Abstract:
:We have previously discovered that the adult Drosophila melanogaster is tolerant to a low O2 environment, withstanding hours of total O2 deprivation without showing any evidence of cell injury. Subsequently, our laboratory embarked on the study of hypoxia tolerance using a mutagenesis and overexpression screens to begin to investigate loss-of-function or gain-of-function phenotypes. Both have given us promising results and, in this article, we detail some of the interesting results. Furthermore, several years ago, we have also started an experimental "Darwinian" selection to generate a fly strain that can perpetuate through all of its life cycle stages in hypoxic environments. Through microarrays and bioinformatic analyses, we have obtained genes (e.g. Notch pathway genes) that play an important role in hypoxia resistance. In addition, we also detail a proof of principle that Drosophila genes that are beneficial in fly resistance to hypoxia can also be as well in mammalian cells. We believe that the mechanisms that we are uncovering in Drosophila will allow us to gain insight regarding susceptibility and tolerance to low O2 and will therefore pave the way to develop better therapies for ailments that afflict humans as a consequence of low O2 delivery or low blood O2 levels.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Zhou D,Visk DW,Haddad GGdoi
10.1203/PDR.0b013e3181b27275subject
Has Abstractpub_date
2009-09-01 00:00:00pages
239-47issue
3eissn
0031-3998issn
1530-0447journal_volume
66pub_type
杂志文章,评审abstract::The mitochondrial DNA (mtDNA) point mutation T8993G has been associated with maternally inherited Leigh syndrome (MILS) when very abundant (> 95%). MILS patients are usually severely affected and die in early infancy. In 1993, a novel T8993C point mutation was described in a juvenile form of Leigh syndrome (LS) charac...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199605000-00028
更新日期:1996-05-01 00:00:00
abstract::Despite the availability of successful prevention strategies to prevent excessive hyperbilirubinemia, the neurological sequelae of bilirubin neurotoxicity (BNTx) still occur throughout the world. Kernicterus, encephalopathy due to BNTx, is now understood to be a spectrum of severity and phenotypes known as kernicterus...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1038/s41390-019-0608-0
更新日期:2020-01-01 00:00:00
abstract::The activity of lysozyme in saliva and serum was determined in 51 patients with cystic fibrosis. Measurements were made on two occasions at least 1 month apart and compared to those of 25 normal healthy individuals of the same ages, sex, and race. The mean serum lysozyme activity of normal individuals was 5.8 microgra...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198210000-00014
更新日期:1982-10-01 00:00:00
abstract:BACKGROUND:Childhood body mass index (BMI) trajectory classes are rarely linked to early puberty risk, particularly among Chinese children. We estimated early puberty risk across BMI trajectory classes, investigated factors contributing to pubertal development, and examined differences in final adult height between chi...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-019-0690-3
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:The effect of birth location on hypothermia-related outcomes has not been rigorously examined in the literature. In this study, we determined whether birth location had an impact on the benefits of whole-body cooling to 33.5 °C for 72 h in term infants (n = 208) with hypoxic-ischemic encephalopathy (HIE) who...
journal_title:Pediatric research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/pr.2012.103
更新日期:2012-10-01 00:00:00
abstract::The rat undergoes profound maturational changes in the intestinal structure and function during the third week of its life. To investigate the role of peripheral glucocorticoid metabolism in this process, we studied the postnatal maturation of intestinal structure and function. The peripheral metabolism of glucocortic...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000058923.08017.6F
更新日期:2003-05-01 00:00:00
abstract::Tolazoline is used in neonatal intensive care to treat hypoxia secondary to persistent pulmonary hypertension of the newborn. Its use is often complicated by systemic hypotension. We compared the effect of tolazoline-induced hypotension on organ blood flow, regional brain blood flow, and cerebral metabolism in hypoxic...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199008000-00007
更新日期:1990-08-01 00:00:00
abstract::Ca2+ transients were examined in embryonic chick hearts with an experimentally induced cardiac neural crest-related outflow tract defect known as persistent truncus arteriosus (PTA). In all of the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199712000-00002
更新日期:1997-12-01 00:00:00
abstract::Increased fetal lung expansion profoundly inhibits surfactant protein gene expression and stimulates cellular proliferation in the fetal lung. Our aim was to determine whether increased expansion of the lung after birth, by the application of a continuous positive airway pressure (CPAP) for 12 h, inhibits surfactant p...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200112000-00015
更新日期:2001-12-01 00:00:00
abstract::Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine,...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199112000-00017
更新日期:1991-12-01 00:00:00
abstract::Chondro-osseous tissue from five patients with diastropic dwarfism was studied by histologic, histochemical, and electron microscopic methods. The major abnormalities observed were: 1) irregular distribution of chondrocytes undergoing degeneration in the resting cartilage; 2) abnormal distribution of collagens in the ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197908000-00007
更新日期:1979-08-01 00:00:00
abstract::The widespread use of phototherapy for neonatal hyperbilirubinemia has caused some concern since substances other than bilirubin may be photoactivated. The toxic properties of these photoactivated substances might prove to be more harmful to the neonatal infant than bilirubin. The purpose of the present study was to i...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197503000-00009
更新日期:1975-03-01 00:00:00
abstract::The purpose of this study was to develop a strictly controlled chemical system in vitro to evaluate the efficacy of lead (Pb) chelators. Moreover, these experiments were carried out to understand further the complex interactions between Pb chelating agents, calcium-regulating hormones, and bone cell metabolism. The ef...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198004000-00014
