369 results on '"Bradley A. Carlson"'
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2. Macrophage Selenoproteins Restrict Intracellular Replication of Francisella tularensis and Are Essential for Host Immunity
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Rachel L. Markley, Katherine H. Restori, Bhuvana Katkere, Sarah E. Sumner, McKayla J. Nicol, Anastasia Tyryshkina, Shaneice K. Nettleford, David R. Williamson, David E. Place, Kalyan K. Dewan, Ashley E. Shay, Bradley A. Carlson, Santhosh Girirajan, K. Sandeep Prabhu, and Girish S. Kirimanjeswara
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selenium ,redox ,intracellular bacteria ,tularemia ,innate immunity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The essential micronutrient Selenium (Se) is co-translationally incorporated as selenocysteine into proteins. Selenoproteins contain one or more selenocysteines and are vital for optimum immunity. Interestingly, many pathogenic bacteria utilize Se for various biological processes suggesting that Se may play a role in bacterial pathogenesis. A previous study had speculated that Francisella tularensis, a facultative intracellular bacterium and the causative agent of tularemia, sequesters Se by upregulating Se-metabolism genes in type II alveolar epithelial cells. Therefore, we investigated the contribution of host vs. pathogen-associated selenoproteins in bacterial disease using F. tularensis as a model organism. We found that F. tularensis was devoid of any Se utilization traits, neither incorporated elemental Se, nor exhibited Se-dependent growth. However, 100% of Se-deficient mice (0.01 ppm Se), which express low levels of selenoproteins, succumbed to F. tularensis-live vaccine strain pulmonary challenge, whereas 50% of mice on Se-supplemented (0.4 ppm Se) and 25% of mice on Se-adequate (0.1 ppm Se) diet succumbed to infection. Median survival time for Se-deficient mice was 8 days post-infection while Se-supplemented and -adequate mice was 11.5 and >14 days post-infection, respectively. Se-deficient macrophages permitted significantly higher intracellular bacterial replication than Se-supplemented macrophages ex vivo, corroborating in vivo observations. Since Francisella replicates in alveolar macrophages during the acute phase of pneumonic infection, we hypothesized that macrophage-specific host selenoproteins may restrict replication and systemic spread of bacteria. F. tularensis infection led to an increased expression of several macrophage selenoproteins, suggesting their key role in limiting bacterial replication. Upon challenge with F. tularensis, mice lacking selenoproteins in macrophages (TrspM) displayed lower survival and increased bacterial burden in the lung and systemic tissues in comparison to WT littermate controls. Furthermore, macrophages from TrspM mice were unable to restrict bacterial replication ex vivo in comparison to macrophages from littermate controls. We herein describe a novel function of host macrophage-specific selenoproteins in restriction of intracellular bacterial replication. These data suggest that host selenoproteins may be considered as novel targets for modulating immune response to control a bacterial infection.
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- 2021
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3. The Essential Role of Selenoproteins in the Resolution of Citrobacter rodentium-Induced Intestinal Inflammation
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Shaneice K. Nettleford, Luming Zhao, Fenghua Qian, Morgan Herold, Brooke Arner, Dhimant Desai, Shantu Amin, Na Xiong, Vishal Singh, Bradley A. Carlson, and K. Sandeep Prabhu
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selenium ,cyclopentenone prostaglandins ,metabolism ,lamina propria ,enteric infection ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Enteropathogenic Escherichia coli (EPEC) leads to adverse colonic inflammation associated with poor resolution of inflammation and loss of epithelial integrity. Micronutrient trace element selenium (Se) is incorporated into selenoproteins as the 21st amino acid, selenocysteine (Sec). Previous studies have shown that such an incorporation of Sec into the selenoproteome is key for the anti-inflammatory functions of Se in macrophages and other immune cells. An intriguing mechanism underlying the anti-inflammatory and pro-resolving effects of Se stems from the ability of selenoproteins to skew arachidonic acid metabolism from pro-inflammatory mediators, prostaglandin E2 (PGE2) toward anti-inflammatory mediators derived from PGD2, such as 15-deoxy-Δ12, 14- prostaglandin J2 (15d-PGJ2), via eicosanoid class switching of bioactive lipids. The impact of Se and such an eicosanoid-class switching mechanism was tested in an enteric infection model of gut inflammation by C. rodentium, a murine equivalent of EPEC. C57BL/6 mice deficient in Se (Se-D) experienced higher mortality when compared to those on Se adequate (0.08 ppm Se) and Se supplemented (0.4 ppm Se) diets following infection. Decreased survival was associated with decreased group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) cells in colonic lamina propria of Se-D mice along with deceased expression of epithelial barrier protein Zo-1. Inhibition of metabolic inactivation of PGE2 by 15-prostaglandin dehydrogenase blocked the Se-dependent increase in ILC3 and Th17 cells in addition to reducing epithelial barrier integrity, as seen by increased systemic levels of FITC-dextran following oral administration; while 15d-PGJ2 administration in Se-D mice alleviated the effects by increasing ILC3 and Th17 cells. Mice lacking selenoproteins in monocyte/macrophages via the conditional deletion of the tRNA[Sec] showed increased mortality post infection. Our studies indicate a crucial role for dietary Se in the protection against inflammation following enteric infection via immune mechanisms involving epithelial barrier integrity.
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- 2020
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4. Female Mice with Selenocysteine tRNA Deletion in Agrp Neurons Maintain Leptin Sensitivity and Resist Weight Gain While on a High-Fat Diet
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Daniel J. Torres, Matthew W. Pitts, Lucia A. Seale, Ann C. Hashimoto, Katlyn J. An, Ashley N. Hanato, Katherine W. Hui, Stella Maris A. Remigio, Bradley A. Carlson, Dolph L. Hatfield, and Marla J. Berry
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selenium ,selenoprotein ,Trsp ,hypothalamus ,Agrp neuron ,sex differences ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis. There is also evidence that selenium supports leptin signaling in the hypothalamus by maintaining proper redox balance. In this study, we generated mice with conditional knockout of the selenocysteine tRNA[Ser]Sec gene (Trsp) in an orexigenic cell population called agouti-related peptide (Agrp)-positive neurons. We found that female TrspAgrpKO mice gain less weight while on a high-fat diet, which occurs due to changes in adipose tissue activity. Female TrspAgrpKO mice also retained hypothalamic sensitivity to leptin administration. Male mice were unaffected, however, highlighting the sexually dimorphic influence of selenium on neurobiology and energy homeostasis. These findings provide novel insight into the role of selenoproteins within a small yet heavily influential population of hypothalamic neurons.
