anna-Elina Lehesjoki, Jonathan D. Cooper, Otto Manninen, Outi Kopra, Mervi Kuronen, and Teemu Laitinen
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0303 health sciences ,Histology ,Batten disease ,Galactolipid ,Lipid metabolism ,Biology ,medicine.disease ,Oligodendrocyte ,3. Good health ,Pathology and Forensic Medicine ,Cell biology ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine.anatomical_structure ,Neurology ,Biochemistry ,CLN8 ,Physiology (medical) ,medicine ,Neuroglia ,Neuronal ceroid lipofuscinosis ,Neurology (clinical) ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
M. Kuronen, M. Hermansson, O. Manninen, I. Zech, M. Talvitie, T. Laitinen, O. Grohn, P. Somerharju, M. Eckhardt, J. D. Cooper, A.-E. Lehesjoki, U. Lahtinen and O. Kopra (2012) Neuropathology and Applied Neurobiology38, 471–486 Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd: implications to delayed myelination and oligodendrocyte maturation Aims: CLN8 deficiency underlies one of a group of devastating childhood neurodegenerative disorders, the neuronal ceroid lipofuscinoses. The function of the CLN8 protein is currently unknown, but a role in lipid metabolism has been proposed. In human CLN8 diseased brains, alterations in lipid composition have been detected. To further investigate the connection of CLN8 to lipid metabolism, we characterized the lipid composition of early symptomatic Cln8-deficient mouse (Cln8mnd) brains. Methods: For lipid profiling, Cln8mnd cerebral cortical tissue was analysed by liquid chromatography/mass spectrometry. Galactolipid synthesis was measured through enzyme activity and real-time mRNA expression analyses. Based on the findings, myelination and white matter integrity were studied by immunohistochemistry, stereological methods, electron microscopy and magnetic resonance imaging. The development of myelin-forming oligodendrocytes was also studied in vitro. Results: Sphingolipid profiling showed a selective reduction in myelin-enriched galactolipids. The mRNA expression and activity of UDP-galactose:ceramide galactosyltransferase (CGT), the key enzyme in the galactolipid synthesis, was reduced in the Cln8mnd brain. Expression of oligodendrocyte markers suggests a maturation defect. The amount of myelin was reduced in 1-month-old Cln8mnd mice, but reached normal levels by 5 months of age. The level of Cln8 gene expression followed the developmental pattern of myelin formation and was high in primary oligodendrocytes. Conclusions: Taken together, these observations suggest that galactolipid deficiency and delayed myelin maturation characterize the early CLN8 disease pathogenesis through a maturation defect of oligodendrocytes.
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- 2012
4. The Effect of Nitrazepam on Manual Skill, Grip Strength, and Reaction Time with Special Reference to Subjective Evaluation of Effects on Sleep
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Ulla Lahtinen, Antti Lahtinen, and Pentti Pekkola
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Adult ,Injury control ,Nitrazepam ,medicine.drug_class ,Accident prevention ,Poison control ,Motor Activity ,Toxicology ,behavioral disciplines and activities ,Hypnotic ,Grip strength ,Reaction Time ,medicine ,Humans ,Ingestion ,Pharmacology ,Psychomotor learning ,Clinical Trials as Topic ,business.industry ,Motor Skills ,Anesthesia ,Drug Evaluation ,Female ,Sleep ,business ,Muscle Contraction ,medicine.drug - Abstract
The effects of 5 and 10 mg oral nitrazepam doses on manual skills, grip strength, and reaction time 8 hours after ingestion of the drugs were studied in 34 healthy female volunteers aged 19-22 years. 5 mg nitrazepam caused a slight but insignificant decrease in psychomotor skills. With 10 mg psychomotor skills were influenced significantly. Grip strength and reaction time were not influenced either by the 5 or 10 mg doses. The investigators corroborate the value of the established effects of nitrazepam as a hypnotic, but recommend that caution should be excercised in prescribing the drug as a hypnotic (especially in doses exceeding 5 mg) to work-aged subjects as there is a risk of significant effect on the psychomotor skills. Furthermore, the drug may cause fatigue. Language: en
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- 2009
5. The Novel Neuronal Ceroid Lipofuscinosis Gene MFSD8 Encodes a Putative Lysosomal Transporter
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Eija Siintola, Nina Aula, Hannes Lohi, Xiao-Qing Liu, Meral Topçu, Ulla Lahtinen, Callum Wilson, Anna-Kaisa Anttonen, Andrew D. Paterson, Berge A. Minassian, Anna-Elina Lehesjoki, and Çocuk Sağlığı ve Hastalıkları
