Owen Rennert - Academia.edu (original) (raw)
Papers by Owen Rennert
The Quarterly Review of Biology, Dec 1, 1997
Cortex, Nov 1, 2013
In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central ... more In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of
An analysis at the molecular level of gene action in develop ment allows multiple inferences to ... more An analysis at the molecular level of gene action in develop ment allows multiple inferences to be drawn concerning the activa tion of some of the cells' complement of genes and the repression of others. Mechanisms such as gene amplification, differential gene suppression and control at the translational level of protein biosynthesis all probably playa role in the phenomenon of cellular differentiation. The genetic control of multicellular aspects of development - formation of tissues and organs and interactions between them - are less well understood in molecular terms. The general principle is now well accepted that any agent which is capable of producing embryonic death may also, if the dosage and timing are appropriate, cause derangement of specific tissues, and result in congenital deformity. A second precept in the study of teratology is the observation that embryonic and fetal cells may not respond to drugs in precisely the same fashion as cells of the more mature organism. The temporal sequence of events during embryogenesis suggests
Pediatric Research, Apr 1, 1997
Molecular Psychiatry, Aug 6, 2013
We present a spatio-temporal assessment of microRNA expression throughout early human brain devel... more We present a spatio-temporal assessment of microRNA expression throughout early human brain development. We assessed the prefrontal cortex, hippocampus, and cerebellum of 18 normal human donor brains spanning infancy through adolescence by RNA-seq. We discovered differentially expressed microRNAs and broad microRNA patterns across both temporal and spatial dimensions, and between male and female prefrontal cortex. Putative target genes of the differentially expressed miRNAs were identified, which demonstrated functional enrichment for transcription regulation, synaptogenesis, and other basic intracellular processes. Sex-biased miRNAs also targeted genes related to Wnt and TGF-β pathways. The differentially expressed miRNA targets were highly enriched for gene sets related to autism, schizophrenia, bipolar disorder, and depression, but not neurodegenerative diseases, epilepsy, or other adult-onset psychiatric diseases. Our results suggest critical roles for the identified miRNAs in transcriptional networks of the developing human brain and neurodevelopmental disorders.
Pediatric Research, Apr 1, 1997
Supplementary Table S5 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S5 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S3 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S3 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Fig. S2 from Two types of human malignant melanoma cell lines revealed by expressio... more Supplementary Fig. S2 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S2 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S2 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S4 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S4 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Fig. S1 from Two types of human malignant melanoma cell lines revealed by expressio... more Supplementary Fig. S1 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S1 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S1 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Autism spectrum disorder (ASD) is a panoply of different diseases that share a set of common beha... more Autism spectrum disorder (ASD) is a panoply of different diseases that share a set of common behavioral traits, specifically social communication deficits, and repetitive and fixed/rigid functional patterns. The application of diagnostic technologies over the past 50 years resulted initially in the association of chromosomal mutations, and subsequently, in single gene defects and copy number variations (NCV) of the genome, and most recently, in variations in the whole genome sequence, resulting in the elucidation of syndromic and nonsyndromic ASD. At present, more than 800 gene mutations and 2300 CNVs have been associated with the pathophysiology of ASD. Contemporary research has focused on attempts to identify unifying molecular pathways (networks) to explain common behavior patterns among these different ASDs. These approaches are based on the postulation that synaptic transmission is aberrant, and that this phenomenon is initiated during fetal development, and results from an alt...
