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Author Leena Haataja

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Distinct states of proinsulin misfolding in MIDY.

Leena Haataja, Anoop Arunagiri, Anis Hassan, Kaitlin Regan, Billy Tsai, Balamurugan Dhayalan, Michael A Weiss, Ming Liu, Peter Arvan,

A precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) "interchain" disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. The third proinsulin disulfide, Cys(A6)-Cys(A11), is not required for anterograde trafficking, i.e., a "lose-A6/A11" mutant [Cys(A6), ... Read more >>

Cell Mol Life Sci (Cellular and molecular life sciences : CMLS)
[2021, :]

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Neurocognitive and Motor Functions in Biliary Atresia Patients: A Cross-Sectional, Prospective National Cohort Study.

Satu Ruuska, Mikko Lähteenmäki, Taru Häyrinen, Kaisa Kanerva, Timo Jahnukainen, Leena Haataja, Kaija-Leena Kolho, Mikko P Pakarinen,

<h4>Objectives</h4>To evaluate the neurocognitive and motor development of biliary atresia (BA) patients in childhood and adolescence and to identify risk factors for impaired outcome.<h4>Methods</h4>We invited all BA patients between ages 1-20 years followed up at Helsinki University Children's Hospital in Finland between 1 January 2019 to 31 January 2020 to participate. ... Read more >>

J Pediatr Gastroenterol Nutr (Journal of pediatric gastroenterology and nutrition)
[2021, :]

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Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes

Maroof Alam, Anoop Arunagiri, Leena Haataja, Mauricio Torres, Dennis Larkin, John Kappler, Niyun Jin, Peter Arvan,

Throughout evolution, proinsulin has exhibited significant sequence variation in both C-peptide and insulin moieties. As the proinsulin coding sequence evolves, the gene product continues to be under selection pressure both for ultimate insulin bioactivity and for the ability of proinsulin to be folded for export through the secretory pathway of ... Read more >>

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Adaptation to chronic ER stress enforces pancreatic β-cell plasticity

Chien-Wen Chen, Bo-Jhih Guan, Mohammed Alzahrani, Zhaofeng Gao, Long Gao, Syrena Bracey, Leena Haataja, Ashleigh Schaffer, Hugo Lee, Thomas Laframboise, Ilya Bederman, Peter Arvan, Clayton Mathews, Ivan Gerling, Klaus Kaestner, Boaz Tirosh, Feyza Engin, Maria Hatzoglou,

Pancreatic β-cells undergo high levels of endoplasmic reticulum (ER) stress due to their role in insulin secretion. Hence, they require sustainable and efficient adaptive stress responses to cope with the stress. Whether duration and episodes of chronic ER stress directly compromises β-cell identity is largely unknown. We show that under ... Read more >>

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Distinct states of proinsulin misfolding in MIDY

Leena Haataja, Anoop Arunagiri, Anis Hassan, Kaitlin Regan, Billy Tsai, Balamurugan Dhayalan, Michael Weiss, Ming Liu, Peter Arvan,

A precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) “interchain” disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. The third proinsulin disulfide, Cys(A6)-Cys(A11), is not required for anterograde trafficking, i.e., a “lose-A6/A11” mutant [Cys(A6), ... Read more >>

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Hammersmith Infant Neurological Examination and long-term cognitive outcome in children born very preterm.

Karoliina Uusitalo, Leena Haataja, Anna Nyman, Tuomo Lehtonen, Sirkku Setänen, ,

<h4>Aim</h4>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.<h4>Method</h4>A total of 174 children (mean ... Read more >>

Dev Med Child Neurol (Developmental medicine and child neurology)
[2021, 63(8):947-953]

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Altered β-Cell Prohormone Processing and Secretion in Type 1 Diabetes.

Teresa Rodriguez-Calvo, Yi-Chun Chen, C Bruce Verchere, Leena Haataja, Peter Arvan, Pia Leete, Sarah J Richardson, Noel G Morgan, Wei-Jun Qian, Alberto Pugliese, Mark Atkinson, Carmella Evans-Molina, Emily K Sims,

Analysis of data from clinical cohorts, and more recently from human pancreatic tissue, indicates that reduced prohormone processing is an early and persistent finding in type 1 diabetes. In this article, we review the current state of knowledge regarding alterations in islet prohormone expression and processing in type 1 diabetes ... Read more >>

Diabetes (Diabetes)
[2021, 70(5):1038-1050]

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The impact of susceptibility correction on diffusion metrics in adolescents.

