136 results on '"Simons MJ"'
Search Results
2. TRENDS IN IMMUNOLOGICAL THERAPY
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Simons Mj
- Subjects
Immunity, Cellular ,Leukemia ,Lymphoma ,business.industry ,Immunologic Deficiency Syndromes ,Immunoglobulins ,General Medicine ,Computational biology ,Autoimmune Diseases ,Text mining ,Humans ,Medicine ,gamma-Globulins ,business ,Immunosuppressive Agents - Published
- 1970
3. ANICTERIC VIRAL HEPATITIS IN BLOOD DONORS: A CUNICO–PATHOLOGICAL AND AUSTRALIA ANTIGEN STUDY IN SINGAPORE
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Yap Eh, Ong Yw, Kwa Sb, Simons Mj, Fung Wp, and Tan Kk
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Anicteric viral hepatitis ,Antigen ,business.industry ,Medicine ,Clinico pathological ,General Medicine ,business ,Virology - Published
- 1971
4. HOW TO USE AN IMMUNOLOGY LABORATORY
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Simons Mj
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Uterine Diseases ,Immunity, Cellular ,business.industry ,Immunity ,Immunologic Deficiency Syndromes ,General Medicine ,Infections ,medicine.disease ,Rubella ,Autoimmune Diseases ,Agammaglobulinemia ,Allergy and Immunology ,Neoplasms ,Immunology ,Hypersensitivity ,Humans ,Medicine ,Female ,Laboratories ,business - Published
- 1970
5. Streptokinase and ejection fraction after myocardial infarction
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Vandenbogaerde Jf and Simons Mj
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Streptokinase ,Myocardial Infarction ,Stroke Volume ,General Medicine ,medicine.disease ,Internal medicine ,medicine ,Cardiology ,Humans ,Myocardial infarction ,business ,medicine.drug - Published
- 1988
6. The current status of IgE in allergic reactions
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Hosking Cs, Simons Mj, and Hogarth-Scott Rs
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Erythrocytes ,biology ,business.industry ,Radioimmunoassay ,General Medicine ,Haplorhini ,History, 20th Century ,Immunoglobulin E ,Antigen-Antibody Reactions ,Iodine Radioisotopes ,Immunoglobulin M ,Immunoglobulin G ,Immunology ,biology.protein ,Hypersensitivity ,Medicine ,Animals ,Humans ,gamma-Globulins ,Current (fluid) ,business - Published
- 1970
7. TROPICAL IMMUNOLOGY DEVELOPS IN AUSTRALIA
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Stanley Nf and Simons Mj
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medicine.medical_specialty ,Geography ,Allergy and Immunology ,Research ,Tropical Medicine ,Tropical medicine ,Australia ,medicine ,Library science ,General Medicine ,Societies, Medical - Published
- 1977
8. OffPeak. The Harvard guide to women's health.
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Simons MJ
- Published
- 1998
9. Characterization of Ethos therapy systems for adaptive radiation therapy: A multi-machine comparison.
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van de Schoot AJ, Hoffmans D, van Ingen KM, Simons MJ, and Wiersma J
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- Humans, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy Dosage, Radiometry, Phantoms, Imaging, Particle Accelerators, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: The recently released Ethos therapy system (Varian Medical Systems) allows for online CBCT-guided adaptive radiation therapy (RT). The clinical introduction of multiple systems requires machine characterization and machine variation quantification to allow patient interchangeability between systems. Despite several clinical introductions, limited vendor-independent information on machine performance is available. Our aim was to determine the relevant dosimetric and mechanical characteristics of individual machines and to quantify machine variations., Methods: Six Ethos treatment machines, equipped with a 6-MV FFF beam including dual-layer MLC and kV-CBCT system, were recently introduced clinically after extensive machine characterization and pre-configured beam model verification. Point doses and profiles were measured and compared to vendor-provided reference data and dose calculations. Also, dose calculations were verified based on point measurements for non-standard fields and dose distributions for optimized treatment plans. Agreements between dose profiles (dose distributions) were quantified using 1D (3D) γ-analysis. Additionally, we quantified leaf transmission, dosimetric leaf gap (DLG) and couch attenuation, determined isocenter accuracy and kV-MV isocenter coincidence and verified the kV-CBCT system. Machine variations were quantified for all dosimetric and mechanical characteristics., Results: For all machines, distinct agreements were found between measurements and vendor-provided reference data as well as measurements and dose calculations. Mean γ
1%/1mm values for all profiles were below 0.30. All profiles, point measurements and dose distributions matched well among the six machines. Minimal machine variations were found in terms of DLG (0.05 mm), leaf transmission (0.001%), isocenter accuracy (0.08 mm), kV-MV isocenter coincidence (0.15 mm), couch attenuation (0.69%), and CBCT imaging dose (0.29 mGy)., Conclusions: This study demonstrates excellent agreement between individual Ethos therapy systems and vendor-provided reference data as well as a pre-configured beam model. Furthermore, our results show good consistency among all machines and provide valuable insights on relevant machine characteristics. The systematically obtained results provide benchmark data for future clinical introduction of Ethos therapy systems., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)- Published
- 2023
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10. Unique Interferon Pathway Regulation by the Andes Virus Nucleocapsid Protein Is Conferred by Phosphorylation of Serine 386.
