45 results on '"Richardson SR"'
Search Results
2. Chief Judge James E. Baker U.S. Court of Appeals for the Armed Forces.
- Author
-
Richardson Sr., James S.
- Subjects
JUDGES ,TRAINING of lawyers ,MUNICIPAL services ,NATIONAL security - Abstract
The article offers professional profile of Chief Judge of the U.S. Court of Appeals for the Armed Forces (USCAAF) James E. Baker. Topics discussed include beginning of the legal training of Baker at the U.S. Marine Corps Platoon Leaders Class, after completion of graduation recruited as the second lieutenant in the U.S. Marine Corps and his aim of joining public services instead of the U.S. defense services. It further discusses his non-partisan approach to the national security.
- Published
- 2013
3. LETTER TO THE EDITOR.
- Author
-
Bomchill, Fern C., Baca, Lawrence R., Sales Lee, Juanita, Richardson Sr., James S., LaForge, William N., Kitchens, Joyce E., Del Toro, Russell A., McNew, Robert A., Goff, Jackie A., Berry, Adrienne A., Mueller, Robert C., Morse, Marvin H., Lazarus, Ellen M., Belcuore, Alfred F., Gilbert, Gerald E., Lilly, Thomas G., and Allard, David H.
- Subjects
JUDICIAL selection & appointment ,JUSTICE administration - Abstract
A letter to the editor is presented related to the symbiotic relation of Federal Bar Association (FBA) with the Federal Judiciary on the issues such as judicial appointments, fair compensation and rule changes for the administration of justice.
- Published
- 2016
4. Beneficial Effects of Cocoa Flavanols on Microvascular Responses in Young Men May Be Dependent on Ethnicity and Lifestyle.
- Author
-
Latif HM, Richardson SR, and Marshall JM
- Subjects
- Adolescent, Adult, Humans, Male, Young Adult, Acetylcholine pharmacology, Endothelium, Vascular drug effects, Flavonoids pharmacology, Forearm blood supply, Hyperemia, Microvessels drug effects, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Nitric Oxide Synthase metabolism, Skin blood supply, Skin drug effects, Skin metabolism, Stress, Psychological, Vasodilation drug effects, White People, South Asian People, Cacao chemistry, Chocolate, Life Style, Microcirculation drug effects
- Abstract
Cocoa flavan-3-ols affect endothelium-dependent responses in resistance vessels and microcirculation has received little attention. We tested the effects of dark chocolate consumption (396 mg total flavanols/day for 3 days) in two Groups of 10 men (18-25 years; non-smokers) each comprising equal numbers of White European (WE) and South Asian (SA) ethnicity. In Group 1, dark chocolate did not affect reactive hyperaemia in forearm muscle, but augmented muscle dilatation evoked by acute mental stress, and reactive hyperaemia and acetylcholine (ACh)-evoked dilatation in cutaneous microcirculation. Conversely, in Group 2, chocolate did not affect cutaneous reactive hyperaemia or ACh-evoked dilatation, but these responses were blunted in Group 1 relative to Group 2. Further, when Groups 1 and 2 were combined, responses were blunted in SAs relative to WEs, augmented by chocolate in SAs only. In Group 2 individuals whose ACh-evoked dilatation was attenuated by nitric oxide synthase (NOS) inhibition, ACh-evoked dilatation was not altered after chocolate, but the attenuating effect of NOS inhibition was lost. Conversely, in Group 2 individuals whose ACh-evoked dilatation was enhanced by NOS inhibition, ACh-evoked dilatation was also augmented by chocolate. We propose that in resistance and microvessels of young men, cocoa flavan-3-ols preferentially augment endothelium-dependent dilator responses whose responses are depressed by familial and lifestyle factors more prevalent in SAs than Wes. Flavan-3-ols may facilitate the NOS pathway but also influence other endothelium-dependent dilators.
- Published
- 2024
- Full Text
- View/download PDF
5. LINE-1 retrotransposons contribute to mouse PV interneuron development.
- Author
-
Bodea GO, Botto JM, Ferreiro ME, Sanchez-Luque FJ, de Los Rios Barreda J, Rasmussen J, Rahman MA, Fenlon LR, Jansz N, Gubert C, Gerdes P, Bodea LG, Ajjikuttira P, Da Costa Guevara DJ, Cumner L, Bell CC, Kozulin P, Billon V, Morell S, Kempen MHC, Love CJ, Saha K, Palmer LM, Ewing AD, Jhaveri DJ, Richardson SR, Hannan AJ, and Faulkner GJ
- Subjects
- Animals, Mice, Retroelements genetics, Male, Neurogenesis physiology, Neurogenesis genetics, Mice, Inbred C57BL, Gene Expression Regulation, Developmental genetics, Interneurons metabolism, Interneurons physiology, Long Interspersed Nucleotide Elements genetics, Parvalbumins metabolism
- Abstract
Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineages or therein promote neurodevelopmental gene expression. Here we report programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV) interneuron development. Mouse PV interneurons permit L1 mobilization in vitro and in vivo, harbor unmethylated L1 promoters and express full-length L1 mRNAs and proteins. Using nanopore long-read sequencing, we identify unmethylated L1s proximal to PV interneuron genes, including a novel L1 promoter-driven Caps2 transcript isoform that enhances neuron morphological complexity in vitro. These data highlight the contribution made by L1 cis-regulatory elements to PV interneuron development and transcriptome diversity, uncovered due to L1 mobility in this milieu., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
6. Every repeat is unique: Exploring the genomic impact of human L1 retrotransposons at locus-specific resolution.
- Author
-
Workman S and Richardson SR
- Subjects
- Humans, Genomics, Retroelements genetics, Long Interspersed Nucleotide Elements genetics
- Abstract
Fully understanding the impact of the human retrotransposon L1 requires that each of ∼500,000 L1 copies be evaluated as a potentially unique genomic entity. In this issue of Cell Genomics, Lanciano et al.