Katri Lahti, Riitta Parkkola, Päivi Jääsaari, Leena Haataja, Virva Saunavaara, ,

<h4>Background</h4>Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values.<h4>Objective</h4>To explore the impact of susceptibility correction on diffusion metrics.<h4>Materials and methods</h4>A cohort of 27 healthy adolescents (18 boys, 9 girls, mean age ... Read more >>

Pediatr Radiol (Pediatric radiology)
[2021, 51(8):1471-1480]

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Reduced replication fork speed promotes pancreatic endocrine differentiation and controls graft size.

Lina Sui, Yurong Xin, Qian Du, Daniela Georgieva, Giacomo Diedenhofen, Leena Haataja, Qi Su, Michael V Zuccaro, Jinrang Kim, Jiayu Fu, Yuan Xing, Yi He, Danielle Baum, Robin S Goland, Yong Wang, Jose Oberholzer, Fabrizio Barbetti, Peter Arvan, Sandra Kleiner, Dieter Egli,

Limitations in cell proliferation are important for normal function of differentiated tissues and essential for the safety of cell replacement products made from pluripotent stem cells, which have unlimited proliferative potential. To evaluate whether these limitations can be established pharmacologically, we exposed pancreatic progenitors differentiating from human pluripotent stem cells ... Read more >>

JCI Insight (JCI insight)
[2021, 6(5):]

Cited: 2 times

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Social functioning questionnaires of adolescents born preterm show average profiles and attenuated sex differences.

Susanna Salomäki, Päivi Rautava, Niina Junttila, Mira Huhtala, Marika H Leppänen, Anna Nyman, Mari Koivisto, Leena Haataja, Liisa Lehtonen, Riikka Korja, ,

<h4>Aim</h4>Prematurity has been shown to affect social competence in children and adults. Our aim was to evaluate profiles of self-reported social behaviours and loneliness in preterm- and term-born adolescents.<h4>Methods</h4>Preterm (≤1500 g and, or, <32 gestational weeks)- and term-born infants were recruited in Turku University Hospital from 2001 to 2006. The Multisource ... Read more >>

Acta Paediatr (Acta paediatrica (Oslo, Norway : 1992))
[2021, 110(5):1490-1497]

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Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.

Ming Liu, Yumeng Huang, Xiaoxi Xu, Xin Li, Maroof Alam, Anoop Arunagiri, Leena Haataja, Li Ding, Shusen Wang, Pamela Itkin-Ansari, Randal J Kaufman, Billy Tsai, Ling Qi, Peter Arvan,

Both basal and glucose-stimulated insulin release occur primarily by insulin secretory granule exocytosis from pancreatic β cells, and both are needed to maintain normoglycemia. Loss of insulin-secreting β cells, accompanied by abnormal glucose tolerance, may involve simple exhaustion of insulin reserves (which, by immunostaining, appears as a loss of β ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2021, 131(2):]

Cited: 1 time

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Hammersmith Infant Neurological Examination for infants born preterm: predicting outcomes other than cerebral palsy.

Domenico M Romeo, Frances M Cowan, Leena Haataja, Daniela Ricci, Elisa Pede, Francesca Gallini, Francesco Cota, Claudia Brogna, Giovanni Vento, Mario G Romeo, Eugenio Mercuri,

<h4>Aim</h4>We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP).<h4>Method</h4>We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months ... Read more >>

Dev Med Child Neurol (Developmental medicine and child neurology)
[2021, 63(8):939-946]

Cited: 2 times

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The training and organization of Paediatric Neurology in Europe: Special report of the European Paediatric Neurology Society & Committee of National Advisors.

