FLEXIQinase, a mass spectrometry-based assay, to unveil multikinase mechanisms.

We introduce a mass spectrometry-based method that provides residue-resolved quantitative information about protein phosphorylation. In this assay we combined our full-length expressed stable isotope-labeled protein for quantification strategy (FLEXIQuant) with a traditional kinase assay to determine the mechanisms of multikinase substrate phosphorylation such as priming-dependent kinase activities. The assay monitors the decrease in signal intensity of the substrate peptides and the concomitant increase in the (n × 80 Da)-shifted phosphorylated peptide.

Refractive Development in the "ROP Rat".

Although retinopathy of prematurity (ROP) is clinically characterized by abnormal retinal vessels at the posterior pole of the eye, it is also commonly characterized by vascular abnormalities in the anterior segment, visual dysfunction which is based in retinal dysfunction, and, most commonly of all, arrested eye growth and high refractive error, particularly (and paradoxically) myopia. The oxygen-induced retinopathy rat model of ROP presents neurovascular outcomes similar to the human disease, although it is not yet known if the "ROP rat" also models the small-eyed myopia characteristic of ROP. In this study, magnetic resonance images (MRIs) of albino (Sprague-Dawley) and pigmented (Long-Evans) ROP rat eyes, and age- and strain-matched room-air-reared (RAR) controls, were examined.

Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2.

Hereditary hemochomatosis (HH) is caused by mutations in several genes, including HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases expression of the iron regulatory hormone hepcidin by the liver, leading to inappropriately high iron uptake from the diet, and resulting in systemic iron overload. In tissue culture, overexpressed HFE and TFR2 physically interact.

Neuron deficit in the white matter and subplate in periventricular leukomalacia.

Objective: The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility is that damage to white matter and subplate neurons that are critical to the formation of the cerebral cortex occurs in conjunction with oligodendrocyte and axonal injury in PVL. We tested the hypothesis that the overall density of neurons in the white matter and subplate region is significantly lower in PVL cases compared to non-PVL controls.

PTEN hamartoma of soft tissue: a distinctive lesion in PTEN syndromes.

PTEN hamartoma tumor syndrome (PHTS) presents in a spectrum that encompasses the eponymous disorders Cowden and Bannayan-Riley-Ruvalcaba. Herein, we delineate the distinctive histopathology of a predominantly intramuscular lesion in PHTS, often called "arteriovenous malformation," because of certain imaging and histopathologic features. Cases were identified by review of lesions resected from patients with PHTS registered at our Vascular Anomalies Center and of unusual intramuscular vascular anomalies in our pathology database from 1985 to 2008.

Muenke syndrome associated with multiple osteochondromas.

Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies. Although this mutation is involved in bone growth and development, bony tumors are rare in this condition. We describe a patient with a molecular diagnosis of Muenke syndrome who also presented with multiple osteochondromas of the upper and lower extremities.

Hepatic mesenchymal hamartoma and infantile hemangioma: a rare association.

Background/purpose: The association between liver infantile hemangioma and mesenchymal hamartoma is rare. This communication reports the clinical, radiologic, and pathologic features of 3 infants with concurrent liver hemangioma and mesenchymal hamartoma.

Methods: We conducted a comprehensive search of the database of our Vascular Anomalies Center over the past 12 years (1999-2010) for the keywords mesenchymal hamartoma, liver, and hemangioma in a large cohort of patients with liver hemangioma.

Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma.

Medulloblastomas are the most common malignant brain tumors in children. Several large-scale genomic studies have detailed their heterogeneity, defining multiple subtypes with unique molecular profiles and clinical behavior. Increased expression of the miR-183~96~182 cluster of microRNAs has been noted in several subgroups, including the most clinically aggressive subgroup associated with genetic amplification of MYC.

iCanPlot: visual exploration of high-throughput omics data using interactive Canvas plotting.

Increasing use of high throughput genomic scale assays requires effective visualization and analysis techniques to facilitate data interpretation. Moreover, existing tools often require programming skills, which discourages bench scientists from examining their own data. We have created iCanPlot, a compelling platform for visual data exploration based on the latest technologies.

Four-year longitudinal performance of a population-based sample of healthy children on a neuropsychological battery: the NIH MRI study of normal brain development.

The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. Cross-sectional findings from the neuropsychological test battery have been previously described (Waber et al., 2007).

Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity.

For prevention of Streptococcus pneumoniae (pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens.

NIDCAP improves brain function and structure in preterm infants with severe intrauterine growth restriction.

Objective: The effect of NIDCAP (Newborn Individualized Developmental Care and Assessment Program) was examined on the neurobehavioral, electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction (IUGR).