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- 2021
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5. Identification of Signaling Pathways for Early Embryonic Lethality and Developmental Retardation in Sephs1−/− Mice
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Jeyoung Bang, Minguk Han, Tack-Jin Yoo, Lu Qiao, Jisu Jung, Jiwoon Na, Bradley A. Carlson, Vadim N. Gladyshev, Dolph L. Hatfield, Jin-Hong Kim, Lark Kyun Kim, and Byeong Jae Lee
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selenium ,selenoprotein ,SEPHS1 ,early embryogenesis ,embryonic lethality ,reactive oxygen species ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Selenophosphate synthetase 1 (SEPHS1) plays an essential role in cell growth and survival. However, the underlying molecular mechanisms remain unclear. In the present study, the pathways regulated by SEPHS1 during gastrulation were determined by bioinformatical analyses and experimental verification using systemic knockout mice targeting Sephs1. We found that the coagulation system and retinoic acid signaling were most highly affected by SEPHS1 deficiency throughout gastrulation. Gene expression patterns of altered embryo morphogenesis and inhibition of Wnt signaling were predicted with high probability at E6.5. These predictions were verified by structural abnormalities in the dermal layer of Sephs1−/− embryos. At E7.5, organogenesis and activation of prolactin signaling were predicted to be affected by Sephs1 knockout. Delay of head fold formation was observed in the Sephs1−/− embryos. At E8.5, gene expression associated with organ development and insulin-like growth hormone signaling that regulates organ growth during development was altered. Consistent with these observations, various morphological abnormalities of organs and axial rotation failure were observed. We also found that the gene sets related to redox homeostasis and apoptosis were gradually enriched in a time-dependent manner until E8.5. However, DNA damage and apoptosis markers were detected only when the Sephs1−/− embryos aged to E9.5. Our results suggest that SEPHS1 deficiency causes a gradual increase of oxidative stress which changes signaling pathways during gastrulation, and afterwards leads to apoptosis.
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- 2021
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6. Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
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Jisu Jung, Yoomin Kim, Jiwoon Na, Lu Qiao, Jeyoung Bang, Dongin Kwon, Tack-Jin Yoo, Donghyun Kang, Lark Kyun Kim, Bradley A. Carlson, Dolph L. Hatfield, Jin-Hong Kim, and Byeong Jae Lee
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selenium ,selenoprotein ,selenophosphate synthetase ,endothelial cell ,reactive oxygen species ,cell growth ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1-knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1-knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.
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- 2021
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7. Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
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Jessica A. Canter, Sarah E. Ernst, Kristin M. Peters, Bradley A. Carlson, Noelle R. J. Thielman, Lara Grysczyk, Precious Udofe, Yunkai Yu, Liang Cao, Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, and Petra A. Tsuji
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Selenof ,selenium ,selenoprotein ,colon cancer ,inflammation ,barrier integrity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
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- 2021
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8. Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes
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Lucia A. Seale, Ashley N. Ogawa-Wong, Ligia M. Watanabe, Vedbar S. Khadka, Mark Menor, Daniel J. Torres, Bradley A. Carlson, Dolph L. Hatfield, and Marla J. Berry
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Sec-tRNA[Ser]Sec ,selenoproteins ,brown adipose tissue ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA[Ser]Sec, encoded in mice by the gene Trsp. Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of Trsp in brown adipocytes (Trspf/f-Ucp1-Cre+/−), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, Trspf/f-Ucp1-Cre+/− mice maintain oxygen consumption and Ucp1 expression, with male Trspf/f-Ucp1-Cre+/− mice accumulating more triglycerides in BAT than both female Trspf/f-Ucp1-Cre+/− mice or Trspf/f controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in Trspf/f-Ucp1-Cre+/− mice. Microarray analysis of BAT from Trspf/f-Ucp1-Cre+/− mice revealed glutathione S-transferase alpha 3 (Gsta3) and ELMO domain containing 2 (Elmod2) as the transcripts most affected by the loss of Trsp. Male Trspf/f-Ucp1-Cre+/− mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trspf/f-Ucp1-Cre +/− mice implicate a mild thyroid hormone dysfunction in brown adipocytes.
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- 2021
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9. Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration
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Bradley A. Carlson, Ryuta Tobe, Elena Yefremova, Petra A. Tsuji, Victoria J. Hoffmann, Ulrich Schweizer, Vadim N. Gladyshev, Dolph L. Hatfield, and Marcus Conrad
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Selenoprotein ,Ferroptosis ,Lipid peroxidation ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes. Unlike Txnrd1- and Trsp-deficient mice, Gpx4−/− mice died shortly after birth and presented extensive hepatocyte degeneration. Similar to Txnrd1-deficient livers, Gpx4−/− livers manifested upregulation of nuclear factor (erythroid-derived)-like 2 (Nrf2) response genes. Remarkably, Gpx4−/− pups born from mothers fed a vitamin E-enriched diet survived, yet this protection was reversible as subsequent vitamin E deprivation caused death of Gpx4-deficient mice ~4 weeks thereafter. Abrogation of selenoprotein expression in Gpx4−/− mice did not result in viable mice, indicating that the combined deficiency aggravated the loss of Gpx4 in liver. By contrast, combined Trsp/Txnrd1-deficient mice were born, but had significantly shorter lifespans than either single knockout, suggesting that Txnrd1 plays an important role in supporting liver function of mice lacking Trsp. In sum our study demonstrates that the ferroptosis regulator Gpx4 is critical for hepatocyte survival and proper liver function, and that vitamin E can compensate for its loss by protecting cells against deleterious lipid peroxidation.
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- 2016
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10. Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice
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Petra A. Tsuji, Bradley A. Carlson, Christine B. Anderson, Harold E. Seifried, Dolph L. Hatfield, and Michael T. Howard
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IL-6 ,interferon-γ ,ribosome profiling ,selenium ,selenocysteine ,selenoprotein ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.
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- 2015
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11. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth
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Ryuta Tobe, Min-Hyuk Yoo, Bradley A. Carlson, Salvador Naranjo-Suarez, Petra A. Tsuji, and Cindy D. Davis
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HCT116 cells ,HT29 cells ,shRNA ,selenium ,cancer prevention ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins). Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15) may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.
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- 2011
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12. Mouse Models Targeting Selenocysteine tRNA Expression for Elucidating the Role of Selenoproteins in Health and Development
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Dolph L. Hatfield, Vadim N. Gladyshev, Petra A. Tsuji, Min-Hyuk Yoo, and Bradley A. Carlson
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mouse models ,selenium ,selenocysteine tRNA ,selenoproteins ,Organic chemistry ,QD241-441 - Abstract
Selenium (Se) deficiency has been known for many years to be associated with disease, impaired growth and a variety of other metabolic disorders in mammals. Only recently has the major role that Se-containing proteins, designated selenoproteins, play in many aspects of health and development begun to emerge. Se is incorporated into protein by way of the Se-containing amino acid, selenocysteine (Sec). The synthesis of selenoproteins is dependent on Sec tRNA for insertion of Sec, the 21st amino acid in the genetic code, into protein. We have taken advantage of this dependency to modulate the expression of Sec tRNA that in turn modulates the expression of selenoproteins by generating transgenic, conditional knockout, transgenic/standard knockout and transgenic/conditional knockout mouse models, all of which involve the Sec tRNA gene, to elucidate the intracellular roles of this protein class.