Dana Craiu, Leena Haataja, Katalin Hollody, Pavel Kršek, Lieven Lagae, Volker Mall, Alasdair Pj Parker, Maja Steinlin, Dilek Yalnizoglu, Coriene Catsman-Berrevoets, ,

<h4>Background</h4>Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management and research into diseases of the central and peripheral nervous system from fetal life to transition into adulthood. The European Paediatric Neurology Society first designed and published the European PN training programme in the European Paediatric Neurology Syllabus in ... Read more >>

Eur J Paediatr Neurol (European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society)
[2020, 28:6-15]

Cited: 1 time

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Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

Annika Lind, Leena Haataja, Marja Laasonen, Virva Saunavaara, Henry Railo, Tuomo Lehtonen, Victor Vorobyev, Karoliina Uusitalo, Katri Lahti, Riitta Parkkola, ,

<h4>Objectives</h4>Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better ... Read more >>

J Int Neuropsychol Soc (Journal of the International Neuropsychological Society : JINS)
[2021, 27(3):270-281]

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Abnormalities in proinsulin processing in islets from individuals with longstanding T1D.

Emily K Sims, Farooq Syed, Julius Nyalwidhe, Henry T Bahnson, Leena Haataja, Cate Speake, Margaret A Morris, Appakalai N Balamurugan, Raghavendra G Mirmira, Jerry Nadler, Teresa L Mastracci, Peter Arvan, Carla J Greenbaum, Carmella Evans-Molina,

We recently described the persistence of detectable serum proinsulin in a large majority of individuals with longstanding type 1 diabetes (T1D), including individuals with undetectable serum C-peptide. Here, we sought to further explore the mechanistic etiologies of persistent proinsulin secretion in T1D at the level of the islet, using tissues ... Read more >>

Transl Res (Translational research : the journal of laboratory and clinical medicine)
[2019, 213:90-99]

Cited: 11 times

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Biological behaviors of mutant proinsulin contribute to the phenotypic spectrum of diabetes associated with insulin gene mutations.

Heting Wang, Cécile Saint-Martin, Jialu Xu, Li Ding, Ruodan Wang, Wenli Feng, Ming Liu, Hua Shu, Zhenqian Fan, Leena Haataja, Peter Arvan, Christine Bellanné-Chantelot, Jingqiu Cui, Yumeng Huang,

Insulin gene mutation is the second most common cause of neonatal diabetes (NDM). It is also one of the genes involved in maturity-onset diabetes of the young (MODY). We aim to investigate molecular behaviors of different INS gene variants that may correlate with the clinical spectrum of diabetes phenotypes. In ... Read more >>

Mol Cell Endocrinol (Molecular and cellular endocrinology)
[2020, 518:111025]

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Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age.

Hanna Kallankari, Virva Saunavaara, Riitta Parkkola, Leena Haataja, Mikko Hallman, Tuula Kaukola,

<h4>Background</h4>Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later.<h4>Objective</h4>The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal ... Read more >>

Pediatr Radiol (Pediatric radiology)
[2021, 51(1):112-118]

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Brain volumes in relation to loneliness and social competence in preadolescents born very preterm.

Annika Lind, Susanna Salomäki, Riitta Parkkola, Leena Haataja, Päivi Rautava, Niina Junttila, Juha Koikkalainen, Jyrki Lötjönen, Virva Saunavaara, Riikka Korja, ,

<h4>Introduction</h4>The aim of the present study was to assess how regional brain volumes associate with self-experienced social and emotional loneliness and social competence in very preterm and term-born preadolescents.<h4>Materials and methods</h4>Thirty-four very preterm subjects (birthweight ≤1,500 g and/or gestational age <32 weeks) without neurodevelopmental impairments and/or major brain pathologies and 31 term-born ... Read more >>

Brain Behav (Brain and behavior)
[2020, 10(6):e01640]

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The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis

Gaelle Carrat, Elizabeth Haythorne, Alejandra Tomas, Leena Haataja, Andreas Müller, Peter Arvan, Alexandra Piunti, Kaiying Cheng, Mutian Huang, Timothy Pullen, Eleni Georgiadou, Theodoros Stylianides, Nur Shabrina Amirruddin, Victoria Salem, Walter Distaso, Andrew Cakebread, Kate Heesom, Philip Lewis, David Hodson, Linford Briant, Annie C.H. Fung, Richard Sessions, Fabien Alpy, Alice P.S. Kong, Peter Benke, Federico Torta, Adrian Kee Keong Teo, Isabelle Leclerc, Michele Solimena, Dale Wigley, Guy Rutter,

<h4>Objective</h4> Risk alleles for type 2 diabetes at the STARD10 locus are associated with lowered STARD10 expression in the β-cell, impaired glucose-induced insulin secretion and decreased circulating proinsulin:insulin ratios. Although likely to serve as a mediator of intracellular lipid transfer, the identity of the transported lipids, and thus the pathways ... Read more >>

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Visual Perceptual Skills in Very Preterm Children: Developmental Course and Associations With Neural Activation.