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Adult ,Male ,Adolescent ,Turkey ,DNA Mutational Analysis ,Molecular Sequence Data ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neuronal Ceroid-Lipofuscinoses ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Amino Acid Sequence ,RNA, Messenger ,Child ,Gene ,Conserved Sequence ,Genetics (clinical) ,030304 developmental biology ,Genetics & Heredity ,0303 health sciences ,Genetic heterogeneity ,Homozygote ,Alternative splicing ,Membrane Transport Proteins ,Disease gene identification ,medicine.disease ,Pedigree ,3. Good health ,Alternative Splicing ,Membrane protein ,CLN8 ,Child, Preschool ,Mutation ,Female ,Neuronal ceroid lipofuscinosis ,Lysosomes ,030217 neurology & neurosurgery - Abstract
The late-infantile-onset forms are the most genetically heterogeneous group among the autosomal recessively inherited neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). The Turkish variant was initially considered to be a distinct genetic entity, with clinical presentation similar to that of other forms of late- infantile-onset NCL (LINCL), including age at onset from 2 to 7 years, epileptic seizures, psychomotor deterioration, myoclonus, loss of vision, and premature death. However, Turkish variant LINCL was recently found to be genetically heterogeneous, because mutations in two genes, CLN6 and CLN8, were identified to underlie the disease phenotype in a subset of patients. After a genomewide scan with single-nucleotide-polymorphism markers and homozygosity mapping in nine Turkish families and one Indian family, not linked to any of the known NCL loci, we mapped a novel variant LINCL locus to chromosome 4q28.1-q28.2 in five families. We identified six different mutations in the MFSD8 gene ( previously denoted "MGC33302"), which encodes a novel polytopic 518-amino acid membrane protein that belongs to the major facilitator superfamily of transporter proteins. MFSD8 is expressed ubiquitously, with several alternatively spliced variants. Like the majority of the previously identified NCL proteins, MFSD8 localizes mainly to the lysosomal compartment. However, the function of MFSD8 remains to be elucidated. Analysis of the genome-scan data suggests the existence of at least three more genes in the remaining five families, further corroborating the great genetic heterogeneity of LINCLs.
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- 2007
6. Functional biology of the neuronal ceroid lipofuscinoses (NCL) proteins
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Ulla Lahtinen, Aija Kyttälä, Sandra L. Hofmann, and Thomas Braulke
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Batten disease ,Endosome ,ved/biology.organism_classification_rank.species ,Biology ,medicine.disease_cause ,Aminopeptidases ,Lipofuscin ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neuronal Ceroid-Lipofuscinoses ,Endopeptidases ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Neurodegeneration ,Model organism ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Mutation ,Membrane Glycoproteins ,Tripeptidyl-Peptidase 1 ,ved/biology ,Infant ,Lysosome-Associated Membrane Glycoproteins ,Membrane Proteins ,NCL ,medicine.disease ,Cathepsins ,Transmembrane protein ,Lysosomal degradation ,Biochemistry ,Storage disease ,Molecular Medicine ,Thiolester Hydrolases ,Serine Proteases ,Neuroscience ,030217 neurology & neurosurgery ,Function (biology) ,Molecular Chaperones - Abstract
Neuronal ceroid lipofucinoses (NCLs) are a group of severe neurodegenerative disorders characterized by accumulation of autofluorescent ceroid lipopigment in patients' cells. The different forms of NCL share many similar pathological features but result from mutations in different genes. The genes affected in NCLs encode both soluble and transmembrane proteins and are localized to ER or to the endosomes/lysosomes. Due to selective vulnerability of the central nervous system in the NCL disorders, the corresponding proteins are proposed to have important, tissue specific roles in the brain. The pathological similarities of the different NCLs have led not only to the grouping of these disorders but also to suggestion that the NCL proteins function in the same biological pathway. Despite extensive research, including the development of several model organisms for NCLs and establishment of high-throughput techniques, the precise biological function of many of the NCL proteins has remained elusive. The aim of this review is to summarize the current knowledge of the functions, or proposed functions, of the different NCL proteins.