Pediatric Neurology, 2019
Background: The current classification system of neurodevelopmental disorders is based on clinica... more Background: The current classification system of neurodevelopmental disorders is based on clinical criteria; however, this method alone fails to incorporate what is now known about genomic similarities and differences between closely related clinical neurodevelopmental disorders. Here we present an alternative clinical molecular classification system of neurodevelopmental disorders based on shared molecular and cellular pathways, using syndromes with autistic features as examples. Methods: Using the Online Mendelian Inheritance in Man database, we identified 83 syndromes that had "autism" as a feature of disease, which in combination were associated with 69 autism disease-causing genes. Using annotation terms generated from the DAVID annotation tool, we grouped each gene and its associated autism syndrome into three biological pathways: ion transport, cellular synaptic function, and transcriptional regulation. Results: The majority of the autism syndromes we analyzed (54 of 83) enriched for processes related to transcriptional regulation and were associated with more non-neurologic symptoms and co-morbid psychiatric disease when compared with the other two pathways studied. Disorders with disrupted cellular synaptic function had significantly more motor-related symptoms when compared with the other groups of disorders. Conclusion: Our pathway-based classification system identified unique clinical characteristics within each group that may help guide clinical diagnosis, prognosis, and treatment. These results suggest that shifting current clinical classification of autism disorders toward molecularly driven, pathway-related diagnostic groups such as this may more precisely guide clinical decision making and may be informative for future clinical trial and drug development approaches.
Clinical Pharmacology & Therapeutics, 1966
Several variants of Hurler's syndrome can be distinguished both genetically and biochemically... more Several variants of Hurler's syndrome can be distinguished both genetically and biochemically. All these patients excrete excess acid mucopolysaccharides in their urine, but the ratio of chondroitin sulfate B to heparitin sulfate varies in different families. When the patients are in a basic condition and are maintained on a constant diet, the amount of 24 hour urinary acid mucopolysaccharides and the ratio of chondroitin sulfate B to heparitin sulfate show little daily fluctuation. Seven children with Hurler's syndrome were studied in their basic state and consecutively while receiving corticosteroids, thyroid, human growth hormone, hydroxychloroquine, and salicylates. It was demonstrated that administration of hydroxychloroquine increases urinary excretion of acid mucopolysaccharides, while prednisone tends to decrease the excretion of urinary acid mucopolysaccharides. Thyroid and corticosteroids produced marked changes in the ratio of chondroitin sulfate B to heparitin su...
Annals of the New York Academy of Sciences, 2004
Physiological chemistry and physics and medical NMR, 1983
Incubation of McCoy cultures with medium containing 14C-putrescine resulted in the incorporation ... more Incubation of McCoy cultures with medium containing 14C-putrescine resulted in the incorporation of 14C-polyamine into intracellular proteins. A greater than 100,000 dalton 14C-polyamine conjugated protein was present in the McCoy cell lysate supernatant (CLSP). CLSP was heterogeneous containing proteins with pIs ranging from 4.55 to 5.50. The major proteins had pIs of 4.55 and 5.20. Electrophoresis of solubilized McCoy cell lysate pellet revealed a 14C-polyamine conjugated protein peak with Mr approximately or equal to 70,000 (CLPP). Both CLSP and CLPP contained bound polyamine. The major CLSP polyamine was spermidine while spermine exceeded the other two polyamines (putrescine and spermidine) in CLPP. About 25% of the polyamines associated with CLSP and CLPP were covalently bound with the exception of CLSP putrescine where 62.1% was covalently bound. Results suggested the presence of a polyamine protein isopeptide bond in CLSP. Sephadex gel filtration of cultured medium resulted i...
Physiological chemistry and physics and medical NMR, 1983
polyamine conjugated proteins were identified in culture medium from both human skin fibroblasts ... more polyamine conjugated proteins were identified in culture medium from both human skin fibroblasts and transformed mouse cells (McCoy cells). Sephadex G-100 column chromatography of medium allowed identification of two polyamine conjugated proteins from both types of cell cultures; one with Mr greater than 100,000 (MP1) and one with Mr = 60,000-70,000 (MP2). Human skin fibroblast MP1 contained putrescine and spermidine while MP1 from McCoy cultures contained putrescine, spermidine and spermine. MP2 isolated from both cultures contained all three polyamines. The relative concentration of polyamines in MP1 and MP2 for human fibroblasts and McCoy cells were different. The spermidine and spermine associated with MP1 and MP2 of McCoy cultures was covalently bound while for putrescine only 70.5% in MP1 and MP2 of McCoy cultures was covalently bound while for putrescine only 70.5% in MP1 and 74.5% in MP2 was covalently bound. The covalent nature of the polyamine protein conjugation was confi...