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- 2009
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13. Regulation of inflammation by selenium and selenoproteins: impact on eicosanoid biosynthesis
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S. A. Mattmiller, Bradley A. Carlson, and L. M. Sordillo
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Selenium ,Selenoproteins ,Eicosanoid biosynthesis ,Inflammation ,Nutrition. Foods and food supply ,TX341-641 ,Medicine - Abstract
Uncontrolled inflammation is a contributing factor to many leading causes of human morbidity and mortality including atherosclerosis, cancer and diabetes. Se is an essential nutrient in the mammalian diet that has some anti-inflammatory properties and, at sufficient amounts in the diet, has been shown to be protective in various inflammatory-based disease models. More recently, Se has been shown to alter the expression of eicosanoids that orchestrate the initiation, magnitude and resolution of inflammation. Many of the health benefits of Se are thought to be due to antioxidant and redox-regulating properties of certain selenoproteins. The present review will discuss the existing evidence that supports the concept that optimal Se intake can mitigate dysfunctional inflammatory responses, in part, through the regulation of eicosanoid metabolism. The ability of selenoproteins to alter the biosynthesis of eicosanoids by reducing oxidative stress and/or by modifying redox-regulated signalling pathways also will be discussed. Based on the current literature, however, it is clear that more research is necessary to uncover the specific beneficial mechanisms behind the anti-inflammatory properties of selenoproteins and other Se metabolites, especially as related to eicosanoid biosynthesis. A better understanding of the mechanisms involved in Se-mediated regulation of host inflammatory responses may lead to the development of dietary intervention strategies that take optimal advantage of its biological potency.
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- 2013
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14. Measles Vaccination Immunogenicity and Association with Caste in Chandigarh, India
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Abram L, Wagner, Joseph L, Mathew, Bradley F, Carlson, Aparna G, Kachoria, Bhavneet, Bharti, Vanita, Suri, and Matthew L, Boulton
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Infectious Diseases ,Social Class ,Virology ,Measles Vaccine ,Vaccination ,Humans ,Infant ,India ,Parasitology ,Antibodies, Viral ,Measles - Abstract
Measles affects those of lower socioeconomic status disproportionately. This study evaluated the impact of measles vaccination on antibody titers 3 months after vaccination across different socioeconomic groups, with a focus on caste. In total, 169 infants in Chandigarh, India, had serum samples collected immediately prior to vaccination at 9 months of age and 3 months later. Overall, 126 infants (76%) were seropositive (antibody titers > 12 mIU/mL), 26 (16%) were borderline (8–12 mIU/mL), and 14 (8%) were seronegative (< 8 mIU/mL). Seropositivity (versus borderline/seronegative infants) was 0.78 times as high among individuals from the historically marginalized scheduled castes/scheduled tribes compared with the others caste grouping (95% CI, 0.62–0.98). Antibody response was not tied to anthropometric measures but was attenuated among scheduled castes/scheduled tribes with higher incomes. This study provides observational evidence that social structures can be associated with individual immune responses.
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- 2022
15. Supplementary Table 1 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, Xue-Ming Xu, Min-Hyuk Yoo, Ping Ouyang, Bradley A. Carlson, Petra A. Tsuji, and Robert Irons
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Supplementary Table 1 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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- 2023
16. Data from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, Xue-Ming Xu, Min-Hyuk Yoo, Ping Ouyang, Bradley A. Carlson, Petra A. Tsuji, and Robert Irons
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Selenium has cancer-preventive activity that is mediated, in part, through selenoproteins. The role of the 15-kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with short hairpin RNA constructs targeting Sep15. Metabolic 75Se labeling and Northern and Western blot analyses revealed that >90% of Sep15 was downregulated. Growth of the resulting Sep15-deficient CT26 cells was reduced (P < 0.01), and cells formed significantly (P < 0.001) fewer colonies in soft agar compared with control CT26 cells. Whereas most (14 of 15) BALB/c mice injected with control cells developed tumors, few (3 of 30) mice injected with Sep15-deficient cells developed tumors (P < 0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases per mouse; however, mice injected with cells with downregulation of Sep15 only had 7.8 ± 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1,045 genes that were significantly (P < 0.001) affected by Sep15 deficiency. The highest-scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G2-M cell cycle arrest in cells with targeted downregulation of Sep15. In contrast to CT26 cells, Sep15-targeted downregulation in Lewis lung carcinoma (LLC1) cells did not affect anchorage-dependent or anchorage-independent cell growth. These data suggest tissue specificity in the cancer-protective effects of Sep15 downregulation, which are mediated, at least in part, by influencing the cell cycle. Cancer Prev Res; 3(5); 630–9. ©2010 AACR.
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- 2023
17. Supplementary Figure 1 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, Xue-Ming Xu, Min-Hyuk Yoo, Ping Ouyang, Bradley A. Carlson, Petra A. Tsuji, and Robert Irons
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Supplementary Figure 1 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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- 2023
18. Supplementary Figure 2 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, Xue-Ming Xu, Min-Hyuk Yoo, Ping Ouyang, Bradley A. Carlson, Petra A. Tsuji, and Robert Irons
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Supplementary Figure 2 from Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells
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- 2023
19. Direction of Alliaria petiolata (garlic mustard) leachate's effect on early litter mass loss is dependent upon saprotrophic community composition
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Charles A. Mettler and Bradley E. Carlson
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General Engineering - Published
- 2023
20. Monitoring the Seasonal Hydrology of Alpine Wetlands in Response to Snow Cover Dynamics and Summer Climate: A Novel Approach with Sentinel-2.