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- 2006
- Full Text
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7. The role of the home environment in phonological awareness and reading and writing ability in Tanzanian primary schoolchildren
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Ulla Lahtinen and Damaris Ngorosho
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Public Administration ,Sociology and Political Science ,biology ,media_common.quotation_subject ,School library ,biology.organism_classification ,Educational attainment ,Education ,Developmental psychology ,Tanzania ,Phonological awareness ,Reading (process) ,Family literacy ,home environment, phonological awareness, reading and writing ability, Kiswahili, transparent orthography, Tanzania ,Psychology ,Socioeconomic status ,Orthography ,media_common - Abstract
In developing countries, the role of the home environment in children’s development of literacy skills is largely unknown. This study examines the relationship in a sample of 75 grade two children from rural eastern Tanzania. It also discusses the role of house building material and domestic facilities, in addition to parents’ education and occupation, in describing socioeconomic status in developing countries in general, and in the current study. Most of the factors were significantly (ANOVA) related to phonological awareness and reading and writing. Hierarchical multiple regression analysis identified fathers’ education and mothers’ occupation as strong predictors. The home environment variables accounted for 25% of the variance in phonological awareness and 19% in reading and writing ability. Early screening and support of children in the risk zone of becoming poor readers are proposed. Activities like children’s book projects and school library facilities are suggested, aiming at supporting literacy-related activities in low capacity homes. Keywords: home environment, phonological awareness, reading and writing ability, Kiswahili, transparent orthography, Tanzania (Published: 1 September 2010) Citation: Education Inquiry Vol. 1, No. 3, September 2010, pp.211–234
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- 2010
8. Characterization of a 58 kDa cis-Golgi protein in pancreatic exocrine cells
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B. Dahllof, Jaakko Saraste, and Ulla Lahtinen
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Glycosylation ,Protein Conformation ,Golgi Apparatus ,Biology ,Endoplasmic Reticulum ,chemistry.chemical_compound ,symbols.namesake ,Acinus ,Microsomes ,Tumor Cells, Cultured ,medicine ,Animals ,Secretion ,Microscopy, Immunoelectron ,Pancreas ,Secretory pathway ,Endoplasmic reticulum ,Membrane Proteins ,Cell Biology ,Golgi apparatus ,Rats ,Molecular Weight ,medicine.anatomical_structure ,Biochemistry ,chemistry ,Biophysics ,symbols ,Microsome ,Cell fractionation ,Subcellular Fractions - Abstract
We have studied the biochemical characteristics and localization of a 58 kDa cis-Golgi marker protein (p58) in rat pancreatic exocrine cells. The protein remained associated with membranes after extraction at alkaline pH and was largely resistant to proteases, added to intact microsomes. By electrophoresis p58 could be resolved into two bands which in two-dimensional gels separated into several charge variants around pI 5.5. This size and charge heterogeneity of p58 did not appear to be due to acylation, glycosylation or phosphorylation. In non-reduced gels p58 migrated as two kinetically related, high relative molecular mass forms, apparently corresponding to disulfide-linked homo-dimers and -hexamers. Immuno-electron microscopy localized p58 to both the fenestrated cis-Golgi cisternae and small Golgi vesicles or buds as well as large, pleiomorphic structures, scattered throughout the cells and associated with distinct smooth ER (endoplasmic reticulum) clusters. These findings correlated with cell fractionation results showing the concentration of p58 in two microsomal subfractions, banding at intermediate densities between the rough ER and trans-Golgi in sucrose gradients. Our results indicate that p58 is a major component of pre- and cis-Golgi elements and could be part of the transport machinery that operates in these membranes. Together with results obtained with other cell types, these observations suggest that the peripheral smooth ER clusters are involved in the early stages of the secretory pathway in the pancreatic acinar cells.