1 strive toward this goal, illuminating the reciprocal regulatory influence between individual L1s and their genomic integration sites., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
7. Safe Babies, Safe Moms: A Multifaceted, Trauma Informed Care Initiative.
- Author
-
Patchen L, McCullers A, Beach C, Browning M, Porter S, Danielson A, Asegieme E, Richardson SR, Jost A, Jensen CS, and Ahmed N
- Subjects
- Pregnancy, Infant, Infant, Newborn, Humans, Female, United States, Delivery of Health Care, Washington, Premature Birth
- Abstract
Purpose: This report describes a multifaceted, trauma-informed initiative developed to address racial/ethnic maternal and infant health inequities in Washington, D.C., Description: Structural racism and systemic oppression of marginalized communities have played a critical role in maternal and infant health inequities in the United States. Black birthing individuals are exponentially more likely to experience adverse birth outcomes, including preterm birth, low birth weight and maternal mortality. In response to these statistics, the Safe Babies Safe Moms (SBSM) initiative was developed to support patients of marginalized identities and improve health outcomes. SBSM Women's and Infants' Services Specialty Care (WIS-SC) is one component of this initiative focused on perinatal services., Assessment: SBSM WIS-SC includes trauma-informed clinical services, nurse navigation, lactation, diabetes and nutrition education, social work services, medical-legal services, and behavioral health support. Services are delivered by a multidisciplinary team trained on the following domains: (1) building connection within diverse care teams; (2) recognizing systemic barriers to trauma-informed approaches; (3) learning the brain science of implicit bias, trauma, and resilience; (4) Integrating self-care practices; and (5) acknowledging progress. Since the inception of the program, SBSM WIS-SC has served over 1500 patients., Conclusion: The SBSM WIS-SC intervention reflects a patient-centered approach to care, offering the multidisciplinary services required for perinatal patients with complex medical, psychosocial, and legal needs. Trauma informed training and team building is foundational to successful service delivery to address these multifaceted health needs of historically marginalized perinatal populations nationwide., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
8. Accuracy of Emergency Medicine Residents Using Point-of-Care Ultrasound (POCUS) to Detect Retained Stingray Barbs.
- Author
-
Richardson SR, Pope J, Dickson L, Hart LB, and Wilson C
- Subjects
- Humans, Animals, Swine, Point-of-Care Systems, Point-of-Care Testing, Ultrasonography, Skates, Fish, Emergency Medicine education, Foreign Bodies diagnostic imaging
- Abstract
Background: Stingray envenomation is a common presenting complaint for coastal emergency departments in the United States. Currently, radiograph is the gold standard to evaluate for a retained stingray barb, but ultrasound may be a useful tool to detect retained barbs., Objective: To determine if emergency medicine residents could use ultrasound to identify stingray barbs embedded in animal tissue models. A secondary objective was to determine if resident experience affected their ability to detect stingray barbs., Methods: Thirty-two emergency medicine residents participated in the study. After a short didactic session on foreign body identification with ultrasound, they rotated through six simulation stations and were asked to identify whether a stingray barb was present in pig and chicken tissue models. They were given 2 min per model to identify the presence, size, and depth of a stingray barb. Pre- and postexperiment surveys were collected to assess the residents' level of experience and confidence regarding foreign body identification using ultrasound., Results: Residents accurately identified barbs in chicken drumsticks with a sensitivity of 72.92% (95% confidence interval [CI] 63.89-81.48) and a specificity of 64.58% (95% CI 54.16-74.08), and in pig's feet with a sensitivity of 50.00% (95% CI 39.62-60.38) and specificity of 68.75% (95% CI 58.48-77.82). There was no statistically significant difference regarding accuracy for any outcome measured based on experience or level of training., Conclusions: The use of point-of-care ultrasound by novice sonographers lacks sensitivity to identify retained stingray barbs in animal models and is not significantly impacted by resident experience with point-of-care ultrasound., Competing Interests: Declaration of Competing Interest The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
9. Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development.
- Author
-
Gerdes P, Chan D, Lundberg M, Sanchez-Luque FJ, Bodea GO, Ewing AD, Faulkner GJ, and Richardson SR
- Subjects
- Mice, Animals, Retroelements genetics, DNA Methylation, Promoter Regions, Genetic, Embryonic Development, Long Interspersed Nucleotide Elements
- Abstract
Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability., (© 2023 Gerdes et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2023
- Full Text
- View/download PDF
10. Drowning rule-out with novices (DROWN) in ultrasound.
- Author
-
Richardson SR, Pope J, Hart LB, and Wilson CL
- Abstract
Objectives: Non-fatal drownings confer significant morbidity and mortality in the United States. Chest radiograph (CXR) is typically used as a screening modality for interstitial edema but lacks sensitivity early after submersion. No study has evaluated lung ultrasound in assessing for pulmonary edema after submersion events and we hypothesized that lung point-of-care (POC) ultrasound can identify interstitial edema in patients presenting after non-fatal drownings., Methods: Patients presenting to the emergency department after a submersion event were eligible if a CXR was obtained as part of their care. Emergency medicine residents performed a lung POC ultrasound and provided a "novice" interpretation of "normal" or "abnormal," which was independently reviewed by a blinded expert sonographer. Patients were contacted 2 weeks after presentation to assess for late sequela., Results: A prospective convenience sample of 59 patients included 21 adults (36%) and 38 children (64%) enrolled over 17 months with a median age of 6. Twenty-four (41%) patients had abnormalities on CXR. Of these, 20 patients had a positive ultrasound per novice interpretation. Compared to CXR, ultrasound had an overall sensitivity of 83% and a specificity of 66% for detecting pulmonary edema in non-fatal drownings. Notably, out of 35 subjects with a negative CXR, there were 12 (34%) cases with a positive lung ultrasound, 10 of which required hospital admission., Conclusion: Lung POC ultrasound has a moderate sensitivity and specificity when performed by novice sonographers to detect pulmonary edema presenting to an ED setting after a non-fatal drowning event., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)
- Published
- 2023
- Full Text
- View/download PDF
11. Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells.