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Bradley Z. Carlson, Marie Hébert, Colin Van Reeth, Marjorie Bison, Idaline Laigle, and Anne Delestrade
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- 2020
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21. Trait Covariances in Eastern Box Turtles Do Not Support Pleiotropic Effects of the Melanocortin System on Color, Behavior, and Stress Physiology
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Bradley E. Carlson and William L. Robinson
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Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
22. Local environmental context drives heterogeneity of early succession dynamics in alpine glacier forefields
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Arthur Bayle, Bradley Z. Carlson, Anaïs Zimmer, Sophie Vallée, Antoine Rabatel, Edoardo Cremonese, Gianluca Filippa, Cédric Dentant, Christophe Randin, Andrea Mainetti, Erwan Roussel, Simon Gascoin, Dov Corenblit, Philippe Choler, Laboratoire de Géographie Physique et Environnementale (GEOLAB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut Sciences de l'Homme et de la Société (IR SHS UNILIM), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
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early succesion dynamics, glacier forefields ,[SDE]Environmental Sciences ,Ecology, Evolution, Behavior and Systematics ,Earth-Surface Processes - Abstract
Glacier forefields have long provided ecologists with a model to study patterns of plant succession following glacier retreat. While plant survey-based approaches applied along chronosequences provide invaluable information on plant communities, the “space-for-time” approach assumes environmental uniformity and equal ecological potential across sites and does not account for spatial variability in initial site conditions. Remote sensing provides a promising avenue for assessing plant colonisation dynamics using a so-called “real-time” approach. Here, we combined 36 years of Landsat imagery with extensive field sampling along chronosequences of deglaciation for eight glacier forefields in the south-western European Alps to investigate the heterogeneity of early plant succession dynamics. Based on the two complementary and independent approaches, we found strong variability in the time lag between deglaciation and colonisation by plants and in subsequent growth rates, and in the composition of early plant succession. All three parameters were highly dependent on the local environmental context, i.e., local vegetation surrounding the forefields and energy availability linked to temperature and snowmelt gradients. Potential geomorphological disturbance did not emerge as a strong predictor of succession parameters, perhaps due to insufficient spatial resolution of predictor variables. Notably, elapsed time since deglaciation showed no consistent relationship to plant assemblages, i.e., we did not identify a consistent order of successional species across forefields as a function of time. Overall, both approaches converged towards the conclusion that early plant succession is not stochastic as previous authors have suggested but rather deterministic. We discuss the importance of scale in deciphering the unique complexity of plant succession in glacier forefields and provide recommendations for improving botanical field surveys and using Landsat time series in glacier forefields systems. Our work demonstrates complementarity between remote sensing and field-based approaches for both understanding and predicting future patterns of plant succession in glacier forefields.
- Published
- 2022
23. Immunization status of children in Nepal and associated factors, 2016
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Pooja N. Patel, Manila Hada, Matthew L. Boulton, and Bradley F. Carlson
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Vaccination Coverage ,animal diseases ,media_common.quotation_subject ,Psychological intervention ,chemical and pharmacologic phenomena ,Disease ,Logistic regression ,Odds ,Nepal ,Environmental health ,Humans ,Medicine ,Child ,Empowerment ,media_common ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public Health, Environmental and Occupational Health ,biochemical phenomena, metabolism, and nutrition ,Vaccination ,Cross-Sectional Studies ,Infectious Diseases ,Socioeconomic Factors ,Immunization ,bacteria ,Molecular Medicine ,Female ,Immunization status ,business - Abstract
Background Nepal has made substantial improvements in childhood immunization uptake. However, vaccination levels are still below the country-specific Sustainable Development Goal target of 94.8% coverage by 2025 for children aged 12–23 months who received all immunizations recommended in the national immunization schedule by their first birthday. A better understanding of the predictors of full immunization can inform successful programmatic interventions to improve coverage while also guiding resource allocation to ensure all children are fully vaccinated. This study estimates childhood immunization coverage in Nepal and characterizes the association between immunization status and various sociodemographic predictors. Methods Data from the 2016 Nepal Demographic and Health Survey were used to examine the immunization status of children aged 12–23 months. Immunization status was categorized as fully immunized (receiving all recommended doses), under-immunized (receiving at least one, but not all, recommended doses), and un-immunized (not receiving any doses of any vaccine). Associations between full and under-immunization and potential sociodemographic predictors were assessed using logistic regression. Results Among 976 children, 78.2% were fully immunized, 21% were under-immunized, and 0.8% were un-immunized. Retention of an immunization card was significantly associated with full immunization status. Mothers who had completed a formal education above secondary school and mothers who were working at time of interview had increased odds of full immunization. Birthing in an institutional setting was also associated with higher odds of full immunization. Conclusions Overall, immunization coverage in Nepal is relatively high, although it varies by dose and sociodemographic factors. Almost 25% of Nepalese children were not fully immunized, leaving them at increased risk for vaccine-preventable disease related morbidity and mortality. Nepal must continue focused efforts to reach every child and minimize the equity gap; programs may focus on advocating for the use of immunization cards, education and empowerment for girls, and delivery in institutional settings.
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- 2021
24. Measles seroprevalence in persons over one year of age in Chandigarh, India
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Joseph L, Mathew, Dakota, Riopelle, R K, Ratho, Bhavneet, Bharti, Mini P, Singh, Vikas, Suri, Bradley F, Carlson, Abram L, Wagner, and Matthew L, Boulton
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Male ,Adult ,Pharmacology ,Vaccination Coverage ,Adolescent ,Vaccination ,Measles Vaccine ,Immunology ,Infant ,Antibodies, Viral ,Young Adult ,Cross-Sectional Studies ,Seroepidemiologic Studies ,Child, Preschool ,Humans ,Immunology and Allergy ,Female ,Child ,Aged ,Measles - Abstract
Measles continues to result in focal outbreaks in India, despite over three decades of universal infant vaccination. The aims of this study were to examine measles immunity in the population of Chandigarh, India, and to compare immunity by vaccination vs. natural infection. In a cross-sectional study of individuals 1-60 years selected from 30 communities within Chandigarh during 2017-2018, measles immunity was assessed using serological surveys. Seropositivity was compared across demographic groups, and by prior history of vaccination and natural history of infection. Among those 1-20 years old, measles seropositivity, and histories of measles vaccination or prior measles diagnosis were separately assessed as outcomes in logistic regression models, with demographic factors as independent variables. Among 1690 participants, 94% were seropositive, and 6% had borderline or negative antibody levels. Of those positive, 30% had prior vaccination, 16% had a history of natural infection, and 54% had an unknown history. Over 50% of individuals among those20 years old, had unknown history of immunity. In the multivariable regression models, vaccination was more common in younger ages (P .0001), and in males compared to females (P = .0220), and in those with more education (P .0001). The majority of the population was seropositive, and seropositivity increased with age. Older age groups were more likely to be protected because of previous natural infection, whereas younger age groups were protected by vaccination. There was inequity in vaccination coverage by gender, and maternal education status.
