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Articles 1 - 12 of 12
Full-Text Articles in Entire DC Network
Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young
Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young
Paediatrics Publications
Transforming growth factor beta (TGF-β) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell-type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem cells (ESCs), Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-β signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in nonmuscle cells is sufficient to redirect Smad3 to Myod1 sites. We …
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
Paediatrics Publications
This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by …
The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark
The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark
Paediatrics Publications
No abstract provided.
Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino
Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino
Paediatrics Publications
Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be …
Maternal Protein Restriction Elevates Cholesterol In Adult Rat Offspring Due To Repressive Changes In Histone Modifications At The Cholesterol 7Α-Hydroxylase Promoter, Gurjeev Sohi, Kelly Marchand, Andrew Revesz, Edith Arany, Daniel B. Hardy
Maternal Protein Restriction Elevates Cholesterol In Adult Rat Offspring Due To Repressive Changes In Histone Modifications At The Cholesterol 7Α-Hydroxylase Promoter, Gurjeev Sohi, Kelly Marchand, Andrew Revesz, Edith Arany, Daniel B. Hardy
Paediatrics Publications
Adverse events in utero, such as intrauterine growth restriction (IUGR), can permanently alter epigenetic mechanisms leading to the metabolic syndrome, which encompasses a variety of symptoms including augmented cholesterol. The major site for cholesterol homeostasis occurs via the actions of hepatic cholesterol 7α-hydroxylase (Cyp7a1), which catabolizes cholesterol to bile acids. To determine whether posttranslational histone modifications influence the long-term expression of Cyp7a1 in IUGR, we used a protein restriction model in rats. This diet during pregnancy and lactation led to IUGR offspring with decreased liver to body weight ratios, followed by increased circulating and hepatic cholesterol levels in both sexes …
Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier
Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier
Paediatrics Publications
The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3 and GSK-3β, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase …
Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng
Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng
Paediatrics Publications
Induction of tumour necrosis factor-α (TNF-α) expression leads to myocardial depression during sepsis. However, the underlying molecular mechanisms are not fully understood. The aim of this study was to investigate the role of Rac1 in TNF-α expression and cardiac dysfunction during endotoxemia and to determine the involvement of phosphoinositide-3 kinase (PI3K) in lipopolysaccharide (LPS)-induced Rac1 activation. Our results showed that LPS-induced Rac1 activation and TNF-α expression in cultured neonatal mouse cardiomyocytes. The response was inhibited in Rac1 deficient cardiomyocytes or by a dominant-negative Rac1 (Rac1N17). To determine whether PI3K regulates Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective …
Human Spinal Cord Injury Causes Specific Increases In Surface Expression Of Beta Integrins On Leukocytes, Feng Bao, Christopher S. Bailey, Kevin R. Gurr, Stewart I. Bailey, M. Patricia Rosas-Arellano, Arthur Brown, Gregory A. Dekaban, Lynne C. Weaver
Human Spinal Cord Injury Causes Specific Increases In Surface Expression Of Beta Integrins On Leukocytes, Feng Bao, Christopher S. Bailey, Kevin R. Gurr, Stewart I. Bailey, M. Patricia Rosas-Arellano, Arthur Brown, Gregory A. Dekaban, Lynne C. Weaver
Paediatrics Publications
Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for …
Hyperfiltration Affects Accuracy Of Creatinine Egfr Measurement, Shih Han S. Huang, Ajay P. Sharma, Abeer Yasin, Robert M. Lindsay, William F. Clark, Guido Filler
Hyperfiltration Affects Accuracy Of Creatinine Egfr Measurement, Shih Han S. Huang, Ajay P. Sharma, Abeer Yasin, Robert M. Lindsay, William F. Clark, Guido Filler
Paediatrics Publications
Background and objectives: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF). Design, setting, participants, & measurements: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF ( 131I-hippurate clearance) to calculate the FF (FF = GFR/ERPF). The eGFRs were calculated …
Integrin-Linked Kinase Is Required For Tgf-_1 Induction Of Dermal Myofibroblast Differentiation, Linda Vi, Cristina De Lasa, Gianna M. Diguglielmo, Lina Dagnino
Integrin-Linked Kinase Is Required For Tgf-_1 Induction Of Dermal Myofibroblast Differentiation, Linda Vi, Cristina De Lasa, Gianna M. Diguglielmo, Lina Dagnino
Paediatrics Publications
Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-b (TGF-b) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-b1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-b1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as a-smooth muscle actin. These alterations were not limited to Smad-associated TGF-b1 responses, as stimulation of noncanonical mitogenactivated protein kinase pathways by this growth …
Chest Compressions And Epinephrine During Resuscitation Of Infants Born At The Border Of Viability: Yes, No Or Maybe?, Gregory P. Moore, Thierry Daboval, Kevin W. Coughlin
Chest Compressions And Epinephrine During Resuscitation Of Infants Born At The Border Of Viability: Yes, No Or Maybe?, Gregory P. Moore, Thierry Daboval, Kevin W. Coughlin
Paediatrics Publications
Neonatology, in large part due to its population of babies born at the edge of viability, is rife with bioethical issues. This unique population is at high risk of mortality and considerable neurodevelopmental morbidity. One contentious, ongoing debate concerns whether these extremely low birth weight infants born at the border of viability should, if required by the Neonatal Resuscitation Program guidelines, receive chest compressions and epinephrine as part of their delivery room resuscitation. The present article, through a case presentation and discussion based on the ethical framework of principlism, provides readers with a thoughtful approach to the controversial issue of …
Histamine Deficiency Promotes Inflammation-Associated Carcinogenesis Through Reduced Myeloid Maturation And Accumulation Of Cd11b +Ly6g+ Immature Myeloid Cells, Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, Richard A. Friedman, Guangchun Jin, Heuijoon Park, Benjamin Shykind, Thomas G. Diacovo, Andras Falus, Timothy C. Wang
Histamine Deficiency Promotes Inflammation-Associated Carcinogenesis Through Reduced Myeloid Maturation And Accumulation Of Cd11b +Ly6g+ Immature Myeloid Cells, Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, Richard A. Friedman, Guangchun Jin, Heuijoon Park, Benjamin Shykind, Thomas G. Diacovo, Andras Falus, Timothy C. Wang
Paediatrics Publications
Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells, but its function in these cells is poorly understood. Here we show that Hdc-knockout mice show a high rate of colon and skin carcinogenesis. Using Hdc-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the Hdc promoter, we show that Hdc is expressed primarily in CD11b +Ly6G+ immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wild-type recipients results in increased CD11b + Ly6G + cell mobilization and reproduces the …