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- 1992
9. Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia
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Tero Kivelä, Mirja Somer, Christine M. Laine, Sanna-Maria Toiviainen-Salo, Ulla Lahtinen, Outi Mäkitie, Tero Saukkonen, Anna-Elina Lehesjoki, William G. Cole, and A. Saarinen
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Hypercholesterolemia ,Molecular Sequence Data ,030209 endocrinology & metabolism ,Biology ,Compound heterozygosity ,Impaired glucose tolerance ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Bone Density ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,medicine ,Glucose homeostasis ,Humans ,Amino Acid Sequence ,LDL-Receptor Related Proteins ,030304 developmental biology ,Aged ,0303 health sciences ,Lumbar Vertebrae ,Femur Neck ,LRP5 ,Lipid metabolism ,Glioma ,Syndrome ,Middle Aged ,medicine.disease ,Lipid Metabolism ,3. Good health ,Low Density Lipoprotein Receptor-Related Protein-5 ,Mutation ,Female - Abstract
OBJECTIVE Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) underlie osteoporosis-pseudoglioma syndrome. Animal models implicate a role for LRP5 in lipid and glucose homeostasis. The objective was to evaluate metabolic consequences of LRP5 mutations in humans. DESIGN AND PATIENTS Thirteen Finnish individuals with homozygous or heterozygous LRP5 mutations were assessed for bone health, glucose and lipid metabolism, and for serum serotonin concentration. Results were compared with findings in family members without mutations. MEASUREMENTS Bone mineral density (BMD), vertebral morphology, oral and intravenous glucose tolerance tests, lipid profile and serum serotonin concentrations. RESULTS Two individuals were homozygous for R570W, one compound heterozygous for R570W and R1036Q, and 10 were heterozygous (six for R570W, three for R1036Q and one for R925C). Subjects with two LRP5 mutations had multiple spinal fractures and low BMD. Subjects with one mutation had significantly lower median lumbar spine (P = 0.004) and femoral neck (P = 0.005) BMD Z-scores, and more often vertebral fractures than the 18 individuals without mutations. Of the 12 subjects with LRP5 mutation six had diabetes and one had impaired glucose tolerance. Intravenous glucose tolerance tests suggested impaired beta-cell function; no insulin resistance was observed. Prevalence of hypercholesterolaemia was similar in mutation positive and negative subjects. Serum serotonin concentrations showed a trend towards higher concentrations in subjects with LRP5 mutation. CONCLUSIONS We found high prevalence of osteoporosis and abnormal glucose metabolism in subjects with LRP5 mutation(s). Further studies are needed to establish the role of LRP5 in glucose and lipid metabolism.
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- 2009
10. The effect of conventional movement training and trampoline training on balance and gait in chronic hemiplegic patients
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Pertti Era, Aini Konttinen, Oili Harri-Lehtonen, and Ulla Lahtinen
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medicine.medical_specialty ,business.industry ,Movement (music) ,05 social sciences ,Training (meteorology) ,050401 social sciences methods ,Physical Therapy, Sports Therapy and Rehabilitation ,Gait ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,0504 sociology ,Walking velocity ,Physical therapy ,Medicine ,Trampoline ,business ,human activities ,Eyes open ,Training programme ,030217 neurology & neurosurgery ,Balance (ability) - Abstract
The postural sway of subjects during standing both with their eyes open and closed together with maximum velocity of walking were analysed in six male chronic hemiplegic patients before, during and after an intensive movement training programme lasting 8 weeks. The movement training programme was carried out on the basis of Bobath's principles. Three of the subjects carried out their training on a trampoline, with the particular purpose of enhancing the stimulation of the mechanisms responsible for the control of balance. During the follow-up, maximal walking velocity remained at previous levels and no systematic changes were observed in the control of postural sway. Although the use of the trampoline did not indicate special advantages for the balance or gait of these patients, its use in movement training is nevertheless encouraged as an alternative and motivational factor that might also lead to specific benefits with a training programme of longer duration.
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- 1991
11. Physical performance of individuals with intellectual disability: a 30 year follow up
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Pauli Rintala, Antero Malin, and Ulla Lahtinen
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Gerontology ,Adult ,Male ,Down syndrome ,medicine.medical_specialty ,Adolescent ,Physical fitness ,Persons with Mental Disabilities ,Physical Therapy, Sports Therapy and Rehabilitation ,Overweight ,Body Mass Index ,Sex Factors ,Intellectual Disability ,Intellectual disability ,medicine ,Humans ,Longitudinal Studies ,Muscle Strength ,Young adult ,Child ,Postural Balance ,Finland ,Psychomotor learning ,Intelligence quotient ,business.industry ,Age Factors ,Middle Aged ,medicine.disease ,Physical Fitness ,Case-Control Studies ,Physical therapy ,Physical Endurance ,Female ,medicine.symptom ,Psychology ,business ,Body mass index ,Psychomotor Performance - Abstract
Physical performance of Finnish adolescents (33 females, 44 males) with moderate intellectual disability (ID) was studied over a 30-year period. This study is an extension of Lahtinen’s previous work on documenting the performance of individuals with intellectual disabilities over time. This study consisted of analyzing data from a total of four data collection periods (1973, 1979, 1996, and 2003 in which participants ranged in age from 11-16, 17-22, 34-39 and 41-46 years old, respectively). Improvement from early to late adolescence, and decline during adulthood in abdominal strength/endurance, static balance, and manual dexterity were identified. The male adults with ID were moderately overweight (BMI), but the females with ID were obese. The IQ effect was significant on balance and manual dexterity. The gender differences in adulthood were significant, but differences were not noted for Down syndrome when controlling for IQ.