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Simons MJ, Gorbunova EE, and Mackow ER
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- Animals, Chlorocebus aethiops, Endothelial Cells virology, HEK293 Cells, Orthohantavirus pathogenicity, Hantavirus Infections virology, Host-Pathogen Interactions, Humans, Interferon-beta physiology, Interferons metabolism, Interferons physiology, Nucleocapsid Proteins physiology, Phosphorylation, Protein Serine-Threonine Kinases metabolism, Serine metabolism, Signal Transduction, Vero Cells, Virulence, Virulence Factors metabolism, Virus Replication, Orthohantavirus metabolism, Interferon-beta metabolism, Nucleocapsid Proteins metabolism
- Abstract
Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS) and is the only hantavirus shown to spread person to person and cause a highly lethal HPS-like disease in Syrian hamsters. The unique ability of ANDV N protein to inhibit beta interferon (IFNβ) induction may contribute to its virulence and spread. Here we analyzed IFNβ regulation by ANDV N protein substituted with divergent residues from the nearly identical Maporal virus (MAPV) N protein. We found that MAPV N fails to inhibit IFNβ signaling and that replacing ANDV residues 252 to 296 with a hypervariable domain (HVD) from MAPV N prevents IFNβ regulation. In addition, changing ANDV residue S386 to the histidine present in MAPV N or the alanine present in other hantaviruses prevented ANDV N from regulating IFNβ induction. In contrast, replacing serine with phosphoserine-mimetic aspartic acid (S386D) in ANDV N robustly inhibited interferon regulatory factor 3 (IRF3) phosphorylation and IFNβ induction. Additionally, the MAPV N protein gained the ability to inhibit IRF3 phosphorylation and IFNβ induction when ANDV HVD and H386D replaced MAPV residues. Mass spectroscopy analysis of N protein from ANDV-infected cells revealed that S386 is phosphorylated, newly classifying ANDV N as a phosphoprotein and phosphorylated S386 as a unique determinant of IFN regulation. In this context, the finding that the ANDV HVD is required for IFN regulation by S386 but dispensable for IFN regulation by D386 suggests a role for HVD in kinase recruitment and S386 phosphorylation. These findings delineate elements within the ANDV N protein that can be targeted to attenuate ANDV and suggest targeting cellular kinases as potential ANDV therapeutics. IMPORTANCE ANDV contains virulence determinants that uniquely permit it to spread person to person and cause highly lethal HPS in immunocompetent hamsters. We discovered that ANDV S386 and an ANDV-specific hypervariable domain permit ANDV N to inhibit IFN induction and that IFN regulation is directed by phosphomimetic S386D substitutions in ANDV N. In addition, MAPV N proteins containing D386 and ANDV HVD gained the ability to inhibit IFN induction. Validating these findings, mass spectroscopy analysis revealed that S386 of ANDV N protein is uniquely phosphorylated during ANDV infection. Collectively, these findings reveal new paradigms for ANDV N protein as a phosphoprotein and IFN pathway regulator and suggest new mechanisms for hantavirus regulation of cellular kinases and signaling pathways. Our findings define novel IFN-regulating virulence determinants of ANDV, identify residues that can be modified to attenuate ANDV for vaccine development, and suggest the potential for kinase inhibitors to therapeutically restrict ANDV replication., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
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11. A Recurrent Silent Mutation Implicates fecA in Ethanol Tolerance by Escherichia coli.