- Author
-
Gerdes P, Lim SM, Ewing AD, Larcombe MR, Chan D, Sanchez-Luque FJ, Walker L, Carleton AL, James C, Knaupp AS, Carreira PE, Nefzger CM, Lister R, Richardson SR, Polo JM, and Faulkner GJ
- Subjects
- Humans, Mice, Animals, Retroelements genetics, DNA Transposable Elements genetics, Mutation, Long Interspersed Nucleotide Elements genetics, Induced Pluripotent Stem Cells
- Abstract
Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including examples intronic to Brca1 and Dmd. LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
12. Somatic retrotransposition in the developing rhesus macaque brain.
- Author
-
Billon V, Sanchez-Luque FJ, Rasmussen J, Bodea GO, Gerhardt DJ, Gerdes P, Cheetham SW, Schauer SN, Ajjikuttira P, Meyer TJ, Layman CE, Nevonen KA, Jansz N, Garcia-Perez JL, Richardson SR, Ewing AD, Carbone L, and Faulkner GJ
- Subjects
- Animals, DNA-Binding Proteins genetics, Macaca mulatta genetics, Neurons, Transcription Factors genetics, Brain, Long Interspersed Nucleotide Elements, Retroelements genetics
- Abstract
The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippocampal neurons from two rhesus macaques ( Macaca mulatta ). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5' transduction, and was present in ∼7% of hippocampal neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4 , a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution., (© 2022 Billon et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2022
- Full Text
- View/download PDF
13. Glucose 6 Phosphate Dehydrogenase Deficiency
- Author
-
Richardson SR and O'Malley GF
- Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme found in the cytoplasm of all cells in the body. It is a housekeeping enzyme that plays a vital role in the prevention of cellular damage from reactive oxygen species (ROS). It does this by providing substrates to prevent oxidative damage. Erythrocytes are particularly vulnerable to ROS due to their role in oxygen transport and inability to replace cellular proteins as mature cells. Inherited deficiencies of G6PD can result in acute hemolytic anemia during times of increased ROS production. This may be caused by stress or exposure to certain foods that contain high amounts of oxidative substances, for example, fava beans, or certain medications. In particular, anti-malarial agents have a strong association with inducing hemolytic anemia in patients with G6PD deficiency. Below are medications more commonly used in the United States that have been shown to trigger a hemolytic crisis in those with G6PD deficiency; however, a more comprehensive list of medications to be avoided has been published by the Italian G6PD Deficiency Association and can be found at www.g6pd.org. Common medications to be avoided or used with caution in G6PD-deficient patients include: Acetaminophen. Acetylsalicylic acid. Chloramphenicol. Chloroquine. Colchicine. Diaminodiphenyl sulfone. Diphenhydramine. Glyburide. Isoniazid. L-Dopa. Methylene blue. Nitrofurantoin. Phenazopyridine. Primaquine. Rasburicase. Streptomycin. Sulfacetamide. Sulfanilamide. Sulfapyridine. Sulfacytine. Sulfadiazine. Sulfaguanidine. Sulfamethoxazole. Sulfisoxazole. Trimethoprim. Tripelennamine. Vitamin K., (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
14. 50 shades of gray zone: A response to Dr. Fischer's ONSD Letter to the Editor.
- Author
-
Wilson C, Pope J, and Richardson SR
- Published
- 2021
- Full Text
- View/download PDF
15. Elderly woman with painless skin lesion of the right breast.
- Author
-
Richardson SR, Moen M, Murray K, and Wilson CL
- Published
- 2021
- Full Text
- View/download PDF
16. Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling.
- Author
-
Ewing AD, Smits N, Sanchez-Luque FJ, Faivre J, Brennan PM, Richardson SR, Cheetham SW, and Faulkner GJ
- Subjects
- Female, Gene Expression Profiling, Humans, Middle Aged, Organ Specificity, DNA Methylation, DNA Transposable Elements, DNA, Neoplasm genetics, DNA, Neoplasm metabolism, Epigenesis, Genetic, Epigenome, Gene Expression Regulation, Neoplastic, Long Interspersed Nucleotide Elements, Nanopore Sequencing, Neoplasms genetics, Neoplasms metabolism
- Abstract
Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu (SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
17. An unexpected ultrasound finding in a woman who passed out.
- Author
-
Richardson SR, Hardin J, and Wilson C
- Published
- 2020
- Full Text
- View/download PDF
18. LINE-1 Evasion of Epigenetic Repression in Humans.
- Author
-
Sanchez-Luque FJ, Kempen MHC, Gerdes P, Vargas-Landin DB, Richardson SR, Troskie RL, Jesuadian JS, Cheetham SW, Carreira PE, Salvador-Palomeque C, García-Cañadas M, Muñoz-Lopez M, Sanchez L, Lundberg M, Macia A, Heras SR, Brennan PM, Lister R, Garcia-Perez JL, Ewing AD, and Faulkner GJ
- Subjects
- Binding Sites genetics, DNA Methylation genetics, DNA-Binding Proteins genetics, Genome, Human genetics, Hippocampus metabolism, Humans, Liver metabolism, Neurons metabolism, Single-Cell Analysis, Epigenetic Repression genetics, Long Interspersed Nucleotide Elements genetics, Retroelements genetics, YY1 Transcription Factor genetics
- Abstract
Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
19. Evaluation of an electronic antimicrobial time-out on antimicrobial utilization at a large health system.
- Author
-
Richardson SR, Neuner EA, Athans V, Srinivas P, Wesolowski J, Gordon SM, and Fraser TG
- Subjects
- Academic Medical Centers, Aged, Anti-Infective Agents adverse effects, Electronic Health Records, Female, Humans, Male, Middle Aged, Retrospective Studies, Time Factors, Anti-Infective Agents therapeutic use, Antimicrobial Stewardship, Cross Infection drug therapy, Drug Utilization statistics & numerical data
- Abstract
We evaluated the impact of an electronic health record based 72-hour antimicrobial time-out (ATO) on antimicrobial utilization. We observed that 6 hours after the ATO, 21% of empiric antimicrobials were discontinued or de-escalated. There was a significant reduction in the duration of antimicrobial therapy but no impact on overall antimicrobial usage metrics.