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- 2007
12. Oligomerization and interacellular localization of the glycoprotein receptor ERGIC-53 is independent of disulfide bonds
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Ulla Lahtinen, Etienne P. A. Neve, and Ralf F. Pettersson
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Electrophoresis ,Protein Denaturation ,Mutant ,Vesicular Transport Proteins ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Centrifugation, Density Gradient ,Humans ,Cysteine ,Disulfides ,Protein Structure, Quaternary ,Molecular Biology ,030304 developmental biology ,Glycoproteins ,chemistry.chemical_classification ,Gel electrophoresis ,0303 health sciences ,Chemistry ,Endoplasmic reticulum ,Cell Membrane ,Membrane Proteins ,Transmembrane protein ,Transmembrane domain ,Protein Transport ,Cross-Linking Reagents ,Mannose-Binding Lectins ,Biochemistry ,030220 oncology & carcinogenesis ,Mutation ,Cell fractionation ,Glycoprotein ,Carrier Proteins ,Dimerization ,HeLa Cells ,Protein Binding - Abstract
ERGIC-53 is a type I transmembrane lectin facilitating the efficient export of a subset of secretory glycoproteins from the endoplasmic reticulum. Previous results have shown that ERGIC-53 is present as reduction-sensitive homo-oligomers, i.e. as a balanced mixture of disulfide-linked hexamers and dimers, with the two cysteine residues located close to the transmembrane domain playing a crucial role in oligomerization. Here, we demonstrate, using sucrose gradient sedimentation, cross-linking analyses, and non-denaturing gel electrophoresis, that ERGIC-53 is present exclusively as a hexameric complex in cells. However, the hexamers exist in two forms, one as a disulfide-linked, Triton X-100, perfluoro-octanic acid, and SDS-resistant complex, and the other as a non-covalent, Triton X-100, perfluoro-octanoic acid-resistant, but SDS-sensitive, complex made up of three disulfide-linked dimers that are likely to interact through the coiled-coil domains present in the luminal part of the protein. In contrast to what was previously believed, neither of the membrane-proximal cysteine residues plays an essential role in the formation, or maintenance, of the latter form of hexamers. Subcellular fractionation revealed that the double-cysteine mutant was present in the endoplasmic reticulum-Golgi-intermediate compartment, indicating that the two cysteine residues are not essential for the intracellular distribution of ERGIC-53. Based on these results, we present a model for the formation of the two hexameric forms.
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- 2005
13. Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations
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Dick Lindhout, Anna-Elina Lehesjoki, Ekkehard Weber, Paula Salmikangas, Pekka Saukko, Gerit Theil, Ulla Lahtinen, Kirsi Alakurtti, Riitta Rinne, and Gerrit-Jan de Haan
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Cytoplasm ,Muscle Fibers, Skeletal ,Mutation, Missense ,Progressive myoclonus epilepsy ,Minisatellite Repeats ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Mutant protein ,Cricetinae ,Genetics ,medicine ,Missense mutation ,Animals ,Humans ,Cystatin B ,RNA, Messenger ,Promoter Regions, Genetic ,Gene ,Genetics (clinical) ,030304 developmental biology ,Cathepsin ,Cell Nucleus ,0303 health sciences ,Mutation ,Cell Differentiation ,medicine.disease ,Myoclonic Epilepsies, Progressive ,Molecular biology ,Cystatins ,Protein Transport ,COS Cells ,Lysosomes ,030217 neurology & neurosurgery - Abstract
Loss-of-function mutations in the cystatin B (CSTB), a cysteine protease inhibitor, gene underlie progressive myoclonus epilepsy of Unverricht–Lundborg type (EPM1), characterized by myoclonic and tonic–clonic seizures, ataxia and a progressive course. A minisatellite repeat expansion in the promoter region of the CSTB gene is the most common mutation in EPM1 patients and leads to reduced mRNA levels. Seven other mutations altering the structure of CSTB, or predicting altered splicing, have been described. Using a novel monoclonal CSTB antibody and organelle-specific markers in human primary myoblasts, we show here that endogenous CSTB localizes not only to the nucleus and cytoplasm but also associates with lysosomes. Upon differentiation to myotubes, CSTB becomes excluded from the nucleus and lysosomes, suggesting that the subcellular distribution of CSTB is dependent on the differentiation status of the cell. Four patient mutations altering the CSTB polypeptide were transiently expressed in BHK-21 cells. The p.Lys73fsX2-truncated mutant protein shows diffuse cytoplasmic and nuclear distribution, whereas p.Arg68X is rapidly degraded. Two missense mutations, the previously described p.Gly4Arg affecting the highly conserved glycine, critical for cathepsin binding, and a novel mutation, p.Gln71Pro, fail to associate with lysosomes. These data imply an important lysosome-associated physiological function for CSTB and suggest that loss of this association contributes to the molecular pathogenesis of EPM1.