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Lupino KM, Romano KA, Simons MJ, Gregg JT, Panepinto L, Cruz GM, Grajek L, Caputo GA, Hickman MJ, and Hecht GB
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- Bacterial Proteins genetics, Bacterial Proteins metabolism, Cell Membrane, Cell Membrane Permeability drug effects, Escherichia coli Proteins metabolism, Gene Expression Regulation, Bacterial, Genetic Loci, Membrane Proteins genetics, Membrane Proteins metabolism, Microbial Sensitivity Tests, Microbial Viability drug effects, Silent Mutation, Temperature, Whole Genome Sequencing, Drug Tolerance genetics, Escherichia coli genetics, Escherichia coli metabolism, Escherichia coli Proteins genetics, Ethanol toxicity, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism
- Abstract
Background: An issue associated with efficient bioethanol production is the fact that the desired product is toxic to the biocatalyst. Among other effects, ethanol has previously been found to influence the membrane of E. coli in a dose-dependent manner and induce changes in the lipid composition of the plasma membrane. We describe here the characterization of a collection of ethanol-tolerant strains derived from the ethanologenic Escherichia coli strain FBR5., Results: Membrane permeability assays indicate that many of the strains in the collection have alterations in membrane permeability and/or responsiveness of the membrane to environmental changes such as temperature shifts or ethanol exposure. However, analysis of the strains by gas chromatography and mass spectrometry revealed no qualitative changes in the acyl chain composition of membrane lipids in response to ethanol or temperature. To determine whether these strains contain any mutations that might contribute to ethanol tolerance or changes in membrane permeability, we sequenced the entire genome of each strain. Unexpectedly, none of the strains displayed mutations in genes known to control membrane lipid synthesis, and a few strains carried no mutations at all. Interestingly, we found that four independently-isolated strains acquired an identical C → A (V244 V) silent mutation in the ferric citrate transporter gene fecA. Further, we demonstrated that either a deletion of fecA or over-expression of fecA can confer increased ethanol survival, suggesting that any misregulation of fecA expression affects the cellular response to ethanol., Conclusions: The fact that no mutations were observed in several ethanol-tolerant strains suggested that epigenetic mechanisms play a role in E. coli ethanol tolerance and membrane permeability. Our data also represent the first direct phenotypic evidence that the fecA gene plays a role in ethanol tolerance. We propose that the recurring silent mutation may exert an effect on phenotype by altering RNA-mediated regulation of fecA expression.
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- 2018
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12. Acute Wound Complications After Total Knee Arthroplasty: Prevention and Management.
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Simons MJ, Amin NH, and Scuderi GR
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- Algorithms, Drainage, Humans, Necrosis prevention & control, Necrosis therapy, Postoperative Complications prevention & control, Risk Factors, Arthroplasty, Replacement, Knee adverse effects, Postoperative Complications therapy, Wound Healing
- Abstract
Normal wound healing with avoidance of early wound complications is critical to the success of total knee arthroplasty. The severity of acute complications includes less morbid problems, such as quickly resolved drainage and small superficial eschars, to persistent drainage and full-thickness tissue necrosis, which may require advanced soft-tissue coverage. To achieve proper healing, surgeons must respond to persistent drainage by addressing modifiable patient risk factors, using meticulous surgical technique, and implementing an algorithmic approach to treatment.
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- 2017
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13. Assortative mating for human height: A meta-analysis.
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Stulp G, Simons MJ, Grasman S, and Pollet TV
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- Female, Humans, Male, Body Height, Reproductive Behavior
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Objectives: The study of assortative mating for height has a rich history in human biology. Although the positive correlation between the stature of spouses has often been noted in western populations, recent papers suggest that mating patterns for stature are not universal. The objective of this paper was to review the published evidence to examine the strength of and universality in assortative mating for height., Methods: We conducted an extensive literature review and meta-analysis. We started with published reviews but also searched through secondary databases. Our search led to 154 correlations of height between partners. We classified the populations as western and non-western based on geography. These correlations were then analyzed via meta-analytic techniques., Results: 148 of the correlations for partner heights were positive and the overall analysis indicates moderate positive assortative mating (r = .23). Although assortative mating was slightly stronger in countries that can be described as western compared to non-western, this difference was not statistically significant. We found no evidence for a change in assortative mating for height over time. There was substantial residual heterogeneity in effect sizes and this heterogeneity was most pronounced in western countries., Conclusions: Positive assortative mating for height exists in human populations, but is modest in magnitude suggesting that height is not a major factor in mate choice. Future research is necessary to understand the underlying causes of the large amount of heterogeneity observed in the degree of assortative mating across human populations, which may stem from a combination of methodological and ecological differences., (© 2016 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.)
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- 2017
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14. The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA.