- Published
- 2019
- Full Text
- View/download PDF
20. Dynamic Methylation of an L1 Transduction Family during Reprogramming and Neurodifferentiation.
- Author
-
Salvador-Palomeque C, Sanchez-Luque FJ, Fortuna PRJ, Ewing AD, Wolvetang EJ, Richardson SR, and Faulkner GJ
- Subjects
- Cells, Cultured, DNA Methylation genetics, Embryo, Mammalian metabolism, Germ Cells metabolism, Humans, Induced Pluripotent Stem Cells metabolism, Long Interspersed Nucleotide Elements physiology, Neurons metabolism, Promoter Regions, Genetic genetics, Retroelements genetics, Gene Expression Regulation, Developmental genetics, Long Interspersed Nucleotide Elements genetics, Neurogenesis genetics
- Abstract
The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neuronal lineage and cause somatic mosaicism. Although DNA methylation mediates L1 promoter repression, the temporal pattern of methylation applied to individual RC-L1s during neurogenesis is unclear. Here, we identified a de novo L1 insertion in a human induced pluripotent stem cell (hiPSC) line via retrotransposon capture sequencing (RC-seq). The L1 insertion was full-length and carried 5' and 3' transductions. The corresponding donor RC-L1 was part of a large and recently active L1 transduction family and was highly mobile in a cultured-cell L1 retrotransposition reporter assay. Notably, we observed distinct and dynamic DNA methylation profiles for the de novo L1 and members of its extended transduction family during neuronal differentiation. These experiments reveal how a de novo L1 insertion in a pluripotent stem cell is rapidly recognized and repressed, albeit incompletely, by the host genome during neurodifferentiation, while retaining potential for further retrotransposition., (Copyright © 2019 Salvador-Palomeque et al.)
- Published
- 2019
- Full Text
- View/download PDF
21. L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution.
- Author
-
Nguyen THM, Carreira PE, Sanchez-Luque FJ, Schauer SN, Fagg AC, Richardson SR, Davies CM, Jesuadian JS, Kempen MHC, Troskie RL, James C, Beaven EA, Wallis TP, Coward JIG, Chetty NP, Crandon AJ, Venter DJ, Armes JE, Perrin LC, Hooper JD, Ewing AD, Upton KR, and Faulkner GJ
- Subjects
- Antineoplastic Agents therapeutic use, Cell Line, Tumor, DNA Methylation, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Glycoproteins genetics, Glycoproteins metabolism, Humans, Loss of Heterozygosity genetics, Mutagenesis, Insertional, Mutation, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Evolution, Molecular, Long Interspersed Nucleotide Elements genetics, Ovarian Neoplasms pathology
- Abstract
LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
22. Heritable L1 Retrotransposition Events During Development: Understanding Their Origins: Examination of heritable, endogenous L1 retrotransposition in mice opens up exciting new questions and research directions.
- Author
-
Richardson SR and Faulkner GJ
- Subjects
- Animals, Embryo, Mammalian physiology, Germ Cells physiology, Humans, Mice, Mice, Transgenic, Embryonic Development genetics, Long Interspersed Nucleotide Elements genetics, Retroelements genetics
- Abstract
The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) has played a major role in shaping the sequence composition of the mammalian genome. In our recent publication, "Heritable L1 retrotransposition in the mouse primordial germline and early embryo," we systematically assessed the rate and developmental timing of de novo, heritable endogenous L1 insertions in mice. Such heritable retrotransposition events allow L1 to exert an ongoing influence upon genome evolution. Here, we place our findings in the context of earlier studies, and highlight how our results corroborate, and depart from, previous research based on human patient samples and transgenic mouse models harboring engineered L1 reporter genes. In parallel, we outline outstanding questions regarding the stage-specificity, regulation, and functional impact of embryonic and germline L1 retrotransposition, and propose avenues for future research in this field., (© 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
23. L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis.
- Author
-
Schauer SN, Carreira PE, Shukla R, Gerhardt DJ, Gerdes P, Sanchez-Luque FJ, Nicoli P, Kindlova M, Ghisletti S, Santos AD, Rapoud D, Samuel D, Faivre J, Ewing AD, Richardson SR, and Faulkner GJ
- Subjects
- ATP Binding Cassette Transporter, Subfamily B genetics, Adult, Aged, Aged, 80 and over, Animals, Cell Transformation, Neoplastic genetics, Female, Humans, Liver metabolism, Liver pathology, Male, Mammals genetics, Mice, Knockout, Middle Aged, Mutagenesis, Insertional, ATP-Binding Cassette Sub-Family B Member 4, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics, Long Interspersed Nucleotide Elements genetics, Retroelements genetics
- Abstract
The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2)
-/- mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including TF subfamily elements, and one GF subfamily example. One of the TF insertions carried a 3' transduction, allowing us to identify its donor L1 and to demonstrate that this full-length TF element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors., (© 2018 Schauer et al.; Published by Cold Spring Harbor Laboratory Press.)- Published
- 2018
- Full Text
- View/download PDF
24. Heritable L1 retrotransposition in the mouse primordial germline and early embryo.
- Author
-
Richardson SR, Gerdes P, Gerhardt DJ, Sanchez-Luque FJ, Bodea GO, Muñoz-Lopez M, Jesuadian JS, Kempen MHC, Carreira PE, Jeddeloh JA, Garcia-Perez JL, Kazazian HH Jr, Ewing AD, and Faulkner GJ
- Subjects
- Animals, Embryo, Mammalian cytology, Female, Genomics methods, Germ Cells, HeLa Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mosaicism, Whole Genome Sequencing methods, Embryo, Mammalian metabolism, Long Interspersed Nucleotide Elements
- Abstract
LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo., (© 2017 Richardson et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2017
- Full Text
- View/download PDF
25. TET enzymes: double agents in the transposable element-host genome conflict.
- Author
-
Gerdes P, Richardson SR, and Faulkner GJ
- Subjects
- Animals, DNA Methylation genetics, Epigenomics, Gene Expression Regulation genetics, Genome, Long Interspersed Nucleotide Elements genetics, Mice, Mouse Embryonic Stem Cells metabolism, Mouse Embryonic Stem Cells pathology, Regulatory Sequences, Nucleic Acid genetics, DNA-Binding Proteins genetics, Evolution, Molecular, Proto-Oncogene Proteins genetics, Retroelements genetics
- Abstract
The mouse genome is replete with retrotransposon sequences, from evolutionarily young elements with mutagenic potential that must be controlled, to inactive molecular fossils whose sequences can be domesticated over evolutionary time to benefit the host genome. In an exciting new study, de la Rica and colleagues have uncovered a complex relationship between ten-eleven translocation (TET) proteins and retrotransposons in mouse embryonic stem cells (ESCs), implicating TETs as enhancers in the exaptation and function of retroelement sequences. Furthermore, they have demonstrated that active demethylation of retrotransposons does not correlate with their increased expression in ESCs, calling into question long-held assumptions regarding the importance of DNA demethylation for retrotransposon expression, and revealing novel epigenetic players in retrotransposon control.Please see related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1096-8.
