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1.  The Tinkerbell (Tink) Mutation Identifies the Dual-Specificity MAPK Phosphatase INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5) as a Novel Regulator of Organ Size in Arabidopsis 
PLoS ONE  2015;10(7):e0131103.
Mitogen-activated dual-specificity MAPK phosphatases are important negative regulators in the MAPK signalling pathways responsible for many essential processes in plants. In a screen for mutants with reduced organ size we have identified a mutation in the active site of the dual-specificity MAPK phosphatase INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5) that we named tinkerbell (tink) due to its small size. Analysis of the tink mutant indicates that IBR5 acts as a novel regulator of organ size that changes the rate of growth in petals and leaves. Organ size and shape regulation by IBR5 acts independently of the KLU growth-regulatory pathway. Microarray analysis of tink/ibr5-6 mutants identified a likely role for this phosphatase in male gametophyte development. We show that IBR5 may influence the size and shape of petals through auxin and TCP growth regulatory pathways.
PMCID: PMC4492785  PMID: 26147117
2.  Real-Time 3D Magnetic Resonance Imaging of the Pharyngeal Airway in Sleep Apnea 
To investigate the feasibility of real-time 3D magnetic resonance imaging (MRI) with simultaneous recording of physiological signals for identifying sites of airway obstruction during natural sleep in pediatric patients with sleep-disordered breathing.
Experiments were performed using a three-dimensional Fourier transformation (3DFT) gradient echo sequence with prospective undersampling based on golden-angle radial spokes, and L1-norm regularized iterative self-consistent parallel imaging (L1-SPIRiT) reconstruction. This technique was demonstrated in three healthy adult volunteers and five pediatric patients with sleep-disordered breathing. External airway occlusion was used to induce partial collapse of the upper airway on inspiration and test the effectiveness of the proposed imaging method. Apneic events were identified using information available from synchronized recording of mask pressure and respiratory effort.
Acceptable image quality was obtained in seven of eight subjects. Temporary airway collapse induced via inspiratory loading was successfully imaged in all three volunteers, with average airway volume reductions of 63.3%, 52.5%, and 33.7%. Central apneic events and associated airway narrowing/closure were identified in two pediatric patients. During central apneic events, airway obstruction was observed in the retropalatal region in one pediatric patient.
Real-time 3D MRI of the pharyngeal airway with synchronized recording of physiological signals is feasible and may provide valuable information about the sites and nature of airway narrowing/collapse during natural sleep.
PMCID: PMC4159137  PMID: 23788203
MRI; upper airway; airway obstruction; sleep apnea; parallel imaging; constrained reconstruction
3.  Functional screening of willow alleles in Arabidopsis combined with QTL mapping in willow (Salix) identifies SxMAX4 as a coppicing response gene 
Plant Biotechnology Journal  2014;12(4):480-491.
Willows (Salix spp.) are important biomass crops due to their ability to grow rapidly with low fertilizer inputs and ease of cultivation in short-rotation coppice cycles. They are relatively undomesticated and highly diverse, but functional testing to identify useful allelic variation is time-consuming in trees and transformation is not yet possible in willow. Arabidopsis is heralded as a model plant from which knowledge can be transferred to advance the improvement of less tractable species. Here, knowledge and methodologies from Arabidopsis were successfully used to identify a gene influencing stem number in coppiced willows, a complex trait of key biological and industrial relevance. The strigolactone-related More AXillary growth (MAX) genes were considered candidates due to their role in shoot branching. We previously demonstrated that willow and Arabidopsis show similar response to strigolactone and that transformation rescue of Arabidopsis max mutants with willow genes could be used to detect allelic differences. Here, this approach was used to screen 45 SxMAX1, SxMAX2, SxMAX3 and SxMAX4 alleles cloned from 15 parents of 11 mapping populations varying in shoot-branching traits. Single-nucleotide polymorphism (SNP) frequencies were locus dependent, ranging from 29.2 to 74.3 polymorphic sites per kb. SxMAX alleles were 98%–99% conserved at the amino acid level, but different protein products varying in their ability to rescue Arabidopsis max mutants were identified. One poor rescuing allele, SxMAX4D, segregated in a willow mapping population where its presence was associated with increased shoot resprouting after coppicing and colocated with a QTL for this trait.
PMCID: PMC4238783  PMID: 24393130
Arabidopsis; allelic diversity; mutant rescue; Salix; QTL; strigolactone
4.  Hospital Readmissions for Newly Discharged Pediatric Home Mechanical Ventilation Patients 
Pediatric pulmonology  2011;47(4):409-414.
Ventilator-dependent children have complex chronic conditions that put them at risk for acute illness and repeated hospitalizations.
To determine the 12-month incidence of and risk factors for non-elective readmission in children with chronic respiratory failure (CRF) after initiation on home mechanical ventilation (HMV) via tracheostomy.
A retrospective cohort study of 109 HMV patients initiated and followed at an university-affiliated children’s hospital between 2003 and 2009. Patient characteristics are presented using descriptive statistics; generalized estimated equations are used to estimate adjusted odds ratios of select predictor variables for readmission.
The 12-month incidence of non-elective readmission was 40%. Close to half of these readmissions occurred within the first 3 months post-index discharge. Pneumonia and tracheitis were the most common reasons for readmission; 64% were pulmonary- or tracheostomy-related. Most demographic and clinical patient characteristics were not statistically associated with non-elective readmissions. Although, a change in the child’s management within 7 days before discharge was associated readmissions shortly after index discharge.
Non-elective readmissions of newly initiated pediatric HMV patients were common and likely multifactorial. Many of these readmissions were airway-related, and some may have been potentially preventable.