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Gorbunova EE, Simons MJ, Gavrilovskaya IN, and Mackow ER
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- Endothelial Cells physiology, Endothelial Cells virology, Orthohantavirus physiology, Host-Pathogen Interactions, Nucleocapsid Proteins metabolism, Permeability, rhoA GTP-Binding Protein metabolism
- Abstract
Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases. Expression of ANDV N in MECs increased cell size by preventing tuberous sclerosis complex (TSC) repression of Rheb-mTOR-pS6K. N selectively bound the TSC2 N terminus (1 to 1403) within a complex containing TSC2/TSC1/TBC1D7, and endogenous TSC2 reciprocally coprecipitated N protein from ANDV-infected MECs. TSCs normally restrict RhoA-induced MEC permeability, and we found that ANDV infection or N protein expression constitutively activated RhoA. This suggests that the ANDV N protein alone is sufficient to activate signaling pathways that control MEC size and permeability. Further, RhoA small interfering RNA, dominant-negative RhoA(N19), and the RhoA/Rho kinase inhibitors fasudil and Y27632 dramatically reduced the permeability of ANDV-infected MECs by 80 to 90%. Fasudil also reduced the bradykinin-directed permeability of ANDV and Hantaan virus-infected MECs to control levels. These findings demonstrate that ANDV activation of RhoA causes MEC permeability and reveal a potential edemagenic mechanism for ANDV to constitutively inhibit the basal barrier integrity of infected MECs. The central importance of RhoA activation in MEC permeability further suggests therapeutically targeting RhoA, TSCs, and Rac1 as potential means of resolving capillary leakage during hantavirus infections., Importance: HPS is hallmarked by acute pulmonary edema, hypoxia, respiratory distress, and the ubiquitous infection of pulmonary MECs that occurs without disrupting the endothelium. Mechanisms of MEC permeability and targets for resolving lethal pulmonary edema during HPS remain enigmatic. Our findings suggest a novel underlying mechanism of MEC dysfunction resulting from ANDV activation of the Rheb and RhoA GTPases that, respectively, control MEC size and permeability. Our studies show that inhibition of RhoA blocks ANDV-directed permeability and implicate RhoA as a potential therapeutic target for restoring capillary barrier function to the ANDV-infected endothelium. Since RhoA activation forms a downstream nexus for factors that cause capillary leakage, blocking RhoA activation is liable to restore basal capillary integrity and prevent edema amplified by tissue hypoxia and respiratory distress. Targeting the endothelium has the potential to resolve disease during symptomatic stages, when replication inhibitors lack efficacy, and to be broadly applicable to other hemorrhagic and edematous viral diseases., (Copyright © 2016 Gorbunova et al.)
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- 2016
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15. Comparative idiosyncrasies in life extension by reduced mTOR signalling and its distinctiveness from dietary restriction.
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Garratt M, Nakagawa S, and Simons MJ
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- Animals, Drosophila physiology, Female, Mice, Species Specificity, Survival Analysis, Caloric Restriction, Longevity physiology, Signal Transduction, TOR Serine-Threonine Kinases metabolism
- Abstract
Reduced mechanistic target of rapamycin (mTOR) signalling extends lifespan in yeast, nematodes, fruit flies and mice, highlighting a physiological pathway that could modulate aging in evolutionarily divergent organisms. This signalling system is also hypothesized to play a central role in lifespan extension via dietary restriction. By collating data from 48 available published studies examining lifespan with reduced mTOR signalling, we show that reduced mTOR signalling provides similar increases in median lifespan across species, with genetic mTOR manipulations consistently providing greater life extension than pharmacological treatment with rapamycin. In contrast to the consistency in changes in median lifespan, however, the demographic causes for life extension are highly species specific. Reduced mTOR signalling extends lifespan in nematodes by strongly reducing the degree to which mortality rates increase with age (aging rate). By contrast, life extension in mice and yeast occurs largely by pushing back the onset of aging, but not altering the shape of the mortality curve once aging starts. Importantly, in mice, the altered pattern of mortality induced by reduced mTOR signalling is different to that induced by dietary restriction, which reduces the rate of aging. Effects of mTOR signalling were also sex dependent, but only within mice, and not within flies, thus again species specific. An alleviation of age-associated mortality is not a shared feature of reduced mTOR signalling across model organisms and does not replicate the established age-related survival benefits of dietary restriction., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
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- 2016
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16. Stabilizing survival selection on presenescent expression of a sexual ornament followed by a terminal decline.
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Simons MJ, Briga M, and Verhulst S
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- Animals, Beak, Selection, Genetic, Mating Preference, Animal, Pigmentation, Sexual Behavior, Songbirds anatomy & histology, Songbirds genetics
- Abstract
Senescence is a decrease in functional capacity, increasing mortality rate with age. Sexual signals indicate functional capacity, because costs of ornamentation ensure signal honesty, and are therefore expected to senesce, tracking physiological deterioration and mortality. For sexual traits, mixed associations with age and positive associations with life expectancy have been reported. However, whether these associations are caused by selective disappearance and/or within-individual senescence of sexual signals, respectively, is not known. We previously reported that zebra finches with redder bills had greater life expectancy, based on a single bill colour measurement per individual. We here extend this analysis using longitudinal data and show that this finding is attributable to terminal declines in bill redness in the year before death, with no detectable change in presenescent redness. Additionally, there was a quadratic relationship between presenescent bill colouration and survival: individuals with intermediate bill redness have maximum survival prospects. This may reflect that redder individuals overinvest in colouration and/or associated physiological changes, while below-average bill redness probably reflects poorer phenotypic quality. Together, this pattern suggests that bill colouration is defended against physiological deterioration, because of mate attraction benefits, or that physiological deterioration is not a gradual process, but accelerates sharply prior to death. We discuss these possibilities in the context of the reliability theory of ageing and sexual selection., (© 2016 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)
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- 2016
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17. Characterization of the Neural Anatomy in the Hip Joint to Optimize Periarticular Regional Anesthesia in Total Hip Arthroplasty.