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- 2004
14. Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes
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Anna-Elina Lehesjoki, Karin Brännvall, Helena Hjelm, Dan Lindholm, Laura Korhonen, and Ulla Lahtinen
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DNA, Complementary ,Biophysics ,Gene Expression ,Hippocampal formation ,Biology ,medicine.disease_cause ,Biochemistry ,Hippocampus ,Mice ,medicine ,Animals ,Humans ,Cystatin B ,Molecular Biology ,reproductive and urinary physiology ,Cells, Cultured ,Neurons ,Mutation ,Base Sequence ,Stem Cells ,Cell Differentiation ,Cell Biology ,Myoclonic Epilepsies, Progressive ,Embryonic stem cell ,Cystatins ,Neural stem cell ,nervous system diseases ,Cell biology ,Rats ,Neuroepithelial cell ,medicine.anatomical_structure ,nervous system ,Cytoplasm ,Astrocytes ,Immunology ,Lysosomes ,Nucleus - Abstract
Mutation in the gene encoding cystatin-B (CSTB) has been shown to cause progressive myoclonus epilepsy. Mice with a gene deletion of CSTB exhibit increased apoptosis of specific neurons but the physiological role of CSTB in brain cells is not fully understood. In the present study, we have examined the expression of CSTB in neural stem cells (NSC) and in differentiating mature brain cells. The results show that CSTB is present in embryonic and adult NSC and in the neuroepithelium. CSTB was expressed by both neurons and glial cells differentiated from NSC and in hippocampal cultures. CSTB localized mainly to the nucleus in NSC and in neurons, whilst in astrocytes CSTB was also in the cytoplasm. Double labeling showed that CSTB was present in the lysosomes in glial cells. The results demonstrate a nuclear expression of CSTB in NSC and in neurons, suggesting novel function for this molecule.
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- 2003
15. Expression, purification, refolding and crystallization of the carbohydrate-recognition domain of p58/ERGIC-53, an animal C-type lectin involved in export of glycoproteins from the endoplasmic reticulum
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Ylva Lindqvist, Ulla Lahtinen, Lucas M. Velloso, Ralf F. Pettersson, Kerstin Svensson, and Gunter Schneider
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Protein Folding ,Protein Conformation ,Carbohydrates ,Crystallography, X-Ray ,Endoplasmic Reticulum ,symbols.namesake ,Structural Biology ,C-type lectin ,Lectins ,Animals ,Humans ,Mannan-binding lectin ,Glycoproteins ,biology ,Vesicular-tubular cluster ,Endoplasmic reticulum ,Lectin ,Membrane Proteins ,STIM1 ,General Medicine ,Golgi apparatus ,Transmembrane protein ,Protein Structure, Tertiary ,Rats ,Mannose-Binding Lectins ,Biochemistry ,biology.protein ,symbols ,Crystallization - Abstract
p58/ERGIC-53 is a mammalian calcium-dependent lectin that serves as a glycoprotein-sorting receptor between the endoplasmic reticulum (ER) and the Golgi complex. It is a type I transmembrane protein with two lumenal domains, one of which is a carbohydrate-recognition domain (CRD) and homologous to leguminous lectins. The CRD of p58, the rat homologue of human ERGIC-53, was overexpressed in insect cells and Escherichia coli, purified and crystallized using Li(2)SO(4) as a precipitant. The crystals belong to space group I222, with unit-cell parameters a = 49.6, b = 86.1, c = 128.1 A, and contain one molecule per asymmetric unit, corresponding to a packing density of 2.4 A(3)Da(-1). Knowledge of the structure of p58/ERGIC-53 will provide a starting model for understanding receptor-mediated glycoprotein sorting between the ER and the Golgi.
