Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes.

Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.

FOXG1 dose tunes cell proliferation dynamics in human forebrain progenitor cells.

Heterozygous loss-of-function mutations in Forkhead box G1 (FOXG1), a uniquely brain-expressed gene, cause microcephaly, seizures, and severe intellectual disability, whereas increased FOXG1 expression is frequently observed in glioblastoma. To investigate the role of FOXG1 in forebrain cell proliferation, we modeled FOXG1 syndrome using cells from three clinically diagnosed cases with two sex-matched healthy parents and one unrelated sex-matched control. Cells with heterozygous FOXG1 loss showed significant reduction in cell proliferation, increased ratio of cells in G0/G1 stage of the cell cycle, and increased frequency of primary cilia.

Regenerating Damaged Myocardium: A Review of Stem-Cell Therapies for Heart Failure.

Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. The death of cardiac myocyte is a fundamental pathological process in cardiac pathologies caused by various heart diseases, including myocardial infarction. Thus, strategies for replacing fibrotic tissue in the infarcted region with functional myocardium have long been a goal of cardiovascular research.

Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells.

Mutations in HPRT1, a gene encoding a rate-limiting enzyme for purine salvage, cause Lesch-Nyhan disease which is characterized by self-injury and motor impairments. We leveraged stem cell and genetic engineering technologies to model the disease in isogenic and patient-derived forebrain and midbrain cell types. Dopaminergic progenitor cells deficient in HPRT showed decreased intensity of all developmental cell-fate markers measured.

Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells.

Making high-quality dopamine (DA)-producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal-to-noise ratio due to low levels of cellular DA and the rate-limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L-type calcium agonist can significantly increase TH protein levels and DA content and release.

Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons.

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.

Differentiation of Human Induced Pluripotent Stem Cells (iPSCs) into an Effective Model of Forebrain Neural Progenitor Cells and Mature Neurons.

Induced Pluripotent Stem Cells (iPSCs) are pluripotent stem cells that can be generated from somatic cells, and provide a way to model the development of neural tissues . One particularly interesting application of iPSCs is the development of neurons analogous to those found in the human forebrain. Forebrain neurons play a central role in cognition and sensory processing, and deficits in forebrain neuronal activity contributes to a host of conditions, including epilepsy, Alzheimer's disease, and schizophrenia.

Disruption of GRIN2B Impairs Differentiation in Human Neurons.

Heterozygous loss-of-function mutations in GRIN2B, a subunit of the NMDA receptor, cause intellectual disability and language impairment. We developed clonal models of GRIN2B deletion and loss-of-function mutations in a region coding for the glutamate binding domain in human cells and generated neurons from a patient harboring a missense mutation in the same domain. Transcriptome analysis revealed extensive increases in genes associated with cell proliferation and decreases in genes associated with neuron differentiation, a result supported by extensive protein analyses.

Starch-derived absorbable polysaccharide hemostat enhances bone healing via BMP-2 protein.

Surgical hemostasis is critical in reducing the likelihood of excessive bleeding and blood transfusion. In treating some cases, commonly used hemostatic agent showed limited efficacy and prolonged degradation and clearance, causing an inhibition of bone healing. Starch absorbable polysaccharide (SAPH) is a novel hemostatic agent made from a plant starch, which can be completely absorbed and achieve better hemostatic effects than many commonly used hemostatic agents.

Prevalence and factors of addictive Internet use among adolescents in Wuhan, China: interactions of parental relationship with age and hyperactivity-impulsivity.

Purposes: This study examined the prevalence of addictive Internet use and analyzed the role of parental relationship in affecting this behavior among a random sample of adolescents in Wuhan, China.

Methods: Students (n = 1,101) were randomly selected from four schools, including 638 boys and 463 girls with a mean age of 13.8 (standard deviation = 1.

Working-memory training improves developmental dyslexia in Chinese children.

Although plasticity in the neural system underlies working memory, and working memory can be improved by training, there is thus far no evidence that children with developmental dyslexia can benefit from working-memory training. In the present study, thirty dyslexic children aged 8-11 years were recruited from an elementary school in Wuhan, China. They received working-memory training, including training in visuospatial memory, verbal memory, and central executive tasks.

Proteomic profiles of soluble proteins from the esophageal gland in female Meloidogyne incognita.

Meloidogyne incognita can infect multiple plant species. Proteins synthesized in the esophageal glands and secreted through the stylet of plant parasitic nematodes play critical roles in the plant-nematode interactions. Female M.