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Simons MJ, Amin NH, Cushner FD, and Scuderi GR
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- Hip Joint surgery, Humans, Anesthesia, Conduction methods, Arthroplasty, Replacement, Hip, Hip Joint innervation, Lumbosacral Plexus anatomy & histology
- Abstract
The purpose of the current study was to identify and map the periarticular neural anatomy of the hip to optimize periarticular injection techniques in total hip arthroplasty. A literature review of common search engines was performed using terms associated with hip innervation and 17 met the inclusion criteria. The studies addressed both gross and microscopic neural anatomy of the human hip joint, and the findings summarize key areas of hip mechanoreceptors and free nerve endings to provide a framework for targeted periarticular hip infiltration. Grossly, the hip joint is supplied by the femoral, obturator, sciatic, and superior gluteal nerves, as well as the nerve to the quadratus femoris. The greatest concentration of sensory nerve endings and mechanoreceptors is found at the anterior hip capsule, especially superiorly. The labrum is most highly innervated from the 10 to 2 o'clock position. After the cup and liner are placed, periarticular injections should be infiltrated toward the remnant labrum from 10 to 2 o'clock. Before stem insertion, the visible periosteum may then be injected circumferentially about the femur. The anterior and superior capsular tissue, if retained, is routinely infiltrated at the time of capsular repair. Depending on surgical approach, the fascia and incised soft tissue are infiltrated before final closure.
- Published
- 2015
18. Oxidative stress and life histories: unresolved issues and current needs.
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Speakman JR, Blount JD, Bronikowski AM, Buffenstein R, Isaksson C, Kirkwood TB, Monaghan P, Ozanne SE, Beaulieu M, Briga M, Carr SK, Christensen LL, Cochemé HM, Cram DL, Dantzer B, Harper JM, Jurk D, King A, Noguera JC, Salin K, Sild E, Simons MJ, Smith S, Stier A, Tobler M, Vitikainen E, Peaker M, and Selman C
- Abstract
Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other.
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- 2015
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19. Questioning causal involvement of telomeres in aging.
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Simons MJ
- Subjects
- Causality, Epidemiologic Measurements, Humans, Aging genetics, Telomere Homeostasis physiology, Telomere Shortening physiology
- Abstract
Multiple studies have demonstrated that telomere length predicts mortality and that telomeres shorten with age. Although rarely acknowledged these associations do not dictate causality. I review telomerase knockout and overexpression studies and find little support that telomeres cause aging. In addition, the causality hypothesis assumes that there is a critical telomere length at which senescence is induced. This generates the prediction that variance in telomere length decreases with age. In contrast, using meta-analysis of human data, I find no such decline. Inferring the causal involvement of telomeres in aging from current knowledge is therefore speculative and could hinder scientific progress., (Copyright © 2015 The Author. Published by Elsevier B.V. All rights reserved.)
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- 2015
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20. Commentary: The reliability of telomere length measurements.
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Verhulst S, Susser E, Factor-Litvak PR, Simons MJ, Benetos A, Steenstrup T, Kark JD, and Aviv A
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- Humans, Reproducibility of Results, Telomere
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- 2015
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21. Limited catching bias in a wild population of birds with near-complete census information.
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Simons MJ, Winney I, Nakagawa S, Burke T, and Schroeder J
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Animal research often relies on catching wild animals; however, individuals may have different trappability, and this can generate bias. We studied bias in mist netting, the main method for catching wild birds. The unusually high resighting rate in our study population-house sparrows (Passer domesticus) on Lundy Island (England)-allowed us to obtain accurate estimates of the population size. This unique situation enabled us to test for catching bias in mist netting using deviations from the expected Poisson distribution. There was no evidence that a fraction of the birds in the population consistently remained uncaught. However, we detected a different bias: More birds than expected were captured only once within a year. This bias probably resulted from a mixture of fieldworkers sometimes ignoring rapid recaptures and birds becoming net shy after their first capture. We had sufficient statistical power with the available data to detect a substantial uncaught fraction. Therefore, our data are probably unbiased toward catching specific individuals from our population. Our analyses demonstrate that intensively monitored natural insular populations, in which population size can be estimated precisely, provide the potential to address important unanswered questions without concerns about a fraction of the population remaining uncaught. Our approach can help researchers to test for catching bias in closely monitored wild populations for which reliable estimates of population size and dispersal are available.