- Published
- 2001
16. Molecular cloning and expression of a 58-kDa cis-Golgi and intermediate compartment protein
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Jaakko Saraste, Ulf Hellman, Ralf F. Pettersson, Ulla Lahtinen, and Christer Wernstedt
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Signal peptide ,Macromolecular Substances ,Molecular Sequence Data ,Fluorescent Antibody Technique ,Gene Expression ,Golgi Apparatus ,Target peptide ,Biology ,Endoplasmic Reticulum ,Biochemistry ,Antibodies ,Chromatography, Affinity ,symbols.namesake ,Xenopus laevis ,Microsomes ,Animals ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Molecular Biology ,Pancreas ,Secretory pathway ,Base Sequence ,Sequence Homology, Amino Acid ,Endoplasmic reticulum ,Cell Membrane ,Membrane Proteins ,STIM1 ,Cell Biology ,COPI ,Intracellular Membranes ,Golgi apparatus ,Molecular biology ,Recombinant Proteins ,Rats ,Molecular Weight ,Membrane protein ,symbols - Abstract
An abundant 58-kDa (p58) homodimeric and hexameric microsomal membrane protein has been biochemically characterized and localized to tubulo-vesicular elements at the endoplasmic reticulum-Golgi interface and the cis-Golgi cisternae in pancreatic acinar cells (Lahtinen, U., Dahllöf, B., and Saraste, J. (1992) J. Cell Sci. 103, 321-333). Here we report the purification of p58 by two-dimensional gel electrophoresis, and the cloning and sequencing of the rat and part of the Xenopus laevis cDNAs. The rat cDNA encodes a 517-amino acid protein having a putative signal sequence, a transmembrane domain close to the C terminus and a short cytoplasmic tail. The C-terminal tail contains a double-lysine motif (KKFF), known to mediate retrieval of proteins from the Golgi back to the endoplasmic reticulum. The rat p58 sequence was found to be 89% identical with those of ERGIC-53 and MR60, two previously identified human membrane proteins. Strong homology with the frog sequence was also observed indicating high evolutionary conservation. Overexpression of c-Myc-tagged p58 resulted in accumulation of the protein both in the endoplasmic reticulum and in an apparently enlarged Golgi complex, as well as its leakage to the plasma membrane. Immunolocalization using antibodies raised against a lumenal peptide stained the total cellular pool of p58, while anti-tail peptide antibodies detected p58 only in a restricted Golgi region. This suggests that the C-terminal tail of p58 located in the endoplasmic reticulum and transport intermediates is hidden, but becomes exposed when the protein reaches the Golgi complex.
- Published
- 1996
17. Localization of the small GTP-binding protein rab1p to early compartments of the secretory pathway
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Ulla Lahtinen, Jaakko Saraste, and Bruno Goud
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Cell type ,Saccharomyces cerevisiae Proteins ,Fluorescent Antibody Technique ,Golgi Apparatus ,Vacuole ,Biology ,Cell Fractionation ,Endoplasmic Reticulum ,Kidney ,Antibodies ,Cell Line ,GTP Phosphohydrolases ,Immunoenzyme Techniques ,symbols.namesake ,Mice ,GTP-Binding Proteins ,Microsomes ,Animals ,Microscopy, Immunoelectron ,Pancreas ,Secretory pathway ,Organelles ,Endoplasmic reticulum ,Vesicle ,Cell Biology ,Golgi apparatus ,Cell biology ,Rats ,Membrane ,rab GTP-Binding Proteins ,symbols ,Cell fractionation ,Multiple Myeloma ,Biomarkers - Abstract
We have studied the localization of the small GTPase rab1p in different cell types using polyclonal antibodies prepared against the rab1A isoform of the protein. Immunofluorescence microscopy of normal rat kidney (NRK) and mouse myeloma cells showed the association of the protein with the Golgi complex and peripheral sites where it colocalized with p58, a pre- and cis-Golgi marker protein. Rab1p and p58 also had similar distributions in membrane fractions derived from rat pancreas microsomes. Both were concentrated in two intermediate density subfractions between the rough endoplasmic reticulum and trans-Golgi, whereas rab6p, previously localized to middle and trans-Golgi, was enriched in the light density trans-Golgi fraction. Immunoperoxidase electron microscopy of NRK and myeloma cells revealed the association of rab1p with 1–2 cisternae, vacuolar, and tubulovesicular membranes in the cis-Golgi region. The rab1p-specific staining typically covered the entire lateral surface of the cisternae but, in weakly stained cells, local labeling between closely opposed membranes could also be seen. The rab1p-positive pre-Golgi compartment had a predominantly tubulovesicular appearance in NRK cells whereas in myeloma cells it consisted of vacuoles surrounded by rab1p-positive vesicles and tubules of heterogeneous size. In both cell types the rough ER cisternae and the nuclear envelope contained negligible labeling and no continuities between these and the rab1p-positive membranes were observed. In addition, in myeloma cells the smooth ER subcompartment, containing endogenous retrovirus particles, was devoid of rab1p-labeling. These results indicate that the pre-Golgi (intermediate) compartment consists of different membrane domains and its morphology can vary considerably between different cell types. Further, they suggest that the recruitment of rab1p to membranes occurs predominantly in a post-ER location and that the protein functions in targeting/fusion events within the pre- and cis-Golgi membranes.
