| 1. |
- Korkman, Marit, et al.
(författare)
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Neurocognitive test profiles of extremely low birth weight five-year-old children differ according to neuromotor status
- 2008
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Ingår i: Developmental Neuropsychology. - : Informa UK Limited. - 8756-5641 .- 1532-6942. ; 33:5, s. 637-655
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Tidskriftsartikel (refereegranskat)abstract
- The neurocognitive outcome of children born with extremely low birth weight (ELBW) is highly variable due to the complexity of morbidity. So far, no study has compared comprehensive neuropsychological test profiles in groups with different neuromotor status. In a national cohort of ELBW children neuropsychological test profiles were assessed in 4 groups defined according to a neurological examination at 5 years of age: normal neuromotor status (N = 56). motor coordination problems (N = 32), Multiple Subtle neuromotor signs including, both motor coordination problems and deviant reflexes (N = 20), and spastic diplegia (N = 12). The neurocognitive assessment included a test of intelligence. the Wechsler Primary and Preschool Scale of Intelligence-Revised (WPPSI-R) and 14 subtests of attention and executive functions, verbal functions, Manual motor functions, visuoconstructional functions and verbal learning (NEPSY). The children with normal neuromotor status performed within the average range: children with motor coordination problems had widespread impairment and children with spastic diplegia and children with multiple minor neuromotor(Or Signs had uneven test profiles with stronger verbal results but weaknesses in attention and executive functions, and in manual motor and visuoconstructional tasks. In conclusion, very preterm children with neuromotor signs, including motor coordination problems, are at risk for neurocognitive impairment. in spite of average intelligence. More impaired children have more irregular test profiles. Follow-up and neuropsychological assessment of very preterm children with minor neuromotor signs are therefore indicated.
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| 2. |
- Haataja, Daniel, et al.
(författare)
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Letters to the Paulaharjus from Ruija : the emergence of two writing cultures in Finnish among Kvens in the early twentieth century
- 2023
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Ingår i: Nordic Journal of Linguistics. - : Cambridge University Press. - 0332-5865 .- 1502-4717. ; 46:2, s. 215-251
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Tidskriftsartikel (refereegranskat)abstract
- Samuli Paulaharju was a Finnish ethnographer who visited the Kven minority in Northern Norway – Ruija – in the 1920s and 1930s. Together with his wife Jenny he collected ethnographic material among the Kvens, and corresponded frequently with some of them. Many wrote in Finnish, and most were self-taught writers.We focus on the orthography used by these writers who were writing in a multilingual environment. We identify two writing cultures, one associated with Old Literary Finnish and Early Modern Finnish, the other with Modern Written Finnish (MWF). The orthography used by the former is characterized by the use of b, d, g for p, t, k in native Finnish words, which we attribute to influence from Norwegian. By contrast, the orthography of the latter largely resembles the MWF of the time. However, both groups substitute t for d – a phenomenon found in Finland during the same time period – as well as occasionally use Norwegian characters.
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| 3. |
- Mojtaba Ghiasi, Seyed, et al.
(författare)
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The Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 is Essential for Proinsulin Handling
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:4, s. 747-760
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Tidskriftsartikel (refereegranskat)abstract
- Although endoplasmic reticulum (ER) chaperone binding to mutant proinsulin has been reported, the role of protein chaperones in the handling of wild-type proinsulin is under-investigated. Here, we have explored the importance of glucose regulated protein 94 (GRP94), a prominent ER chaperone known to fold insulin-like growth factors, in proinsulin handling within β-cells. We found that GRP94 co-immunoprecipitated with proinsulin and that inhibition of GRP94 function and/or expression reduced glucose-dependent insulin secretion, shortened proinsulin half-life and lowered intracellular proinsulin and insulin levels. This phenotype was accompanied by post-ER proinsulin misprocessing and higher numbers of enlarged insulin granules that contained amorphic material with reduced immunogold staining for mature insulin. Insulin granule exocytosis was two-fold accelerated but the secreted insulin had diminished bioactivity. Moreover, GRP94 knockdown or knockout in β-cells selectively activated Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK), without increasing apoptosis levels. Finally, GRP94 mRNA was overexpressed in islets from T2D patients. We conclude that GRP94 is a chaperone crucial for proinsulin handling and insulin secretion.
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| 4. |
- Plunkett, Jevon, et al.
(författare)
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An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened.8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.
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| 5. |
- Plunkett, Jevon, et al.
(författare)
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Mother's Genome or Maternally-Inherited Genes Acting in the Fetus Influence Gestational Age in Familial Preterm Birth
- 2009
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Ingår i: Human Heredity. - : S. Karger AG. - 1423-0062 .- 0001-5652. ; 68:3, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective: While multiple lines of evidence suggest the importance of genetic contributors to risk of preterm birth, the nature of the genetic component has not been identified. We perform segregation analyses to identify the best fitting genetic model for gestational age, a quantitative proxy for preterm birth. Methods: Because either mother or infant can be considered the proband from a preterm delivery and there is evidence to suggest that genetic factors in either one or both may influence the trait, we performed segregation analysis for gestational age either attributed to the infant (infant's gestational age), or the mother (by averaging the gestational ages at which her children were delivered), using 96 multiplex preterm families. Results: These data lend further support to a genetic component contributing to birth timing since sporadic (i.e. no familial resemblance) and nontransmission (i.e. environmental factors alone contribute to gestational age) models are strongly rejected. Analyses of gestational age attributed to the infant support a model in which mother's genome and/or maternally-inherited genes acting in the fetus are largely responsible for birth timing, with a smaller contribution from the paternally-inherited alleles in the fetal genome. Conclusion: Our findings suggest that genetic influences on birth timing are important and likely complex. Copyright (C) 2009 S. Karger AG, Basel
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| 6. |
- Plunkett, Jevon, et al.