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- 2022
25. The role of selenoproteins in neutrophils during inflammation
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Tai-Jung Lee, Shaneice K. Nettleford, Allison McGlynn, Bradley A. Carlson, Girish S. Kirimanjeswara, and K. Sandeep Prabhu
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Lipopolysaccharides ,Inflammation ,Mice, Knockout ,Mice ,Neutrophils ,Biophysics ,Animals ,Reactive Oxygen Species ,Selenoproteins ,Molecular Biology ,Biochemistry - Abstract
Polymorphonuclear neutrophils (PMNs)-derived ROS are involved in the regulation of multiple functions of PMNs critical in both inflammation and its timely resolution. Selenium is an essential trace element that functions as a gatekeeper of cellular redox homeostasis in the form of selenoproteins. Despite their well-studied involvement in regulating functions of various immune cells, limited studies have focused on the regulation of selenoproteins in PMN and their associated functions. Ex-vivo treatment of murine primary bone marrow derived PMNs with bacterial endotoxin lipopolysaccharide (LPS) indicated temporal regulation of several selenoprotein genes at the mRNA level. However, only glutathione peroxidase 4 (Gpx4) was significantly upregulated, while Selenof, Selenow, and Gpx1 were significantly downregulated in a temporal manner at the protein level. Exposure of PMNs isolated from tRNA
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- 2022
26. Improved Mapping of Mountain Shrublands Using the Sentinel-2 Red-Edge Band.
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Arthur Bayle, Bradley Z. Carlson, Vincent Thierion, Marc Isenmann, and Philippe Choler
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- 2019
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27. Climatic Drivers of Greening Trends in the Alps.
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Gianluca Filippa, Edoardo Cremonese, Marta Galvagno, Michel Isabellon, Arthur Bayle, Philippe Choler, Bradley Z. Carlson, Simone Gabellani, Umberto Morra di Cella, and Mirco Migliavacca
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- 2019
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28. Citizen science reporting indicates geographic and phenotypic drivers of road use and mortality in a threatened rattlesnake
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Chaz Rhodes, Willard Haunfelder, and Bradley E Carlson
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Animal Science and Zoology - Abstract
Roads may influence the selection of phenotypic traits of wildlife. In particular, the likelihood of vehicle collisions with wildlife may vary depending on body coloration in contrast to the road, which may be exaggerated by cultural attitudes toward the species. The timber rattlesnake Crotalus horridus is a threatened species that varies widely in coloration, and their color pattern could influence thermoregulatory use of roads and visibility to motorists. Moreover, better-camouflaged snakes may have higher road mortality in areas where environmental interest is lower and, perhaps, negative attitudes toward wildlife are more prevalent. We used citizen scientist observations of timber rattlesnakes from iNaturalist and categorized for each rattlesnake the surface they were on, its color pattern, and whether they were alive. We combined iNaturalist data with Google Trends data to characterize regional variation in environmental interest. We discovered that lighter-colored snakes were more likely to be found on roads, as were snakes further south, west, and on warmer days. Once on a road, coloration did not influence survival regardless of road type or environmental interest. However, snakes on asphalt roads or on southern roads were more likely to be found dead. The higher likelihood of lighter-colored snakes being found on roads suggests that they are at a greater overall risk of road death, potentially selecting for darker coloration. Citizen scientist behavior may at least partly underlie the influence of latitude on the results, however, and further work in the application of citizen science data to such research questions is warranted.
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- 2022
29. Impact of Multiple Risk Factors on Vaccination Inequities: Analysis in Indian Infants Over 2 Decades
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Joseph L. Mathew, Bradley F. Carlson, and Deepti Bettampadi
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Male ,medicine.medical_specialty ,Epidemiology ,India ,01 natural sciences ,Measles ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,030212 general & internal medicine ,0101 mathematics ,Risk factor ,business.industry ,Diphtheria ,Public health ,Vaccination ,010102 general mathematics ,Public Health, Environmental and Occupational Health ,Infant ,medicine.disease ,Poliomyelitis ,Birth order ,Socioeconomic Factors ,Female ,Residence ,business ,Demography - Abstract
Introduction Several authors have explored the effect of individual risk factors on vaccination inequity in Indian infants. This study explores the combined impact of >1 risk factor on the probability of full vaccination. Methods The proportion of fully vaccinated infants (aged 1–2 years) was calculated from the National Family Health Survey conducted during 1997–1998 (National Family Health Survey-2, n=10,211), 2005–2006 (National Family Health Survey-3, n=9,582), and 2015–2016 (National Family Health Survey-4, n=48,715). Full vaccination was defined as receiving Bacille Calmette‒Guerin (1 dose); diphtheria, pertussis, tetanus (3 doses); oral polio (3 doses); and measles (1 dose) vaccines. The association between full vaccination status and 6 factors (infant sex, birth order, family wealth status, maternal education level, residence type, and religion) was analyzed individually, followed by the combined impact of ≥1 of the first 4, using logistic regression models. Results The AORs for full vaccination in the 3 surveys, respectively, were 1.09, 1.13, and 1.00 for male versus female infants; 0.68, 0.71, and 0.88 for birth order >1 versus birth order 1; 1.54, 1.96, and 1.20 for greater wealth versus lowest wealth stratum; 2.21, 2.27, and 1.27 for any maternal education versus none; 1.08, 1.10, and 1.08 for Hindu versus other religion; and 1.51, 1.10, and 0.88 for urban versus rural residence. The respective ORs of full vaccination in the 3 surveys by the number of risk factors were as follows: 1.26, 1.54, and 1.27 for 3 risk factors; 2.41, 3.23, and 1.68 for 2 risk factors; 4.42, 6.45, and 2.18 for 1 risk factor; and 7.32, 9.84, and 2.61 for no risk factor. Conclusions The presence of multiple risk factors had a cumulative negative impact on infant vaccination in India. Despite an improvement over 2 decades, significant inequities persist. Supplement information This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.
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- 2021
30. Power estimation for a submicron CMOS inverter driving a CRC interconnect load.
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Hung-Jung Chen and Bradley S. Carlson
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- 2000
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31. First report of rapid eye color change in a non‐avian tetrapod
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Chaz Rhodes, Keith Klein, and Bradley E. Carlson
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medicine.anatomical_structure ,law ,Evolutionary biology ,medicine ,Tetrapod (structure) ,Animal Science and Zoology ,Eye color change ,Turtle (robot) ,Iris (anatomy) ,Biology ,Ecology, Evolution, Behavior and Systematics ,law.invention - Published
- 2020
32. Long‐term behavioral repeatability in wild adult and captive juvenile turtles ( Terrapene carolina ): Implications for personality development
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Sasha J. Tetzlaff and Bradley E. Carlson
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0106 biological sciences ,education.field_of_study ,Boldness ,media_common.quotation_subject ,Personality development ,05 social sciences ,Population ,Captivity ,Zoology ,Biology ,010603 evolutionary biology ,01 natural sciences ,Intraspecific competition ,Personality ,Juvenile ,0501 psychology and cognitive sciences ,Animal Science and Zoology ,Temperament ,050102 behavioral science & comparative psychology ,education ,Ecology, Evolution, Behavior and Systematics ,media_common - Abstract
Animal personality can be defined as conspecific individuals consistently differing in behavioral tendencies. Personality is typically identified by behavioral repeatability, which occurs when within‐individual variance is low relative to among‐individual variance in the population. Intraspecific comparisons of behavioral repeatability in juveniles and adults within and across years are rare, but would be useful for testing hypotheses related to origins of animal personality and whether individuals exhibit stable or diverging behavior with ontogeny. To examine within‐ and across‐year behavioral repeatability for eastern box turtles (Terrapene carolina), we assessed boldness (movement latency after brief confinement) of captive‐born juveniles twice within three days when eight months old. We then repeated these tests for the same individuals one year later. Juveniles exhibited repeatable boldness within and across years. Although increasing body temperature was slightly associated with decreased movement latency, test year (1 or 2), or housing experience (being raised in an enriched or unenriched condition) had no effects on boldness. We also assessed across‐year repeatability of boldness (head emergence from the shell after brief confinement) for wild adults at 1–3 year intervals. Adults also exhibited repeatable across‐year boldness that was of similar magnitude to juveniles. We found no indication that sex class or whether adults had been radio‐tracked influenced boldness. Our results suggest eastern box turtles demonstrate consistent individuality in boldness from an early age that is largely unaffected by temporal or environmental variation, and these behavioral differences can be maintained for multiple years in captivity and the wild, contrasting with theoretical expectations for personality development. These findings add to recent accumulating evidence demonstrating juvenile and adult box turtles exhibit multiple repeatable behaviors over the short‐ and long‐term. We suggest this species is quickly gaining traction as a model organism for studying the proximate and ultimate causes of personality development within long‐lived animals.