The Quarterly Review of Biology, Dec 1, 1997
Cortex, Nov 1, 2013
In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central ... more In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of
An analysis at the molecular level of gene action in develop ment allows multiple inferences to ... more An analysis at the molecular level of gene action in develop ment allows multiple inferences to be drawn concerning the activa tion of some of the cells' complement of genes and the repression of others. Mechanisms such as gene amplification, differential gene suppression and control at the translational level of protein biosynthesis all probably playa role in the phenomenon of cellular differentiation. The genetic control of multicellular aspects of development - formation of tissues and organs and interactions between them - are less well understood in molecular terms. The general principle is now well accepted that any agent which is capable of producing embryonic death may also, if the dosage and timing are appropriate, cause derangement of specific tissues, and result in congenital deformity. A second precept in the study of teratology is the observation that embryonic and fetal cells may not respond to drugs in precisely the same fashion as cells of the more mature organism. The temporal sequence of events during embryogenesis suggests
Pediatric Research, Apr 1, 1997
Molecular Psychiatry, Aug 6, 2013
We present a spatio-temporal assessment of microRNA expression throughout early human brain devel... more We present a spatio-temporal assessment of microRNA expression throughout early human brain development. We assessed the prefrontal cortex, hippocampus, and cerebellum of 18 normal human donor brains spanning infancy through adolescence by RNA-seq. We discovered differentially expressed microRNAs and broad microRNA patterns across both temporal and spatial dimensions, and between male and female prefrontal cortex. Putative target genes of the differentially expressed miRNAs were identified, which demonstrated functional enrichment for transcription regulation, synaptogenesis, and other basic intracellular processes. Sex-biased miRNAs also targeted genes related to Wnt and TGF-β pathways. The differentially expressed miRNA targets were highly enriched for gene sets related to autism, schizophrenia, bipolar disorder, and depression, but not neurodegenerative diseases, epilepsy, or other adult-onset psychiatric diseases. Our results suggest critical roles for the identified miRNAs in transcriptional networks of the developing human brain and neurodevelopmental disorders.
Pediatric Research, Apr 1, 1997
Supplementary Table S5 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S5 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S3 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S3 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Fig. S2 from Two types of human malignant melanoma cell lines revealed by expressio... more Supplementary Fig. S2 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S2 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S2 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S4 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S4 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Fig. S1 from Two types of human malignant melanoma cell lines revealed by expressio... more Supplementary Fig. S1 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Supplementary Table S1 from Two types of human malignant melanoma cell lines revealed by expressi... more Supplementary Table S1 from Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Autism spectrum disorder (ASD) is a panoply of different diseases that share a set of common beha... more Autism spectrum disorder (ASD) is a panoply of different diseases that share a set of common behavioral traits, specifically social communication deficits, and repetitive and fixed/rigid functional patterns. The application of diagnostic technologies over the past 50 years resulted initially in the association of chromosomal mutations, and subsequently, in single gene defects and copy number variations (NCV) of the genome, and most recently, in variations in the whole genome sequence, resulting in the elucidation of syndromic and nonsyndromic ASD. At present, more than 800 gene mutations and 2300 CNVs have been associated with the pathophysiology of ASD. Contemporary research has focused on attempts to identify unifying molecular pathways (networks) to explain common behavior patterns among these different ASDs. These approaches are based on the postulation that synaptic transmission is aberrant, and that this phenomenon is initiated during fetal development, and results from an alt...