- Published
- 1995
18. Erratum: Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations
- Author
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Kirsi Alakurtti, Ekkehard Weber, Riitta Rinne, Gerit Theil, Gerrit-Jan de Haan, Dick Lindhout, Paula Salmikangas, Pekka Saukko, Ulla Lahtinen, and Anna-Elina Lehesjoki
- Subjects
Genetics ,Genetics (clinical) - Published
- 2005
19. Sporting Behavior of Special Groups in Finland
- Author
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Ulla Lahtinen
- Subjects
medicine.medical_specialty ,Visually impaired ,State of health ,medicine ,Normalization (sociology) ,Physical Therapy, Sports Therapy and Rehabilitation ,Psychiatry ,Psychology ,Disability pension ,human activities ,Developmental psychology - Abstract
The present aspirations for equality, normalization, and integration have given rise to increased demand for further development of sport for special groups. This is dependent upon an understanding of the existing sporting behavior. This article describes several Finnish studies of the sporting behavior of persons on disability pension, war veterans, those chronically ill or disabled, the mentally handicapped, and the visually impaired. Sporting behavior depends on one’s free time, interests, earlier practices, age, gender, and state of health. Poor health or a disability limits sporting activity, but it may also lead to more rehabilitative sport and exercise. The findings of the studies reveal features that need to be developed in sport for special groups.
- Published
- 1989
20. Involvement of caveolin-2 in caveolar biogenesis in MDCK cells
- Author
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Paul Verkade, Ulla Lahtinen, Kai Simons, Robert G. Parton, and Masanori Honsho
- Subjects
Caveolin 2 ,Biophysics ,Fluorescent Antibody Technique ,Biology ,Caveolae ,Biochemistry ,Caveolins ,03 medical and health sciences ,Dogs ,Caveolin-2 ,Caveolin-1 ,Structural Biology ,Caveolin ,Genetics ,Animals ,Electrophoresis, Gel, Two-Dimensional ,Molecular Biology ,030304 developmental biology ,Epithelial polarity ,0303 health sciences ,Vesicle ,030302 biochemistry & molecular biology ,Caveola ,Cell Biology ,Raft ,Apical membrane ,Cell biology ,Microscopy, Electron ,Caveolin 1 ,MDCK - Abstract
Caveolins have been identified as key components of caveolae, specialized cholesterol-enriched raft domains visible as small flask-shaped invaginations of the plasma membrane. In polarized MDCK cells caveolin-1 and -2 are found together on basolateral caveolae whereas the apical membrane, where only caveolin-1 is present, lacks caveolae. Expression of a caveolin mutant prevented the formation of the large caveolin-1/-2 hetero-oligomeric complexes, and led to intracellular retention of caveolin-2 and disappearance of caveolae from the basolateral membrane. Correspondingly, in MDCK cells over-expressing caveolin-2 the basolateral membrane exhibited an increased number of caveolae. These results indicate the involvement of caveolin-2 in caveolar biogenesis.
- Full Text
- View/download PDF
21. Metabolic profiling of serum and adipose tissue of monozygotic twins after high-fat meal
- Author
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Sirkku Jäntti, Maarit Kivilompolo, Ismo Mattila, Tuulikki Seppänen-Laakso, Heli Nygren, Anna-Liisa Ruskeepää, Ulla Lahtinen, Jaakko Kaprio, Jing Tang, Kirsi Pietiläinen, Tuulia Hyötyläinen, and Matej Oresic
22. Ultrahigh-performance liquid chromatography-mass spectrometry in lipidomics
- Author
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Tuulia Hyötyläinen, Ulla Lahtinen, Tuulikki Seppänen-Laakso, Matej Orešič, Päivi Pöhö, and Heli Nygren
- Abstract
An analytical method for the global profiling of molecular lipids in biological samples, with particular emphasis on the plasmalogen lipids, is described. The global profiling method is based on ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight-mass spectrometry (UHPLC–QTOF-MS). The profiling approach is complemented by UHPLC–LTQ-Orbitrap mass spectrometry in MS n mode for de novo lipid identification.
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