PMCID: PMC3694986  PMID: 21901855
readmission; home mechanical ventilation; tracheostomy; child
5.  Longitudinal Assessment of Hemoglobin Oxygen Saturation in Preterm and Term Infants in the First Six Months of Life 
The Journal of pediatrics  2011;159(3):377-383.e1.
To report longitudinal home recordings of hemoglobin O2 saturation by pulse oximetry (Spo2) during unperturbed sleep in preterm and term infants.
Study design
We recorded continuous pulse oximetry during the first 3 minutes of each hour of monitor use (non-event epochs) for 103 preterm infants born at <1750 g and ≤34 weeks postmenstrual age (PMA), and 99 healthy term infants.
Median baseline Spo2 was approximately 98% for both the preterm and term groups. Episodes of intermittent hypoxemia occurred in 74% of preterm and 62% of term infants. Among infants with intermittent hypoxemia, the number of seconds/hour of monitoring <90% Spo2 was initially significantly greater in the preterm than the term group and declined with age at a similar rate in both groups. The 75th to 95th percentiles for seconds/hour of Spo2 <90% in preterm infants were highest at 36 weeks PMA and progressively decreased until 44 weeks PMA, after which time they did not differ from term infants.
Clinically inapparent intermittent hypoxemia occurs in epochs unperturbed by and temporally unrelated to apnea or bradycardia events, especially in preterm infants at 36 to 44 weeks PMA.
PMCID: PMC3479632  PMID: 21481418
6.  Mutation of the cytosolic ribosomal protein-encoding RPS10B gene affects shoot meristematic function in Arabidopsis 
BMC Plant Biology  2012;12:160.
Plant cytosolic ribosomal proteins are encoded by small gene families. Mutants affecting these genes are often viable, but show growth and developmental defects, suggesting incomplete functional redundancy within the families. Dormancy to growth transitions, such as the activation of axillary buds in the shoot, are characterised by co-ordinated upregulation of ribosomal protein genes.
A recessive mutation in RPS10B, one of three Arabidopsis genes encoding the eukaryote-specific cytoplasmic ribosomal protein S10e, was found to suppress the excessive shoot branching mutant max2-1. rps10b-1 mildly affects the formation and separation of shoot lateral organs, including the shoot axillary meristems. Axillary meristem defects are enhanced when rps10b-1 is combined with mutations in REVOLUTA, AUXIN-RESISTANT1, PINOID or another suppressor of max2-1, FAR-RED ELONGATED HYPOCOTYL3. In some of these double mutants, the maintenance of the primary shoot meristem is also affected. In contrast, mutation of ALTERED MERISTEM PROGRAMME1 suppresses the rps10b-1axillary shoot defect. Defects in both axillary shoot formation and organ separation were enhanced by combining rps10b-1 with cuc3, a mutation affecting one of three Arabidopsis NAC transcription factor genes with partially redundant roles in these processes. To assess the effect of rps10b-1 on bud activation independently from bud formation, axillary bud outgrowth on excised cauline nodes was analysed. The outgrowth rate of untreated buds was reduced only slightly by rps10b-1 in both wild-type and max2-1 backgrounds. However, rps10b-1 strongly suppressed the auxin resistant outgrowth of max2-1 buds. A developmental phenotype of rps10b-1, reduced stamen number, was complemented by the cDNA of another family member, RPS10C, under the RPS10B promoter.
RPS10B promotes shoot branching mainly by promoting axillary shoot development. It contributes to organ boundary formation and leaf polarity, and sustains max2-1 bud outgrowth in the presence of auxin. These processes require the auxin response machinery and precise spatial distribution of auxin. The correct dosage of protein(s) involved in auxin-mediated patterning may be RPS10B-dependent. Inability of other RPS10 gene family members to maintain fully S10e levels might cause the rps10b-1 phenotype, as we found no evidence for unique functional specialisation of either RPS10B promoter or RPS10B protein.
PMCID: PMC3492191  PMID: 22963533
Shoot branching suppressor; S10e; Axillary bud; Leaf polarity; Lateral organ boundary; Auxin; Strigolactone; CUC; REV
7.  Sleep Fragmentation and Intermittent Hypoxemia Associated with Decreased Insulin Sensitivity in Obese Adolescent Latino Males 
Pediatric research  2012;72(3):293-298.
Although sleep-related breathing disorder (SRBD) has been linked to insulin resistance in adults, this has not been as well established in children. We hypothesized that the severity of SRBD in adolescents was associated with metabolic impairment.
Polysomnography was performed on obese, Latino males referred for snoring. The frequently sampled intravenous glucose tolerance test (FSIVGTT) was used to assess glucose homeostasis. Total body dual-energy X-ray absorptiometry (DEXA) was used to quantify adiposity.
22 males (mean age 13.4±SD 2.1 years, BMI z-score 2.4±0.3, obstructive apnea hypopnea index (OAHI) 4.1±3.2) were studied. After correcting for age and adiposity in multiple regression models, Log frequency of desaturation (defined as ≥3% drop in oxygen saturation from baseline) negatively correlated with insulin sensitivity. Sleep efficiency was positively correlated with glucose effectiveness (SG-the capacity of glucose to mediate its own disposal). The Log total arousal index was positively correlated with Log homeostasis model assessment (HOMA-IR).
Sleep fragmentation and intermittent hypoxemia are associated with metabolic impairment in obese adolescent Latino males independent of age and adiposity. We speculate that SRBD potentiates the risk for development of metabolic syndrome and type 2 diabetes in the obese adolescent population.
PMCID: PMC3427473  PMID: 22669298

Results 1-7 (7)