更新日期:1980-04-01 00:00:00
abstract::Fetal and maternal plasma noradrenaline responses to invasive procedures were determined in pregnancies of 18 to 37 wk gestation. Fetal umbilical venous blood sampling was performed either from the placental cord insertion, which is not innervated, or the intrahepatic vein, which is innervated, and thus may be more st...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199904010-00007
更新日期:1999-04-01 00:00:00
abstract::There is increasing evidence that cortisol contributes to cardiovascular risk. It is unclear whether physiological concentrations of serum cortisol are related to vascular risk markers in children. The cross-sectional associations between morning serum cortisol and cardiovascular risk markers: blood pressure (BP) and ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181efc310
更新日期:2010-11-01 00:00:00
abstract::Data are scant regarding the development of cerebrovascular autoregulation in intrauterine growth-restricted (IUGR) newborns. We tested the hypothesis that IUGR improves the ability of neonates to withstand critical periods of gradual hemorrhagic hypotension by optimizing cerebrovascular autoregulation. Studies were c...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000139425.94975.77
更新日期:2004-10-01 00:00:00
abstract::Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance i...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199107000-00008
更新日期:1991-07-01 00:00:00
abstract::In vitro experiments were performed to examine the contractile responsiveness of guinea pig gallbladder smooth muscle as a function of developmental age. Gallbladder muscle strips from preterm (day 50-55 gestation), newborn (days 1-3 post partum), and 1-month-old animals were stimulated with agonists that initiate the...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198603000-00003
更新日期:1986-03-01 00:00:00
abstract::The precise mechanism by which the most common cause of bacterial enterocolitis in humans, Campylobacter jejuni, perturbs the intestinal mucosa remains elusive. To define effects of C. jejuni infection on mucosal permeability, Madin-Darby canine kidney (MDCK)-I and T84 cell monolayers were infected with C. jejuni for ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e31818702b9
更新日期:2008-12-01 00:00:00
abstract::Platelet volume was measured in 20 healthy children, 18 patients with acute idiopathic thrombocytopenic purpura (ITP), 24 patients with chronic ITP, 22 patients with aplastic anemia, and 17 patients with acute leukemia in childhood. The authors compared the platelet volume of these patients by use of peak platelet vol...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198002000-00013
更新日期:1980-02-01 00:00:00
abstract::Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed ener...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199703000-00024
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Bilirubin-induced neurologic dysfunction (BIND) is a spectrum of preventable neurological sequelae in jaundiced newborns. Current total plasma bilirubin (BT) concentration thresholds for phototherapy and/or exchange transfusion poorly predict BIND. METHODS:The unbound (free) bilirubin (Bf) measured at these...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1038/s41390-018-0010-3
更新日期:2018-10-01 00:00:00
abstract::Magnesium-deficient fetuses exhibited malformations (44%), anemia, and edema. Maternal plasma magnesium levels at day 21 of pregnancy reflected the level of dietary magnesium (2.43 +/- 0.09 mg Mg/100 ml, control; 0.74 +/- 0.02 mg Mg/100 ml, deficient). Plasma magnesium levels of deficient fetuses showed similar decrea...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197706000-00013
更新日期:1977-06-01 00:00:00
abstract::Energy and nitrogen balances were measured in growing low birthweight infants fed either mother's expressed breast milk or a 20 kcal per ounce formula to determine whether or not there were differences between the two dietary groups in (1) the partition of energy among excretion, expenditure, and storage and (2) the r...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198311000-00011
更新日期:1983-11-01 00:00:00
abstract::The isobutyryl-CoA dehydrogenase (IBD) enzyme is involved in the degradation of valine. IBD deficiency was first reported in 1998 and subsequent genetic investigations identified acyl-CoA dehydrogenase (ACAD) 8, now IBD, as the gene responsible for IBD deficiency. Only three individuals homozygous or compound heterozy...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000233085.72522.04
更新日期:2006-09-01 00:00:00
abstract::Hypoxic-ischemic (HI) injury in the preterm neonate incurs numerous functional deficits, however little is known about the neurochemically-defined brain nuclei that may underpin them. Key candidates are the brainstem catecholamine neurons. Using an immature animal model, the postnatal day (P)-3 (P3) rat pup, we invest...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181659774
更新日期:2008-04-01 00:00:00
abstract::Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency encountered in the neonatal intensive care unit. Despite advances in neonatal care, NEC remains a leading cause of morbidity and mortality among premature infants. Epidemiologic studies have identified multiple factors that ...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1203/PDR.0b013e31815ed64c
更新日期:2008-02-01 00:00:00
abstract::To determine the influence of an altered carotid body function on the laryngeal chemoreflex (LCR) response, reflex apnea was induced by laryngeal water stimulation during normoxia or acute hypoxia in unanesthetized awake lambs in which the ventilatory response to acute hypoxia was attenuated by prolonged postnatal hyp...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199312000-00024
更新日期:1993-12-01 00:00:00
abstract::The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of he...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199203000-00011
更新日期:1992-03-01 00:00:00
abstract::Cancer stem cells (CSC) are recently proposed to be the cancer initiating cells responsible for tumorigenesis and contribute to cancer resistance. Advances have been made in identifying and enriching CSC in leukemia and several solid tumors, including breast, brain and lung cancers. These studies suggest that, like no...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1203/01.pdr.0000203592.04530.06
更新日期:2006-04-01 00:00:00