- Published
- 2015
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22. An appraisal of how the vitamin A-redox hypothesis can maintain honesty of carotenoid-dependent signals.
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Simons MJ, Groothuis TG, and Verhulst S
- Abstract
The vitamin A-redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid-dependent traits. A key aspect of the vitamin A-redox hypothesis, applicable to both yellow and red coloration, is the hypothesized negative feedback of tightly regulated Vitamin A plasma levels on the enzyme responsible for sequestering both Vitamin A and carotenoids from the gut. We performed a meta-analysis and find that vitamin A levels are positively related to carotenoid plasma levels (r = 0.50, P = 0.0002). On the basis of this finding and further theoretical considerations, we propose that the vitamin A-redox hypothesis is unlikely to explain carotenoid-dependent honest signaling.
- Published
- 2015
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23. Carotenoid-dependent signals and the evolution of plasma carotenoid levels in birds.
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Simons MJ, Maia R, Leenknegt B, and Verhulst S
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- Animals, Antioxidants metabolism, Biological Evolution, Birds metabolism, Carotenoids metabolism, Phylogeny, Signal Transduction, Birds physiology, Carotenoids blood, Pigmentation physiology, Sex Characteristics
- Abstract
Sexual selection has resulted in a wide array of ornaments used in mate choice, and such indicator traits signal quality honestly when they bear costs, precluding cheating. Carotenoid-dependent coloration has attracted considerable attention in this context, because investing carotenoids in coloration has to be traded off against its physiological functions; carotenoids are antioxidants and increase immunocompetence. This trade-off is hypothesized to underlie the honesty of carotenoid-dependent coloration, signaling the "handicap" of allocating carotenoids away from somatic maintenance toward sexual display. Utilizing recent advances in modeling adaptive evolution, we used a comparative approach to investigate the evolution of plasma carotenoid levels using a species-level phylogeny of 178 bird species. We find that the evolutionary optimum for carotenoid levels is higher in lineages that evolved carotenoid-dependent coloration, with strong attraction toward this optimum. Hence, carotenoids do not appear to be limiting, given that higher carotenoid levels readily evolve in response to the evolution of carotenoid-dependent coloration. These findings challenge the assumption that carotenoids are a scarce resource and thus also challenge the hypothesis that physiological resource value of carotenoids underlies honesty of carotenoid-dependent traits. Therefore, the comparative evidence suggests that other factors, such as the acquisition and incorporation of carotenoids, are involved in maintaining signal honesty.
- Published
- 2014
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24. The biological clock modulates the human cortisol response in a multiplicative fashion.
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van de Werken M, Booij SH, van der Zwan JE, Simons MJ, Gordijn MC, and Beersma DG
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- Activity Cycles, Biomarkers metabolism, Humans, Male, Melatonin metabolism, Photoperiod, Saliva metabolism, Sleep, Sleep Disorders, Circadian Rhythm metabolism, Sleep Disorders, Circadian Rhythm physiopathology, Stress, Physiological, Time Factors, Wakefulness, Young Adult, Biological Clocks, Circadian Rhythm, Hydrocortisone metabolism
- Abstract
Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol response is modulated by circadian phase. Exposure to stress at an unnatural phase, as in shift work, is predicted to result in abnormal cortisol levels. Health of shift workers may therefore improve when stress is reduced at times when the clock produces high stress sensitivity.
- Published
- 2014
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25. Temporal niche switching and reduced nest attendance in response to heat dissipation limits in lactating common voles (Microtus arvalis).