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- 2020
33. In-situ Temperature Stations Elucidate Species’ Phenological Responses to Climate in the Alps, but Meteorological and Snow Reanalysis Facilitates Broad Scale and Long-Term Studies
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Idaline Laigle, Bradley Z. Carlson, Anne Delestrade, Marjorie Bison, Colin Van Reeth, and Nigel Gilles Yoccoz
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General Earth and Planetary Sciences - Abstract
Linking climate variability and change to the phenological response of species is particularly challenging in the context of mountainous terrain. In these environments, elevation and topography lead to a diversity of bioclimatic conditions at fine scales affecting species distribution and phenology. In order to quantify in situ climate conditions for mountain plants, the CREA (Research Center for Alpine Ecosystems) installed 82 temperature stations throughout the southwestern Alps, at different elevations and aspects. Dataloggers at each station provide local measurements of temperature at four heights (5 cm below the soil surface, at the soil surface, 30 cm above the soil surface, and 2 m above ground). Given the significant amount of effort required for station installation and maintenance, we tested whether meteorological data based on the S2M reanalysis could be used instead of station data. Comparison of the two datasets showed that some climate indices, including snow melt-out date and a heat wave index, can vary significantly according to data origin. More general indices such as daily temperature averages were more consistent across datasets, while threshold-based temperature indices showed somewhat lower agreement. Over a 12 year period, the phenological responses of four mountain tree species (ash (Fraxinus excelsior), spruce (Picea abies), hazel (Corylus avellana), birch (Betula pendula)), coal tits (Periparus ater) and common frogs (Rana temporaria) to climate variability were better explained, from both a statistical and ecological standpoint, by indices derived from field stations. Reanalysis data out-performed station data, however, for predicting larch (Larix decidua) budburst date. Overall, our study indicates that the choice of dataset for phenological monitoring ultimately depends on target bioclimatic variables and species, and also on the spatial and temporal scale of the study.
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- 2022
34. Parallel implementation of a unified approach to image focus and defocus analysis on the Parallel Virtual Machine.
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Yen-Fu Liu, Nai-Wei Lo, Murali Subbarao, and Bradley S. Carlson
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- 1998
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35. Analysis of reasons for loss to follow up in a prospective study in Chandigarh, India and impact from telecom changes
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Bhavneet Bharti, Pooja N. Patel, Vanita Suri, Abram L. Wagner, Bradley F. Carlson, Joseph L. Mathew, and Matthew L. Boulton
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Longitudinal study ,Science (General) ,QH301-705.5 ,India ,Loss to follow-up ,General Biochemistry, Genetics and Molecular Biology ,Q1-390 ,Phone ,Humans ,Medicine ,Attrition ,Longitudinal Studies ,Prospective Studies ,Biology (General) ,Prospective cohort study ,mHealth ,business.industry ,Infant ,General Medicine ,Service provider ,medicine.disease ,Research Note ,Incentive ,Telecommunications ,Female ,business ,Cell Phone ,Follow-Up Studies ,Cohort study - Abstract
Objective Mobile phones are used in research studies, to enroll and follow-up participants, collect data, and implement mHealth initiatives. We conducted a longitudinal study in a birth cohort, where infants were required to make four scheduled visits by 12 months of age. Families of those failing to attend scheduled follow-up visits, were contacted telephonically to ascertain the reasons, which were categorized as: not interested to continue participating, migrated, phone disconnected due to telecom change, or other reason. Results A total of 413 mother-infant dyads were enrolled. The overall attrition was 56%, with majority occurring at the first follow-up visit. This temporally coincided with a telecom service provider announcing strong incentives to switch providers. Attrition monotonically decreased at subsequent visits. The reasons were: moved away (13%), no longer interested (8%), phone disconnected (7%), and multiple other reasons (28%), the majority of whom had unreachable phones. Those who remained in the study and those lost to follow-up were similar on most demographic variables. Among common reasons for attrition in cohort studies, we experienced a new dimension introduced by telecom changes. These findings underscore the need to consider unexpected reasons for attrition in longitudinal studies, and design more robust methods to follow-up participants.
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- 2021
36. Critical Voltage Transition Logic: An Ultrafast CMOS Logic Family.
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Zhang Zhu and Bradley S. Carlson
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- 1997
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37. Transistor Chaining in CMOS Leaf Cells of Planar Topology.
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Bradley S. Carlson, C. Y. Roger Chen, and Dikran S. Meliksetian
- Published
- 1996
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38. Parallel logic simulation on a network of workstations using PVM.
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Maciek Kormicki, Ausif Mahmood, and Bradley S. Carlson
- Published
- 1996
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39. Synthesis of SEU-tolerant ASICs using concurrent error correction.
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Harry Hollander, Bradley S. Carlson, and Toby D. Bennett
- Published
- 1995
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40. Improved Lower Bounds for the Scheduling Optimization Problem.
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Yuan Hu and Bradley S. Carlson
- Published
- 1994
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41. A Unified Algorithm for Estimation and Scheduling in Data Path Synthesis.