- Published
- 2016
- Full Text
- View/download PDF
26. Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme.
- Author
-
Carreira PE, Ewing AD, Li G, Schauer SN, Upton KR, Fagg AC, Morell S, Kindlova M, Gerdes P, Richardson SR, Li B, Gerhardt DJ, Wang J, Brennan PM, and Faulkner GJ
- Abstract
Background: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers., Results: Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu - Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines., Conclusions: These experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo.
- Published
- 2016
- Full Text
- View/download PDF
27. Transposable elements in the mammalian embryo: pioneers surviving through stealth and service.
- Author
-
Gerdes P, Richardson SR, Mager DL, and Faulkner GJ
- Subjects
- Animals, Cell Differentiation genetics, Endogenous Retroviruses genetics, Gene Expression Regulation, Developmental, Humans, DNA Transposable Elements, Embryonic Development genetics
- Abstract
Transposable elements (TEs) are notable drivers of genetic innovation. Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks. Conversely, ongoing TE-driven insertional mutagenesis, nonhomologous recombination, and other potentially deleterious processes can cause sporadic disease by disrupting genome integrity or inducing abrupt gene expression changes. Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome.
- Published
- 2016
- Full Text
- View/download PDF
28. LINE-1 Cultured Cell Retrotransposition Assay.
- Author
-
Kopera HC, Larson PA, Moldovan JB, Richardson SR, Liu Y, and Moran JV
- Subjects
- Alu Elements, Gene Expression, HeLa Cells, Humans, Retroelements, Transfection, Long Interspersed Nucleotide Elements
- Abstract
The Long INterspersed Element-1 (LINE-1 or L1) retrotransposition assay has facilitated the discovery and characterization of active (i.e., retrotransposition-competent) LINE-1 sequences from mammalian genomes. In this assay, an engineered LINE-1 containing a retrotransposition reporter cassette is transiently transfected into a cultured cell line. Expression of the reporter cassette, which occurs only after a successful round of retrotransposition, allows the detection and quantification of the LINE-1 retrotransposition efficiency. This assay has yielded insight into the mechanism of LINE-1 retrotransposition. It also has provided a greater understanding of how the cell regulates LINE-1 retrotransposition and how LINE-1 retrotransposition impacts the structure of mammalian genomes. Below, we provide a brief introduction to LINE-1 biology and then detail how the LINE-1 retrotransposition assay is performed in cultured mammalian cells.
- Published
- 2016
- Full Text
- View/download PDF
29. Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans.
- Author
-
Sanchez-Luque FJ, Richardson SR, and Faulkner GJ
- Subjects
- Computational Biology methods, Genomic Library, High-Throughput Nucleotide Sequencing, Humans, Long Interspersed Nucleotide Elements, Polymerase Chain Reaction, Reproducibility of Results, Genome, Human, Genomics methods, Retroelements
- Abstract
Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.
- Published
- 2016
- Full Text
- View/download PDF
30. Ubiquitous L1 mosaicism in hippocampal neurons.
- Author
-
Upton KR, Gerhardt DJ, Jesuadian JS, Richardson SR, Sánchez-Luque FJ, Bodea GO, Ewing AD, Salvador-Palomeque C, van der Knaap MS, Brennan PM, Vanderver A, and Faulkner GJ
- Subjects
- Genetic Variation, Humans, Neurogenesis, Polymerase Chain Reaction, Tissue Banks, Hippocampus cytology, Long Interspersed Nucleotide Elements, Mosaicism, Neurons cytology
- Abstract
Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source of genotypic variation among neurons. As a neurogenic niche, the hippocampus supports pronounced L1 activity. However, the basal parameters and biological impact of L1-driven mosaicism remain unclear. Here, we performed single-cell retrotransposon capture sequencing (RC-seq) on individual human hippocampal neurons and glia, as well as cortical neurons. An estimated 13.7 somatic L1 insertions occurred per hippocampal neuron and carried the sequence hallmarks of target-primed reverse transcription. Notably, hippocampal neuron L1 insertions were specifically enriched in transcribed neuronal stem cell enhancers and hippocampus genes, increasing their probability of functional relevance. In addition, bias against intronic L1 insertions sense oriented relative to their host gene was observed, perhaps indicating moderate selection against this configuration in vivo. These experiments demonstrate pervasive L1 mosaicism at genomic loci expressed in hippocampal neurons., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
31. The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.
- Author
-
Richardson SR, Doucet AJ, Kopera HC, Moldovan JB, Garcia-Perez JL, and Moran JV
- Subjects
- Animals, Genetic Diseases, Inborn, Humans, Mammals, Genetic Variation, Genome, Long Interspersed Nucleotide Elements, Recombination, Genetic, Short Interspersed Nucleotide Elements
- Abstract
Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.
- Published
- 2015
- Full Text
- View/download PDF
32. Diversity through duplication: whole-genome sequencing reveals novel gene retrocopies in the human population.
- Author
-
Richardson SR, Salvador-Palomeque C, and Faulkner GJ
- Subjects
- Humans, Gene Duplication, Genes, Genetic Variation, Genetics, Population, Genome, Human genetics, RNA, Messenger genetics, Sequence Analysis, DNA methods
- Abstract
Gene retrocopies are generated by reverse transcription and genomic integration of mRNA. As such, retrocopies present an important exception to the central dogma of molecular biology, and have substantially impacted the functional landscape of the metazoan genome. While an estimated 8,000-17,000 retrocopies exist in the human genome reference sequence, the extent of variation between individuals in terms of retrocopy content has remained largely unexplored. Three recent studies by Abyzov et al., Ewing et al. and Schrider et al. have exploited 1,000 Genomes Project Consortium data, as well as other sources of whole-genome sequencing data, to uncover novel gene retrocopies. Here, we compare the methods and results of these three studies, highlight the impact of retrocopies in human diversity and genome evolution, and speculate on the potential for somatic gene retrocopies to impact cancer etiology and genetic diversity among individual neurons in the mammalian brain., (© 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