Annika Lind, Riitta Parkkola, Marja Laasonen, Victor Vorobyev, Leena Haataja, ,

<h4>Background</h4>The objective of this study was to examine how nonverbal skills at age five years relate to visual perception and brain activation during visual perception tasks at age 12 years in very preterm subjects without visual or other neurodevelopmental impairments or major brain pathologies.<h4>Methods</h4>At age five years, 36 prematurely born ... Read more >>

Pediatr Neurol (Pediatric neurology)
[2020, 109:72-78]

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What Makes Participation Meaningful? Using Photo-Elicitation to Interview Children with Disabilities.

Nea Vänskä, Salla Sipari, Leena Haataja,

<h4>Aims</h4>The purpose of this study was to describe meaningful participation in everyday life from the perspectives of children with disabilities.<h4>Methods</h4>Nine children (5-10 years, mean age 7.2 years, 5 boys, 4 girls) with disabilities participated in individual photo-elicitation interviews. The interview data was transcribed verbatim and analyzed with inductive content analysis.<h4>Results</h4>The children's meaningful ... Read more >>

Phys Occup Ther Pediatr (Physical & occupational therapy in pediatrics)
[2020, 40(6):595-609]

Cited: 1 time

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Preterm children's developmental coordination disorder, cognition and quality of life: a prospective cohort study.

Karoliina Uusitalo, Leena Haataja, Anna Nyman, Liisi Ripatti, Mira Huhtala, Päivi Rautava, Liisa Lehtonen, Riitta Parkkola, Katri Lahti, Mari Koivisto, Sirkku Setänen,

<h4>Objective</h4>To 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.<h4>Design</h4>Prospective follow-up study.<h4>Setting</h4>Regional population of children born very preterm in Turku University Hospital, Finland, in 2001-2006.<h4>Patients</h4>A total of 170 children born very preterm were followed ... Read more >>

BMJ Paediatr Open (BMJ paediatrics open)
[2020, 4(1):e000633]

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Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells

Lina Sui, Yurong Xin, Daniela Georgieva, Giacomo Diedenhofen, Leena Haataja, Qi Su, Yong Wang, Michael Zuccaro, Jinrang Kim, Jiayu Fu, Yuan Xing, Danielle Baum, Robin Goland, Jose Oberholzer, Fabrizio Barbetti, Peter Arvan, Sandra Kleiner, Dieter Egli,

Limitations in cell proliferation are a key barrier to reprogramming differentiated cells to pluripotent stem cells, and conversely, acquiring these limitations may be important to establish the differentiated state. The pancreas, and beta cells in particular have a low proliferative potential, which limits regeneration, but how these limitations are established ... Read more >>

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Neonatal Intestinal Failure Is Independently Associated With Impaired Cognitive Development Later in Childhood.

Riikka J Gunnar, Kaisa Kanerva, Silja Salmi, Taru Häyrinen, Leena Haataja, Mikko P Pakarinen, Laura Merras-Salmio,

<h4>Objective</h4>The impact of pediatric intestinal failure (IF) on neurodevelopment beyond infancy has not been systematically studied. Our aim was to evaluate cognitive and motor impairment and to identify risk factors for adverse outcomes among children with IF.<h4>Methods</h4>We conducted a cross-sectional single-center study at the Helsinki University Children's Hospital. Patients with ... Read more >>

J Pediatr Gastroenterol Nutr (Journal of pediatric gastroenterology and nutrition)
[2020, 70(1):64-71]

Cited: 2 times

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Automatic Posture and Movement Tracking of Infants with Wearable Movement Sensors.

Manu Airaksinen, Okko Räsänen, Elina Ilén, Taru Häyrinen, Anna Kivi, Viviana Marchi, Anastasia Gallen, Sonja Blom, Anni Varhe, Nico Kaartinen, Leena Haataja, Sampsa Vanhatalo,

Infants' spontaneous and voluntary movements mirror developmental integrity of brain networks since they require coordinated activation of multiple sites in the central nervous system. Accordingly, early detection of infants with atypical motor development holds promise for recognizing those infants who are at risk for a wide range of neurodevelopmental disorders ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):169]

Cited: 7 times

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