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van der Vinne V, Simons MJ, Reimert I, and Gerkema MP
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- Animals, Arvicolinae physiology, Behavior, Animal physiology, Circadian Rhythm physiology, Female, Hot Temperature, Lactation physiology, Male, Pregnancy, Time Factors, Arvicolinae psychology, Body Temperature Regulation physiology, Lactation psychology, Nesting Behavior physiology
- Abstract
According to the heat dissipation limit theory, maximum metabolic turnover is limited by the capacity of the body to dissipate excess heat. Small mammals, including common voles (Microtus arvalis), face a heat dissipation limitation during lactation. Pup growth and milk production are reduced under higher ambient temperatures. Heat dissipation problems might in part be alleviated by modifying behavior, such as reducing nest attendance and being active at energetically optimal times of day. According to the circadian thermo-energetics hypothesis, animals can make use of daily ambient temperature fluctuations to alter their energetic expenditure. In this study we test whether heat challenged (housing at 30 °C compared to 21 °C) lactating common voles allocate their time differently among behaviors and whether their ultradian and circadian behavioral rhythmicity are altered. Behavior was scored every 13 min from automated picture recordings, while general locomotor activity was measured by passive infrared detectors to assess ultradian and circadian organization. The effects of ambient temperature on the ultradian organization of behavior were assessed by determining the ultradian period length and the distribution of activity within the ultradian bout. Changes in circadian organization were assessed by the distribution of activity over the light and dark phase. As a complementary measure nest temperature recordings were used to quantify nest attendance distribution between day and night. Lactating dams at 30 °C reduced the fraction of time spent on the nest while increasing the fraction of time resting without pups away from the nest. The ultradian period of locomotor activity was longer in voles housed at 30 °C during pregnancy and lactation, but not after weaning when the pups were removed. No differences in the distribution of activity within the ultradian bout could be detected. The circadian organization was also modulated by ambient temperature. Lactating voles housed at 30 °C became more day active and a loss of day-night differences in nest temperature suggests a shift of nest attendance towards the night. Reducing the time attending the nest can reduce the risk of hyperthermia, and may be the behavioral component resulting in lower milk production and hence reproductive output. Becoming more day active allows feeding and nursing of the pups during the rest phase to occur during the night at which lower ambient temperatures are expected in the field. In natural situations this strategy will increase heat dissipation and lactation capacity. Whether there are similar benefits associated with a longer ultradian period is currently unknown, but these are likely to result from decreased energy turnover at 30 °C. In conclusion, our study shows that lactating common voles facing heat dissipation problems re-organize their behavior in a way that can maximize heat dissipation capabilities and thereby optimize lactation capacity., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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26. A statistical approach to distinguish telomere elongation from error in longitudinal datasets.
- Author
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Simons MJ, Stulp G, and Nakagawa S
- Subjects
- Bias, Humans, Aging physiology, Data Interpretation, Statistical, Databases, Factual statistics & numerical data, Telomere ultrastructure, Telomere Homeostasis physiology
- Abstract
Telomere length and the rate of telomere attrition vary between individuals and have been interpreted as the rate at which individuals have aged. The biology of telomeres dictates shortening with age, although telomere elongation with age has repeatedly been observed within a minority of individuals in several populations. These findings have been attributed to error, rather than actual telomere elongation, restricting our understanding of its possible biological significance. Here we present a method to distinguish between error and telomere elongation in longitudinal datasets, which is easy to apply and has few assumptions. Using simulations, we show that the method has considerable statistical power (>80 %) to detect even a small proportion (6.7 %) of TL increases in the population, within a relatively small sample (N = 200), while maintaining the standard level of Type I error rate (α ≤ 0.05).
- Published
- 2014
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27. Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.
- Author
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Simons MJ, Koch W, and Verhulst S
- Subjects
- Animals, Diet, Eating, Life Expectancy, Mice, Rats, Survival Rate, Aging physiology, Caloric Restriction mortality, Longevity
- Abstract
Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz-Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)
- Published
- 2013
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28. Telomere length behaves as biomarker of somatic redundancy rather than biological age.
- Author
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Boonekamp JJ, Simons MJ, Hemerik L, and Verhulst S
- Subjects
- Aged, Aged, 80 and over, Biomarkers analysis, Blood Pressure, Body Mass Index, Cholesterol blood, Computer Simulation, Humans, Leukocytes chemistry, Middle Aged, Life Expectancy, Longevity, Models, Statistical, Telomere chemistry, Telomere Homeostasis
- Abstract
Biomarkers of aging are essential to predict mortality and aging-related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging because their associations with mortality generally diminish with age. How this pattern arises is, however, not understood. With meta-analysis we show that human leucocyte telomere length (TL) predicts mortality, and that this mortality association diminishes with age, as found for other biomarkers of aging. Subsequently, we demonstrate with simulation models that this observation cannot be reconciled with the popular hypothesis that TL is proportional to biological age. Using the reliability theory of aging, we instead propose that TL is a biomarker of somatic redundancy, the body's capacity to absorb damage, which fits the observed pattern well. We discuss to what extent diminishing redundancy with age may also explain the observed diminishing mortality modulation with age of other biomarkers of aging. Considering diminishing somatic redundancy as the causal agent of aging may critically advance our understanding of the aging process, and improve predictions of life expectancy and vulnerability to aging-related diseases., (© 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)
- Published
- 2013
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29. Bill redness is positively associated with reproduction and survival in male and female zebra finches.