33. APOBEC3A deaminates transiently exposed single-strand DNA during LINE-1 retrotransposition.
- Author
-
Richardson SR, Narvaiza I, Planegger RA, Weitzman MD, and Moran JV
- Subjects
- Deamination, Humans, Cytidine Deaminase metabolism, DNA, Single-Stranded metabolism, Long Interspersed Nucleotide Elements genetics, Proteins metabolism, Retroelements
- Abstract
Long INterspersed Element-1 (LINE-1 or L1) retrotransposition poses a mutagenic threat to human genomes. Human cells have therefore evolved strategies to regulate L1 retrotransposition. The APOBEC3 (A3) gene family consists of seven enzymes that catalyze deamination of cytidine nucleotides to uridine nucleotides (C-to-U) in single-strand DNA substrates. Among these enzymes, APOBEC3A (A3A) is the most potent inhibitor of L1 retrotransposition in cultured cell assays. However, previous characterization of L1 retrotransposition events generated in the presence of A3A did not yield evidence of deamination. Thus, the molecular mechanism by which A3A inhibits L1 retrotransposition has remained enigmatic. Here, we have used in vitro and in vivo assays to demonstrate that A3A can inhibit L1 retrotransposition by deaminating transiently exposed single-strand DNA that arises during the process of L1 integration. These data provide a mechanistic explanation of how the A3A cytidine deaminase protein can inhibit L1 retrotransposition.DOI: http://dx.doi.org/10.7554/eLife.02008.001., (Copyright © 2014, Richardson et al.)
- Published
- 2014
- Full Text
- View/download PDF
34. L1 retrotransposons and somatic mosaicism in the brain.
- Author
-
Richardson SR, Morell S, and Faulkner GJ
- Subjects
- Animals, Brain physiology, Drosophila, Humans, Rodentia, Long Interspersed Nucleotide Elements genetics, Mosaicism, Neurons physiology, Retroelements genetics
- Abstract
Long interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intraindividual genetic diversity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo. We compare experimental strategies used to map de novo somatic retrotransposition events and present the optimal criteria to identify a somatic L1 insertion. Finally, we discuss the unresolved impact of L1-mediated somatic mosaicism upon normal neurobiology, as well as its potential to drive neurological disease.
- Published
- 2014
- Full Text
- View/download PDF
35. L1 retrotransposons, cancer stem cells and oncogenesis.
- Author
-
Carreira PE, Richardson SR, and Faulkner GJ
- Subjects
- Animals, Humans, Neoplasms genetics, Cell Transformation, Neoplastic pathology, Neoplasms pathology, Neoplastic Stem Cells pathology, Retroelements genetics
- Abstract
Retrotransposons have played a central role in human genome evolution. The accumulation of heritable L1, Alu and SVA retrotransposon insertions continues to generate structural variation within and between populations, and can result in spontaneous genetic disease. Recent works have reported somatic L1 retrotransposition in tumours, which in some cases may contribute to oncogenesis. Intriguingly, L1 mobilization appears to occur almost exclusively in cancers of epithelial cell origin. In this review, we discuss how L1 retrotransposition could potentially trigger neoplastic transformation, based on the established correlation between L1 activity and cellular plasticity, and the proven capacity of L1-mediated insertional mutagenesis to decisively alter gene expression and functional output., (© 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.)
- Published
- 2014
- Full Text
- View/download PDF
36. Diffuse pulmonary neuroendocrine cell hyperplasia involving the chest wall.
- Author
-
Al-Ayoubi AM, Ralston JS, Richardson SR, and Denlinger CE
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma surgery, Aged, 80 and over, Biopsy, Needle, Carcinoid Tumor surgery, Carcinoma, Neuroendocrine diagnostic imaging, Carcinoma, Neuroendocrine pathology, Female, Follow-Up Studies, Humans, Hyperplasia pathology, Hyperplasia surgery, Immunohistochemistry, Lung Neoplasms diagnosis, Lung Neoplasms surgery, Pneumonectomy methods, Risk Assessment, Thoracic Surgery, Video-Assisted methods, Thoracic Wall diagnostic imaging, Thoracic Wall pathology, Tomography, X-Ray Computed methods, Treatment Outcome, Carcinoid Tumor diagnosis, Carcinoma, Neuroendocrine surgery, Incidental Findings, Neuroendocrine Cells pathology
- Abstract
Diffuse pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by a diffuse hypertrophy of neuroendocrine cells along the distal bronchioles. This condition is characterized by obstructive lung physiology and the development of small carcinoid tumors. We present a case of DIPNECH in a patient undergoing surgery for a primary lung adenocarcinoma. Interestingly, the chest wall also demonstrated involvement of DIPNECH indicated by the presence of small carcinoid tumors. The absence of any lung carcinoid tumor greater than 5 mm and the absence of lymph node metastases render the chest wall involvement unlikely to represent metastatic disease., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
37. Quality of life of formerly preterm and very low birth weight infants from preschool age to adulthood: a systematic review.
- Author
-
Zwicker JG and Harris SR
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Follow-Up Studies, Health Status, Humans, Infant, Extremely Low Birth Weight, Infant, Newborn, Infant, Premature, Infant, Very Low Birth Weight, Quality of Life
- Abstract
Objective: The goal of this systematic review was to synthesize studies that examined the health-related quality of life of preschool- and school-aged children, adolescents, and young adults who were born preterm and/or at very low birth weight., Methods: We searched 7 databases up to September 2006 (Medline, PubMed, Embase, EBM Reviews, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, and the Educational Resource Information Center) as well as gray literature sources. We independently screened studies and included them only if a quality-of-life outcome measure was used and findings compared preterm, very low birth weight, or extremely low birth weight infants with term or normal birth weight peers. We independently assessed the methodologic quality of each study by using criteria adapted from the Centre for Reviews and Dissemination., Results: Fifteen cohort or cross-sectional studies met the review criteria. In 6 studies of preschool-aged children, differences were found between study and control groups, suggesting that many preschool children born preterm or at very low birth weight perform more poorly than their peers in physical, emotional, and/or social functioning. Extremely low birth weight school-aged children had lower health utility scores compared with their peers, and similar results were found for adolescents. Parents of preterm and very low birth weight teens noted significantly poorer performance in their child's global health, behavior, and physical functioning, whereas the teenagers themselves did not. In young adulthood, differences in physical functioning remained, but subjective quality of life was similar to normal birth weight peers., Conclusions: The effects of preterm birth/very low birth weight on health-related quality of life seem to diminish over time, which possibly reflects issues related to a child's report versus a parent-proxy report, differing definitions of health-related quality of life, and adaptation of individuals over time, versus true change in health-related quality of life.