Study Design: A total of 30 infants, 27-33 weeks gestation, were randomized to control (C; N=17) or NIDCAP/experimental (E; N=13) care. Baseline health and demographics were assessed at intake; electroencephalography (EEG) and magnetic resonance imaging (MRI) at 35 and 42 weeks postmenstrual age; and health, growth and neurobehavior at 42 weeks and 9 months corrected age (9 months).

A system for coreference resolution for the clinical narrative.

Objective: To research computational methods for coreference resolution in the clinical narrative and build a system implementing the best methods.

Methods: The Ontology Development and Information Extraction corpus annotated for coreference relations consists of 7214 coreferential markables, forming 5992 pairs and 1304 chains. We trained classifiers with semantic, syntactic, and surface features pruned by feature selection.

Fourth-dimensional changes in nasolabial dimensions following rotation-advancement repair of unilateral cleft lip.

Background: Repair of unilateral cleft lip requires three-dimensional craftsmanship and understanding four-dimensional changes.

Methods: Ninety-nine children with unilateral complete or incomplete cleft lip were measured by direct anthropometry following rotation-advancement repair (intraoperatively) and again in childhood. Changes in heminasal width, labial height, and labial width were analyzed and compared measures depending on whether the cleft was incomplete/complete or involved left/right side.

Current pharmacologic approaches for prevention and treatment of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth and has serious adverse long-term health consequences. The etiology of BPD is complex, multifactorial, and incompletely understood. Contributing factors include ventilator-induced lung injury, exposure to toxic oxygen levels, and infection.

Multiscale information for network characterization in epilepsy.

We have developed a multiscale approach for the estimation of neuronal network coordination in the epileptic brain, from continuous (long-term) non-invasive electroencephalograms (EEG). The proposed approach specifically assesses the effect of large-scale network behavior on local network coordination, at individual dominant frequencies (modes) of the EEG spectrum. For this purpose a set of conditional information parameters is proposed to explicitly quantify the effect of global network correlation in the brain on pairwise (local) mutual information, via conditioning.

Estimation of correlations between copy-number variants in non-coding DNA.

Allelic DNA aberrations across our genome have been associated with normal human genetic heterogeneity as well as with a number of diseases and disorders. When copy-number variations (CNVs) occur in gene-coding regions, known relationships between genes may help us understand correlations between CNVs. However, a large number of these aberrations occur in non-coding, extragenic regions and their correlations may be characterized only quantitatively, e.

Novel zebrafish model reveals a critical role for MAPK in lymphangiogenesis.

Purpose: Lymphatic disorders are poorly understood with few animal models. We designed a novel assay to measure lymphatic development using transgenic zebrafish with fluorescently labeled endothelial cells. Two major branches of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were examined: the MAPK and PI3K pathways.

Outcomes in pediatric atypical spitz tumors treated without sentinel lymph node biopsy.

The diagnosis of atypical Spitz tumor (AST) in a pediatric patient conveys an uncertain potential for malignancy. Although pediatric melanoma is rare, AST may be treated aggressively with sentinel lymph node biopsy (SLNB) and subsequent completion lymphadenectomy. These procedures have unclear therapeutic benefit and potential morbidity.

The clinical presentation and surgical management of adnexal torsion in the pediatric and adolescent population.

Study Objective: To determine the history, clinical presentation, physical exam, and laboratory findings of ovarian and/or tubal torsion in the pediatric and adolescent population and to examine the surgical management of adnexal torsion.

Design: Descriptive, retrospective chart review.

Setting: Academic children's hospital.

Paxillin mediates sensing of physical cues and regulates directional cell motility by controlling lamellipodia positioning.

Physical interactions between cells and the extracellular matrix (ECM) guide directional migration by spatially controlling where cells form focal adhesions (FAs), which in turn regulate the extension of motile processes. Here we show that physical control of directional migration requires the FA scaffold protein paxillin. Using single-cell sized ECM islands to constrain cell shape, we found that fibroblasts cultured on square islands preferentially activated Rac and extended lamellipodia from corner, rather than side regions after 30 min stimulation with PDGF, but that cells lacking paxillin failed to restrict Rac activity to corners and formed small lamellipodia along their entire peripheries.

Developmental regulation of group I metabotropic glutamate receptors in the premature brain and their protective role in a rodent model of periventricular leukomalacia.

Cerebral white matter injury in premature infants, known as periventricular leukomalacia (PVL), is common after hypoxia-ischemia (HI). While ionotropic glutamate receptors (iGluRs) can mediate immature white matter injury, we have previously shown that excitotoxic injury to premyelinating oligodendrocytes (preOLs) in vitro can be attenuated by group I metabotropic glutamate receptor (mGluR) agonists. Thus, we evaluated mGluR expression in developing white matter in rat and human brain, and tested the protective efficacy of a central nervous system (CNS)-penetrating mGluR agonist on injury to developing oligodendrocytes (OLs) in vivo.