A near-infrared brain function study of Chinese dyslexic children.

Recently, two findings using functional magnetic resonance imaging of dyslexic in Chinese show the left middle frontal gyrus is a crucial area associated with reading disability. The purpose of present study was to replicate the previous findings using near-infrared spectroscopy and a consonant-vowel task which engaged finer-grained phonological processing. Compared to the control group, our study showed the dyslexic children had decreased amounts of oxy-hemoglobin and total-hemoglobin in the left dorsolateral prefrontal cortex.

Association of polymorphisms in the DCDC2 gene with developmental dyslexia in the Han Chinese.

Background: Genetic association studies on populations of European origin have identified the DCDC2 gene as a susceptibility locus for developmental dyslexia. Here, we sought to investigate the association of DCDC2 polymorphisms with developmental dyslexia in children of Han Chinese origin.

Methods: We undertook a case-control genetic association study on 76 dyslexic children and 79 non-dyslexic matched controls.

Working memory function in Chinese dyslexic children: a near-infrared spectroscopy study.

The deficiency theories of dyslexia are quite contradictory and the cross-cultural studies in recent years mainly focused on whether the dyslexics among cultures shared the same cognitive profile or just based on the language. This study used Near-Infrared Spectroscopy (NIRS) imaging to measure the regional cerebral blood volume (BV) and the changes of cerebral activation in the left prefrontal cortex of 12 Chinese dyslexic children and their 12 age-matched normal controls during the Paced Visual Serial Addition Test (PVSAT). Results showed that the scores of PVSAT of dyslexic children were significantly lower than those of the normal children (t=3.

Inhibitory ability of children with developmental dyscalculia.

Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects.

[A pilot study of ocular diseases screening for neonates in China].

Objective: To explore the clinical strategies for the screening of newborn eye diseases and obtain information concerning the incidence of newborn ocular diseases.

Methods: Newborns in a baby-friendly nursery were evaluated for mass screening of eye diseases 2 to 7 days after birth (including reaction to light stimulation, external ocular examination and test for pupil red reflex) and those with abnormalities were subjected to diagnostic examination (external ocular examination with a hand-held slit-lamp, pupil red reflex and mydriatic examination). Newborns in neonatal intensive care unit (NICU) were subjected to screening 5 to 14 days after birth and then, together with those with high risk factors, received a comprehensive examination for screening and diagnostic purposes.

[Simultaneous screening program for newborns hearing and ocular diseases].

Objective: To explore the model and the feasibility of newborn hearing and ocular disease simultaneous screening program and to study the birth prevalence of newborn hearing loss and newborn ocular diseases.

Methods: The universal newborn hearing screening (UNHS) was performed using transient otoacoustic emission (TEOAE) in well baby nursery and by a two-stage TEOAE and auto auditory brainstem response (AABR) protocol in neonatal intensive care unit (NICU). The UNHS was simultaneous done with newborn ocular disease screening program.

A case-control study on high-risk factors for newborn hearing loss in seven cities of Shandong province.

To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis.

Neuron-specific Enolase and myelin basic protein in cerebrospinal fluid of patients with first episode schizophrenia.

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P<0.01).

Study on self-consciousness of children with learning disabilities and related factors.

Objective: To study the self-consciousness of children with learning disabilities (LD) and to identify related factors.

Methods: Five hundred and sixty pupils graded from 1 to 6 in an elementary school were investigated. According to the pupil rating scale revised screening for learning disabilities (PRS), combined Raven's test (CRT) and achievement of main courses, 35 of 560 pupils were diagnosed as LD children.

A bibliometric analysis of research on the behavior therapy in China and its trend.

To get formed of the status of research and application of the domestic behavior therapy and its development trend, the time distribution and the subject distribution were bibliometrically analyzed of the literature on behavior therapy from 1981 to 2000 in the CBMdisc. Our results showed that the number of literature of behavior therapy has been increasing in exponential manner over the past 20 years; the behavior modification, the biofeedback and the cognitive therapy are extensively used in China. In clinical practice, the behavior modification and the biofeedback have been applied in all departments of medical institutions, especially for treating the cardiovascular and the neurological conditions.

Risk factors of learning disabilities in Chinese children in Wuhan.

Objective: To investigate prevalence rate of learning disabilities (LD) in Chinese children, and to explore related risk factors, and to provide theoretical basis for preventing such disabilities.

Methods: One thousand and one hundred fifty one children were randomly selected in primary schools. According to criteria set by ICD-10, 118 children diagnosed as LD were classified into the study group.