- Published
- 2008
- Full Text
- View/download PDF
38. Interventions for intermittent distance exotropia: review.
- Author
-
Gnanaraj L and Richardson SR
- Subjects
- Child, Child, Preschool, Chronic Disease, Exotropia surgery, Humans, Oculomotor Muscles surgery, Orthoptics, Patient Selection, Retrospective Studies, Strabismus etiology, Strabismus surgery, Strabismus therapy, Treatment Outcome, Vision Screening, Exotropia therapy
- Abstract
Purpose: Management decisions in intermittent distance exotropia vary and lack well-defined clinical guidelines. We undertook a systematic review in an attempt to clarify the effects of various surgical and nonsurgical treatments and to establish the significance of factors such as age with respect to outcome. The review was undertaken in collaboration with the Cochrane Eyes and Vision Group., Methods: Electronic and manual searches were undertaken to identify randomised controlled trials of surgical or nonsurgical treatments for intermittent distance exotropia. We also contacted researchers active in this field for information about further published or unpublished studies. There were no language restrictions. Study abstracts identified from the searches were analysed independently by the two reviewers (SR and LG) and marked for inclusion, exclusion, or consideration. Reviewer analysis was compared and full papers for appropriate studies were requested., Results: No randomised controlled trials were found that met our selection criteria., Conclusions: The current literature consists mainly of retrospective reviews. These are difficult to compare and analyse due to variations in definition, intervention criteria, and outcome measures. However, there appears to be an agreement that the nonsurgical treatment is more appropriate in small-angle deviations or as a supplement to surgery. Studies supporting both early and late surgical intervention were found, so the optimal timing of surgical intervention could not be concluded. There is a need for robust clinical trials to improve the evidence base for the management of this condition.
- Published
- 2005
- Full Text
- View/download PDF
39. Stereoacuity in unilateral visual impairment detected at preschool screening: outcomes from a randomized controlled trial.
- Author
-
Richardson SR, Wright CM, Hrisos S, Buck D, and Clarke MP
- Subjects
- Amblyopia diagnosis, Child, Preschool, Humans, Refractive Errors diagnosis, Vision Screening, Amblyopia therapy, Depth Perception physiology, Eyeglasses, Refractive Errors therapy, Sensory Deprivation, Vision Disorders physiopathology, Visual Acuity physiology
- Abstract
Purpose: Reduced stereoacuity is commonly found in association with reduced visual acuity or strabismus and may significantly affect neuro-developmental performance. Treatment for reduced visual acuity due to refractive error or amblyopia is believed to result in improved stereoacuity. This study was undertaken to investigate the effect on stereoacuity of treatment for unilateral visual impairment detected at preschool vision screenings, in the setting of a randomized controlled trial., Methods: Children identified through preschool vision screening were recruited and randomized to one of three groups (no treatment, glasses only, or full treatment with glasses and occlusion) for a period of 12 months, after which full treatment was given when indicated. Logarithm of the minimum angle of resolution (LogMAR) visual acuity and random-dot (Randot; Stereo Optical, Chicago, IL) stereoacuity were assessed at recruitment and at 12- and 18-month follow-ups by an orthoptist masked to group allocation., Results: One hundred seventy-seven children were recruited and randomized, 59 to each group. Comparison of stereoacuities showed an immediate median improvement of 30 seconds of arc in each group from refractive correction. Age significantly affected stereoacuity performance at recruitment (mean age, 4 years) but not at follow-up (mean age, 5 years). Deferring treatment did not affect final stereoacuity., Conclusions: In this group, stereoacuity improved to a normal level as a result of refractive correction. Children in whom treatment was deferred for 12 months did not demonstrate significantly poorer stereoacuity than those in treatment.
- Published
- 2005
- Full Text
- View/download PDF
40. Randomised controlled trial of treatment of unilateral visual impairment detected at preschool vision screening.
- Author
-
Clarke MP, Wright CM, Hrisos S, Anderson JD, Henderson J, and Richardson SR
- Subjects
- Amblyopia diagnosis, Amblyopia physiopathology, Child, Preschool, Follow-Up Studies, Humans, Patient Compliance, Single-Blind Method, Treatment Outcome, Vision Screening, Visual Acuity physiology, Amblyopia therapy, Bandages, Eyeglasses
- Abstract
Objectives: To test the efficacy of treatment for unilateral visual loss detected by preschool vision screening and the extent to which effectiveness varies with initial severity., Design: Randomised controlled trial of full treatment with glasses and patching, if required, compared with glasses only or no treatment. Masked assessment of best corrected acuity after one year of follow up., Setting: Eight UK eye departments., Participants: 177 children aged 3-5 years with mild to moderate unilateral impairment of acuity (6/9 to 6/36) detected by screening., Results: Children in the full and glasses treatment groups had incrementally better visual acuity at follow up than children who received no treatment, but the mean treatment effect between full and no treatment was equivalent to only one line on a Snellen chart (0.11 log units; 95% confidence interval 0.050 to 0.171; P < 0.0001). The effects of treatment depended on initial acuity: full treatment showed a substantial effect in the moderate acuity group (6/36 to 6/18 at recruitment) and no significant effect in the mild acuity group (6/9 to 6/12 at recruitment) (P = 0.006 for linear regression interaction term). For 64 children with moderate acuity loss the treatment effect was 0.20 log units, equivalent to one to two lines on a Snellen chart. When all children had received treatment, six months after the end of the trial, there was no significant difference in acuity between the groups., Conclusions: Treatment is worth while in children with the poorest acuity, but in children with mild (6/9 to 6/12) unilateral acuity loss there was little benefit. Delay in treatment until the age of 5 did not seem to influence effectiveness.
- Published
- 2003
- Full Text
- View/download PDF
41. Effects of nonylphenol ethoxylate exposure on reproductive output and bioindicators of environmental estrogen exposure in fathead minnows Pimephales promelas.