(författare)
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Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth
- 2010
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods: We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results: Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions: Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
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| 7. |
- Taneera, Jalal, et al.
(författare)
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Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells
- 2018
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 472, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA1c. However, their impact on insulin secretion is still ambiguous. Here in, we investigated the role of FTO and ARL15 using GRINCH (Glucose-Responsive Insulin-secreting C-peptide-modified Human proinsulin) clonal rat β-cells. GRINCH cells have inserted GFP into the human C-peptide insulin gene. Hence, secreted CpepGFP served to monitor insulin secretion. mRNA silencing of FTO in GRINCH cells showed a significant reduction in glucose but not depolarization-stimulated insulin secretion, whereas ARL15 silencing had no effect. A significant down-regulation of insulin mRNA was observed in FTO knockdown cells. Type-2 Diabetic islets revealed a reduced expression of FTO mRNA. In conclusion, our data suggest that fluorescent CpepGFP released from GRINCH cells may serve as a convenient marker for insulin secretion. Silencing of FTO expression, but not ARL15, inhibits insulin secretion by affecting metabolic signaling.
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| 8. |
- Uusitalo, Karoliina, et al.
(författare)
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Hammersmith Infant Neurological Examination and long-term cognitive outcome in children born very preterm
- 2021
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Ingår i: Developmental Medicine & Child Neurology. - : John Wiley & Sons. - 0012-1622 .- 1469-8749. ; 63:8, s. 947-953
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the association between the Hammersmith Infant Neurological Examination (HINE) at age 2 years and neurocognition at age 11 years in children born very preterm. We hypothesized that the HINE at 2 years would be associated with neurocognition, that is, neurological, motor, and cognitive outcomes at 11 years.Method: A total of 174 children (mean gestational age 29.0wks, SD 2.7; minimum 23.0, maximum 35.9; 95 [55%] males, 79 [45%] females) born very preterm (birthweight <= 1500g/gestational age <32wks), were included in a prospective cohort recruited from 2001 to 2006 in Turku, Finland. The HINE was performed at 2 years' corrected age. Neurocognition at 11 years was assessed with the Touwen Infant Neurological Examination (TINE) , Movement Assessment Battery for Children, Second Edition (MABC-2), and full-scale IQ (Wechsler Intelligence Scale for Children, Fourth Edition).Results: The HINE global score was associated with the results of the TINE (odds ratio [OR]=0.9, 95% confidence interval [CI] 0.8-0.9, p=0.001), MABC-2 (beta=1.4, 95% CI 0.7-2.2, p<0.001), and full-scale IQ (beta=1.2, 95% CI 0.8-1.7, p<0.001), even when adjusted. When children with cerebral palsy (CP) were excluded, the HINE was still associated with full-scale IQ (unadjusted beta=1.2, 95% CI 0.3-2.1, p=0.01).Interpretation: A higher HINE global score at 2 years was associated with better general intelligence at 11 years even in children without CP. The HINE may be a useful tool to detect children at risk for later cognitive impairment.
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| 9. |
- Uusitalo, Karoliina, et al.
(författare)
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Preterm children's developmental coordination disorder, cognition and quality of life : a prospective cohort study
- 2020
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Ingår i: BMJ Paediatrics Open. - : BMJ. - 2399-9772. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate the rate of developmental coordination disorder (DCD) and its correlation to cognition and self-experienced health-related quality of life (HRQoL) in children born very preterm.DesignProspective follow-up study.SettingRegional population of children born very preterm in Turku University Hospital, Finland, in 2001-2006.PatientsA total of 170 children born very preterm were followed up until 11 years of age.Main outcome measuresMotor and cognitive outcomes were evaluated using the Movement Assessment Battery for Children - Second Edition (Movement ABC-2) and the Wechsler Intelligence Scale for Children - Fourth Edition, respectively, and HRQoL using the 17-Dimensional Illustrated Questionnaire (17D). The Touwen neurological examination was performed to exclude other neurological conditions affecting the motor outcome.ResultsEighteen children born very preterm (17 boys) (11.3%) had DCD, defined as Movement ABC-2 total test score <= 5th percentile. A positive correlation between motor and cognitive outcome (r=0.22, p=0.006) was found. Children born very preterm with DCD had lower cognitive scores than those without DCD (Full-Scale IQ mean 76.8 vs 91.6, p=0.001). Moreover, children born very preterm with DCD reported lower HRQoL than children born very preterm without motor impairment (17D mean 0.93 vs 0.96, p=0.03). However, HRQoL was higher in this group of children born very preterm compared with population-based normative test results (p<0.001).ConclusionsDCD was still common at 11 years of age in children born very preterm in 2000s. DCD associated with adverse cognitive development and lower self-experienced HRQoL. However, this group of children born very preterm reported better HRQoL in comparison with Finnish norms.
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