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Yuan Hu and Bradley S. Carlson
- Published
- 1994
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42. Identification of Signaling Pathways for Early Embryonic Lethality and Developmental Retardation in Sephs1−/− Mice
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Lu Qiao, Tack-Jin Yoo, Dolph L. Hatfield, Jisu Jung, Byeong Jae Lee, Jin-Hong Kim, Bradley A. Carlson, Jiwoon Na, Jeyoung Bang, Vadim N. Gladyshev, Lark Kyun Kim, and Minguk Han
- Subjects
QH301-705.5 ,Retinoic acid ,Morphogenesis ,selenoprotein ,Biology ,medicine.disease_cause ,Article ,Catalysis ,Inorganic Chemistry ,chemistry.chemical_compound ,Mice ,Pregnancy ,medicine ,Animals ,Biology (General) ,Physical and Theoretical Chemistry ,selenium ,QD1-999 ,Molecular Biology ,Spectroscopy ,Mice, Knockout ,reactive oxygen species ,embryonic lethality ,Organic Chemistry ,Gastrulation ,Phosphotransferases ,Wnt signaling pathway ,Gene Expression Regulation, Developmental ,Embryo ,General Medicine ,Computer Science Applications ,Cell biology ,Mice, Inbred C57BL ,Chemistry ,early embryogenesis ,chemistry ,Knockout mouse ,Embryo Loss ,Female ,SEPHS1 ,Signal transduction ,Oxidative stress ,Gene Deletion ,Signal Transduction - Abstract
Selenophosphate synthetase 1 (SEPHS1) plays an essential role in cell growth and survival. However, the underlying molecular mechanisms remain unclear. In the present study, the pathways regulated by SEPHS1 during gastrulation were determined by bioinformatical analyses and experimental verification using systemic knockout mice targeting Sephs1. We found that the coagulation system and retinoic acid signaling were most highly affected by SEPHS1 deficiency throughout gastrulation. Gene expression patterns of altered embryo morphogenesis and inhibition of Wnt signaling were predicted with high probability at E6.5. These predictions were verified by structural abnormalities in the dermal layer of Sephs1−/− embryos. At E7.5, organogenesis and activation of prolactin signaling were predicted to be affected by Sephs1 knockout. Delay of head fold formation was observed in the Sephs1−/− embryos. At E8.5, gene expression associated with organ development and insulin-like growth hormone signaling that regulates organ growth during development was altered. Consistent with these observations, various morphological abnormalities of organs and axial rotation failure were observed. We also found that the gene sets related to redox homeostasis and apoptosis were gradually enriched in a time-dependent manner until E8.5. However, DNA damage and apoptosis markers were detected only when the Sephs1−/− embryos aged to E9.5. Our results suggest that SEPHS1 deficiency causes a gradual increase of oxidative stress which changes signaling pathways during gastrulation, and afterwards leads to apoptosis.
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- 2021
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43. Effects of the Herbicide Metolachlor and Fish Presence on Pond Mesocosm Communities
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Miguel Aguirre-Morales, Bradley E. Carlson, Justin Harmeson, William L. Robinson, and Charles A. Mettler
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biology ,Ecology ,Aquatic ecosystem ,Black crappie ,Pesticide ,biology.organism_classification ,Mesocosm ,chemistry.chemical_compound ,chemistry ,Ecosystem ,Periphyton ,Metolachlor ,Ecology, Evolution, Behavior and Systematics ,Apex predator - Abstract
The effects of many pesticides on aquatic ecosystems remain poorly understood, especially in naturalistic communities in which organisms are connected by a complex array of direct and indirect interactions. Moreover, multiple stressors can interact, and the addition of apex predators, such as fish, may introduce additional ecosystem changes that exacerbate or mitigate pesticide effects. Despite being both common and environmentally persistent, the effects of the herbicide metolachlor on realistic aquatic communities have received insufficient research attention. We tested the effects of metolachlor on pond mesocosms at three concentrations (0, 20, and 80 ppb), along with the presence vs. absence of fish (black crappie, Pomoxis nigromaculatus) to determine the independent and combined effects of these two environmental changes. We found both metolachlor and fish altered the pond mesocosms, but their effects did not interact. Metolachlor reduced phytoplankton as expected, but had nonlinear effects on dissolved oxygen. Metolachlor also altered tadpole behavior, making them less prone to hiding. Fish presence increased periphyton and decreased snail counts, as well as changing the behavior of tadpoles, reducing their hiding behavior. This work demonstrates previously undocumented effects of metolachlor in the presence and absence of fish and suggests future avenues of investigation.
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- 2021
44. Sensitivity of Landsat NDVI to subpixel vegetation and topographic components in glacier forefields: assessment from high-resolution multispectral UAV imagery
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Arthur Bayle, Géraud de Bouchard d’Aubeterre, Elise Fovet, Claire Brossard, Erwan Roussel, Bradley Z. Carlson, Franck Vautier, Dov Jean-François Corenblit, Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Géographie Physique et Environnementale (GEOLAB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut Sciences de l'Homme et de la Société (IR SHS UNILIM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre de Recherches sur les Ecosystèmes d'Altitude (CREA Mont-Blanc), Maison des Sciences de l’Homme de Clermont-Ferrand (MSH Clermont), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and Observatoire du Mont-Blanc
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geography ,geography.geographical_feature_category ,Pixel ,Multispectral image ,normalized difference vegetation index ,Glacier ,Ecological succession ,sensitivity ,Subpixel rendering ,Normalized Difference Vegetation Index ,glacier forefields ,topography ,Remote sensing (archaeology) ,[SDE]Environmental Sciences ,medicine ,unmanned aerial vehicle ,General Earth and Planetary Sciences ,[SDU.STU.GM]Sciences of the Universe [physics]/Earth Sciences/Geomorphology ,medicine.symptom ,Vegetation (pathology) ,Landsat ,Geology ,Remote sensing - Abstract
International audience; Recently, deglaciated landscapes are ideal natural arenas to investigate ecological succession processes. However, ground data acquisition remains complicated as glacier forefields are often difficult to access and fieldwork possibilities remain limited. Remote sensing offers an opportunity to bypass this issue and increase spatial and temporal coverage of ecological parameters. The Landsat satellites (5 to 8) provide reflectance data for the past 40 years, which align with recent phenomena of glacier retreat and related ecological and geomorphological dynamics in glacier forefields. Difficulties remain as information retrieved from 30-m Landsat pixels are the result of a mixture of objects influencing reflectance signals. Here, we used a submeter multispectral unmanned aerial vehicle (UAV) image of the Glacier noir foreland, France, to assess the sensitivity of Landsat normalized difference vegetation index (NDVI) to subpixel vegetation and topographic components. We found a twofold linear relationship (a ¼ 0.456) and high sensitivity between fractional vegetation cover (FVC) and Landsat NDVI with detection of low vegetation changes (FVC > 5%) at low NDVI values (