Pediatric Neurology, 2019
Background: The current classification system of neurodevelopmental disorders is based on clinica... more Background: The current classification system of neurodevelopmental disorders is based on clinical criteria; however, this method alone fails to incorporate what is now known about genomic similarities and differences between closely related clinical neurodevelopmental disorders. Here we present an alternative clinical molecular classification system of neurodevelopmental disorders based on shared molecular and cellular pathways, using syndromes with autistic features as examples. Methods: Using the Online Mendelian Inheritance in Man database, we identified 83 syndromes that had "autism" as a feature of disease, which in combination were associated with 69 autism disease-causing genes. Using annotation terms generated from the DAVID annotation tool, we grouped each gene and its associated autism syndrome into three biological pathways: ion transport, cellular synaptic function, and transcriptional regulation. Results: The majority of the autism syndromes we analyzed (54 of 83) enriched for processes related to transcriptional regulation and were associated with more non-neurologic symptoms and co-morbid psychiatric disease when compared with the other two pathways studied. Disorders with disrupted cellular synaptic function had significantly more motor-related symptoms when compared with the other groups of disorders. Conclusion: Our pathway-based classification system identified unique clinical characteristics within each group that may help guide clinical diagnosis, prognosis, and treatment. These results suggest that shifting current clinical classification of autism disorders toward molecularly driven, pathway-related diagnostic groups such as this may more precisely guide clinical decision making and may be informative for future clinical trial and drug development approaches.
Clinical Pharmacology & Therapeutics, 1966
Several variants of Hurler's syndrome can be distinguished both genetically and biochemically... more Several variants of Hurler's syndrome can be distinguished both genetically and biochemically. All these patients excrete excess acid mucopolysaccharides in their urine, but the ratio of chondroitin sulfate B to heparitin sulfate varies in different families. When the patients are in a basic condition and are maintained on a constant diet, the amount of 24 hour urinary acid mucopolysaccharides and the ratio of chondroitin sulfate B to heparitin sulfate show little daily fluctuation. Seven children with Hurler's syndrome were studied in their basic state and consecutively while receiving corticosteroids, thyroid, human growth hormone, hydroxychloroquine, and salicylates. It was demonstrated that administration of hydroxychloroquine increases urinary excretion of acid mucopolysaccharides, while prednisone tends to decrease the excretion of urinary acid mucopolysaccharides. Thyroid and corticosteroids produced marked changes in the ratio of chondroitin sulfate B to heparitin su...
Annals of the New York Academy of Sciences, 2004
Physiological chemistry and physics and medical NMR, 1983
Incubation of McCoy cultures with medium containing 14C-putrescine resulted in the incorporation ... more Incubation of McCoy cultures with medium containing 14C-putrescine resulted in the incorporation of 14C-polyamine into intracellular proteins. A greater than 100,000 dalton 14C-polyamine conjugated protein was present in the McCoy cell lysate supernatant (CLSP). CLSP was heterogeneous containing proteins with pIs ranging from 4.55 to 5.50. The major proteins had pIs of 4.55 and 5.20. Electrophoresis of solubilized McCoy cell lysate pellet revealed a 14C-polyamine conjugated protein peak with Mr approximately or equal to 70,000 (CLPP). Both CLSP and CLPP contained bound polyamine. The major CLSP polyamine was spermidine while spermine exceeded the other two polyamines (putrescine and spermidine) in CLPP. About 25% of the polyamines associated with CLSP and CLPP were covalently bound with the exception of CLSP putrescine where 62.1% was covalently bound. Results suggested the presence of a polyamine protein isopeptide bond in CLSP. Sephadex gel filtration of cultured medium resulted i...
Physiological chemistry and physics and medical NMR, 1983
polyamine conjugated proteins were identified in culture medium from both human skin fibroblasts ... more polyamine conjugated proteins were identified in culture medium from both human skin fibroblasts and transformed mouse cells (McCoy cells). Sephadex G-100 column chromatography of medium allowed identification of two polyamine conjugated proteins from both types of cell cultures; one with Mr greater than 100,000 (MP1) and one with Mr = 60,000-70,000 (MP2). Human skin fibroblast MP1 contained putrescine and spermidine while MP1 from McCoy cultures contained putrescine, spermidine and spermine. MP2 isolated from both cultures contained all three polyamines. The relative concentration of polyamines in MP1 and MP2 for human fibroblasts and McCoy cells were different. The spermidine and spermine associated with MP1 and MP2 of McCoy cultures was covalently bound while for putrescine only 70.5% in MP1 and MP2 of McCoy cultures was covalently bound while for putrescine only 70.5% in MP1 and 74.5% in MP2 was covalently bound. The covalent nature of the polyamine protein conjugation was confi...