- Author
-
Nichols KM, Snyder EM, Snyder SA, Pierens SL, Miles-Richardson SR, and Giesy JP
- Subjects
- Animals, Biomarkers blood, Detergents toxicity, Environmental Exposure, Enzyme-Linked Immunosorbent Assay methods, Estradiol blood, Estrogens toxicity, Ethylene Glycols toxicity, Female, Fertility drug effects, Goldfish physiology, Male, Reproducibility of Results, Sex Factors, Testosterone blood, Vitellogenins biosynthesis, Vitellogenins blood, Cyprinidae physiology, Detergents pharmacology, Estrogens pharmacology, Ethylene Glycols pharmacology, Reproduction drug effects
- Abstract
Nonylphenol ethoxylates (NPEOs) were evaluated in the laboratory for potential effects on the reproductive physiology and fecundity of fathead minnows (Pimephales promelas). Groups of three adult male and three female fathead minnows were exposed in a continuous flow-through system to 0, 0.21, 0.65, 2.1, or 7.9 microg NPEO/L for 42 d. Rabbit anti-goldfish vitellogenin (VTG) antiserum was prepared and a competitive enzyme-linked immunosorbent assay (ELISA) was adapted for measurement of plasma VTG in fish following exposure. Plasma 17beta-estradiol (E2) and testosterone (T) were also quantified by ELISA at the end of the exposure. Neither survival nor fecundity of fathead minnows exhibited a concentration-dependent response to NPEOs. No significant differences were observed in plasma VTG concentrations among treatments for males or females. Mean plasma VTG concentrations in females ranged from 291.7 to 895.1 microg VTG/ml among treatments and did not overlap with mean concentrations measured in the plasma of males, which ranged from less than the method detection limit (0.27 microg VTG/ml) to 3.2 microg VTG/ml. Plasma E2 concentrations exhibited a significant difference between males and females within all NPEO treatments, but no differences were observed among treatments. Similarly, plasma T concentrations did not exhibit a concentration-dependent response to NPEOs.
- Published
- 2001
- Full Text
- View/download PDF
42. Effects of waterborne exposure to 4-nonylphenol and nonylphenol ethoxylate on secondary sex characteristics and gonads of fathead minnows (Pimephales promelas).
- Author
-
Miles-Richardson SR, Pierens SL, Nichols KM, Kramer VJ, Snyder EM, Snyder SA, Render JA, Fitzgerald SD, and Giesy JP
- Subjects
- Animals, Dose-Response Relationship, Drug, Female, Gonads growth & development, Gonads pathology, Male, Sex Determination Processes, Cyprinidae growth & development, Detergents toxicity, Ethylene Glycols toxicity, Gonads drug effects, Phenols toxicity, Water Pollutants, Chemical toxicity
- Abstract
Fathead minnows were exposed to 4-nonylphenol (NP) or nonylphenol ethoxylate (NPEO) to determine the effects of these weak estrogen agonists on secondary sex characteristics and gonads of sexually mature males and females during 42-day continuous-flow exposures. Neither NP nor NPEO caused statistically significant effects on tubercles or fatpad size at the concentrations tested. Exposure to 1. 1 or 3.4 micrograms NP/L caused changes in the number and size of Sertoli cells and germ cell syncytia. Necrotic aggregates of various stages of germ cells in the spermatogenic sequence were observed in the testes of males exposed to NP. Electron microscopy of the testes of NP-exposed males revealed the presence of phagocytic cells in the lumina of seminiferous tubules. The cytoplasm of some Sertoli cells was distended with myelin figures and necrotic spermatozoa. No significant effects on the stages of follicular development were observed in females exposed to NP. There were no differences in the gonads or secondary sex characteristics of males or females exposed to 5.5 micrograms NPEO/L, the greatest concentration studied. The histologic responses observed are sensitive indicators of waterborne exposure to NP at environmentally relevant concentrations, but not as sensitive as induction of plasma vitellogenin. The secondary sex characteristics were not affected by concentrations of NP or NPEO as great as 3.4 or 5.5 micrograms/L, respectively. Histologic responses occurred at concentrations that were less than the final chronic value based on survival and approximately the same as those required to cause effects on egg production. The histologic effects caused by NP were similar to, but not exactly the same as those caused by exposure of fathead minnows to 17 beta-estradiol., (Copyright 1999 Academic Press.)
- Published
- 1999
- Full Text
- View/download PDF
43. Intracellular acidification is not a prerequisite for glutamate-triggered death of cultured hippocampal neurons.
- Author
-
Wang GJ, Richardson SR, and Thayer SA
- Subjects
- Animals, Arachidonic Acid pharmacology, Calcium metabolism, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone toxicity, Cell Death drug effects, Cell Membrane drug effects, Cell Membrane metabolism, Cells, Cultured, Fluorometry, Hippocampus drug effects, Hippocampus ultrastructure, Hydrogen-Ion Concentration, Kinetics, Membrane Potentials drug effects, Mitochondria drug effects, Mitochondria physiology, Rats, Glutamic Acid toxicity, Hippocampus cytology, Neurons drug effects
- Abstract
Glutamate decreased intracellular pH (pHi) in cultured rat hippocampal neurons. The protonophore, FCCP (1 microM), produced an acidification comparable to that produced by glutamate. Application of glutamate to FCCP-treated cells, returned pHi to resting levels. This alkaline shift resulted from a glutamate-induced membrane depolarization that removed the driving force across the plasmalemma for H+ entry via FCCP. The endogenous protonophore, arachidonic acid (10 microM), produced pHi changes similar to those elicited by FCCP. Because application of glutamate and FCCP in combination did not change pHi, this treatment was used to determine the role of glutamate-induced acidification in neurotoxicity. FCCP (1 microM, 5 min) did not affect neuronal viability, either alone or in combination with various concentrations of glutamate, as indicated by the release of lactate dehydrogenase into the bathing medium. Thus, acidification was not the cause of glutamate-induced cell death although, it may be symptomatic of neurotoxic processes.
- Published
- 1995
- Full Text
- View/download PDF
44. Presentation of the president's gold key to Alpheua Maynard Phillips, M. D.
- Author
-
RICHARDSON CH Sr
- Subjects
- Humans, Gold, Medicine
- Published
- 1951
45. Myopia from an operational viewpoint.
- Author
-
RICHARDSON EF Sr
- Subjects
- Humans, Myopia
- Published
- 1950
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.