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- 2021
45. Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity
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Dolph L. Hatfield, Yunkai Yu, Petra A. Tsuji, Precious Udofe, Noelle R J Thielman, Kristin M. Peters, Vadim N. Gladyshev, Sarah E. Ernst, Liang Cao, Lara Grysczyk, Bradley A. Carlson, Jessica A Canter, and Cindy D. Davis
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Male ,Carcinogenesis ,Colorectal cancer ,SEP15 ,selenoprotein ,medicine.disease_cause ,Mice ,chemistry.chemical_compound ,Aberrant Crypt Foci ,Submucosa ,Intestinal Mucosa ,Biology (General) ,Selenoproteins ,selenium ,Spectroscopy ,Mice, Knockout ,chemistry.chemical_classification ,Dextran Sulfate ,General Medicine ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Chemistry ,medicine.anatomical_structure ,colon cancer ,Colonic Neoplasms ,Cytokines ,medicine.symptom ,Signal Transduction ,Aberrant crypt foci ,QH301-705.5 ,Azoxymethane ,Inflammation ,Biology ,Article ,Catalysis ,Inorganic Chemistry ,Sodium Selenite ,barrier integrity ,medicine ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,Selenof ,Organic Chemistry ,medicine.disease ,Diet ,Trace Elements ,Disease Models, Animal ,chemistry ,inflammation ,Cancer research ,Selenoprotein - Abstract
Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
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- 2021
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46. Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
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Jeyoung Bang, Dolph L. Hatfield, Lu Qiao, Tack-Jin Yoo, Yoomin Kim, Byeong Jae Lee, Lark Kyun Kim, Jisu Jung, Bradley A. Carlson, Jin-Hong Kim, Donghyun Kang, Jiwoon Na, and Dongin Kwon
- Subjects
QH301-705.5 ,SOD3 ,SOD1 ,selenoprotein ,Article ,Catalysis ,Cell Line ,Inorganic Chemistry ,Superoxide dismutase ,chemistry.chemical_compound ,angiogenesis ,Gene Knockout Techniques ,Mice ,Superoxides ,cell growth ,Animals ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,selenium ,QD1-999 ,Molecular Biology ,Spectroscopy ,chemistry.chemical_classification ,reactive oxygen species ,Reactive oxygen species ,biology ,Lipid peroxide ,Chemistry ,Cell growth ,Superoxide ,selenophosphate synthetase ,Organic Chemistry ,Phosphotransferases ,Endothelial Cells ,General Medicine ,Reactive Nitrogen Species ,Computer Science Applications ,Cell biology ,Endothelial stem cell ,Oxidative Stress ,HEK293 Cells ,biology.protein ,endothelial cell ,Lipid Peroxidation ,Gene Deletion - Abstract
The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1-knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1-knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.
- Published
- 2021
47. Lower Bounds on the Iteration Time and the Number of Resources for Functional Pipelined Data Flow Graphs.
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Yuan Hu, Ahmed Ghouse, and Bradley S. Carlson
- Published
- 1993
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48. Performance Enhancement of CMOS VLSI Circuits by Transistor Reordering.
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Bradley S. Carlson and C. Y. Roger Chen
- Published
- 1993
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49. Vaccine coverage, timeliness and delay estimated from regional and national cross-sectional surveys in Ethiopia, 2016
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Matthew L. Boulton, Brenda W. Gillespie, Bradley F. Carlson, Yemesrach A. Tefera, and Abram L. Wagner
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Male ,Time Factors ,Vaccination Coverage ,Ethiopia ,vaccine coverage ,vaccination timeliness ,vaccine delay ,Cross-sectional study ,Accelerated failure time model ,Logistic regression ,Pentavalent vaccine ,Linear regression ,Global health ,Humans ,Medicine ,Immunization Schedule ,Survival analysis ,Vaccines ,Models, Statistical ,Immunization Programs ,business.industry ,Research ,Vaccination ,Infant ,General Medicine ,Health Surveys ,Cross-Sectional Studies ,Child, Preschool ,Regression Analysis ,Female ,business ,Demography - Abstract
Introduction:measures of vaccine timing require data on vaccination dates, which may be unavailable. This study compares estimates of vaccine coverage and timing; and compares regression techniques that model these measures in the presence of incomplete data. Methods:this cross-sectional study used the 2016 Ethiopian Demographic and Health Survey (DHS), and a 2016 survey from Worabe, Ethiopia. Three measures of vaccine uptake were calculated: coverage (regardless of timing), timeliness (within 1 week of recommended administration), and delay (the number of days between the recommended and actual date of vaccination). Vaccine coverage and timeliness were modeled with logistic regressions. After excluding those without dates, vaccine delay was estimated using linear regression or survival analysis. Vaccine delay was also estimated using accelerated failure time (AFT) models. Results:the DHS survey included 3819 children aged 12-60 months and the Worabe survey included 484 children aged 12-23 months. In the Worabe survey, vaccine coverage for pentavalent vaccine dose 3 was 87.4%, with 8.6% receiving it within 1 week, and 71.7% within 4 weeks; the median delay was 19 days. Predictors of outcomes were similar in both the Worabe survey and Ethiopian DHS, with the largest numbers of significant associations seen in models with vaccine coverage or delays (with AFT models) as the outcomes. Conclusion:estimates of coverage may miss a substantial proportion of infants who have delayed vaccination. accelerated failure time (AFT) models are useful to estimate vaccine delay because they include information from all respondents (those with full and partial data on vaccination dates) and are agnostic about an age limit for timely vaccination.
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- 2021
50. Clinical Spectrum of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Protection From Symptomatic Reinfection
- Author
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Mahboob Chowdhury, Julio C Zuniga-Moya, Matthew C. Smith, Saira Saborio, Miguel Plazaola, Nery Sanchez, Carlos Barilla, Brenda Lopez, Hannah E Maier, Guillermina Kuan, Aubree Gordon, Anna M. Gajewski, John Kubale, Eva Harris, Sergio R. Ojeda, Angel Balmaseda, Bradley F. Carlson, Fausto Bustos Carrillo, and Roger Lopez
- Subjects
Microbiology (medical) ,Adult ,medicine.medical_specialty ,Adolescent ,CoV ,Population ,Disease ,based ,reinfection ,Young Adult ,Seroepidemiologic Studies ,Internal medicine ,Case fatality rate ,medicine ,Major Article ,Seroprevalence ,Humans ,Young adult ,education ,Child ,seropositive ,Aged ,Retrospective Studies ,SARS ,education.field_of_study ,business.industry ,SARS-CoV-2 ,Antibody titer ,COVID-19 ,cohort ,Titer ,Infectious Diseases ,AcademicSubjects/MED00290 ,Cohort ,community ,business - Abstract
Background There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings. Methods We followed 2338 people in Managua, Nicaragua, aged, A community-based cohort in Managua, Nicaragua, had very high severe acute respiratory syndrome coronavirus 2 seropositivity but lower-than-expected severity. Overall, 69% of infections were asymptomatic or subclinical and 1.1% of infections were severe. Seropositivity was associated with 93.6% protection from symptomatic reinfection through March 2021.
- Published
- 2021
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