- Author
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Simons MJ, Briga M, Koetsier E, Folkertsma R, Wubs MD, Dijkstra C, and Verhulst S
- Subjects
- Animals, Female, Male, Models, Biological, Proportional Hazards Models, Survival Analysis, Beak physiology, Finches physiology, Pigmentation physiology, Reproduction physiology
- Abstract
Sexual traits can serve as honest indicators of phenotypic quality when they are costly. Brightly coloured yellow to red traits, which are pigmented by carotenoids, are relatively common in birds, and feature in sexual selection. Carotenoids have been linked to immune and antioxidant function, and the trade-off between ornamentation and these physiological functions provides a potential mechanism rendering carotenoid based signals costly. Mutual ornamentation is also common in birds and can be maintained by mutual mate choice for this ornament or by a correlated response in one sex to selection on the other sex. When selection pressures differ between the sexes this can cause intralocus sexual conflict. Sexually antagonistic selection pressures have been demonstrated for few sexual traits, and for carotenoid-dependent traits there is a single example: bill redness was found to be positively associated with survival and reproductive output in male zebra finches, but negatively so in females. We retested these associations in our captive zebra finch population without two possible limitations of this earlier study. Contrary to the earlier findings, we found no evidence for sexually antagonistic selection. In both sexes, individuals with redder bills showed higher survival. This association disappeared among the females with the reddest bills. Furthermore, females with redder bills achieved higher reproductive output. We conclude that bill redness of male and female zebra finches honestly signals phenotypic quality, and discuss the possible causes of the differences between our results and earlier findings.
- Published
- 2012
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30. What does carotenoid-dependent coloration tell? Plasma carotenoid level signals immunocompetence and oxidative stress state in birds-A meta-analysis.
- Author
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Simons MJ, Cohen AA, and Verhulst S
- Subjects
- Animals, Color, Immune System, Immunity immunology, Models, Biological, Phylogeny, Signal Transduction, Birds immunology, Birds physiology, Carotenoids chemistry, Immunocompetence immunology, Oxidative Stress, Pigmentation immunology
- Abstract
Mechanisms maintaining honesty of sexual signals are far from resolved, limiting our understanding of sexual selection and potential important parts of physiology. Carotenoid pigmented visual signals are among the most extensively studied sexual displays, but evidence regarding hypotheses on how carotenoids ensure signal honesty is mixed. Using a phylogenetically controlled meta-analysis of 357 effect sizes across 88 different species of birds, we tested two prominent hypotheses in the field: that carotenoid-dependent coloration signals i) immunocompetence and/or ii) oxidative stress state. Separate meta-analyses were performed for the relationships of trait coloration and circulating carotenoid level with different measures of immunocompetence and oxidative stress state. For immunocompetence we find that carotenoid levels (r = 0.20) and trait color intensity (r = 0.17) are significantly positively related to PHA response. Additionally we find that carotenoids are significantly positively related to antioxidant capacity (r = 0.10), but not significantly related to oxidative damage (r = -0.02). Thus our analyses provide support for both hypotheses, in that at least for some aspects of immunity and oxidative stress state the predicted correlations were found. Furthermore, we tested for differences in effect size between experimental and observational studies; a larger effect in observational studies would indicate that co-variation might not be causal. However, we detected no significant difference, suggesting that the relationships we found are causal. The overall effect sizes we report are modest and we discuss potential factors contributing to this, including differences between species. We suggest complementary mechanisms maintaining honesty rather than the involvement of carotenoids in immune function and oxidative stress and suggest experiments on how to test these.
- Published
- 2012
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31. Nasopharyngeal carcinoma as a paradigm of cancer genetics.
- Author
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Simons MJ
- Subjects
- China epidemiology, Herpesvirus 4, Human immunology, Humans, Nasopharyngeal Neoplasms ethnology, Nasopharyngeal Neoplasms immunology, Emigration and Immigration, Genetics, Population, Nasopharyngeal Neoplasms genetics
- Abstract
The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modern day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome combinations, or haplotypes (e.g. HLA-A2-B46), whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently, a strength of association reflecting the 30-50-fold difference in incidence between highest risk Cantonese and lowest-risk Indians. The prototypic haplotype HLA-A2-B46 extends over megabases. An upstream DNA segment (near HLA-DPA1), has close similarity to Gorilla, with no obvious homology to Chimpanzee in current databases, suggesting that a reticulate model of primate evolution may be more appropriate than simple phylogeny. The DNA variation level in this segment is high enough for it to be a hominin remnant. HLA-B46 arose in mongoloids and remains largely limited to Chinese so the question arises as to whether the hominin candidate segment indicates an eastward trek of Homo neanderthalensis or the survival of much earlier Homo erectus? In 2011 sequencing technologies have finally caught up with the requirement to separate parental haplotypes. Recently achieved chromosome separation for whole genome di-haploid genetic and epigenetic analysis of parental inheritance in single individuals will reveal interacting patterns of multi-locus haplotypes as humans move in and through successive environments, thus providing definitive information on the genetic affinities between extant populations, and of the migrations that have led to the global distribution of modern Homo. The challenge can now be met of seeking HLA-associated locations both within and outside the HLA complex on each of the pair of chromosomes. More broadly, for every disease, genetic risk detection will require resolution of the diploid genome as a di-haplome. In the context of NPC, HLA genetic risk complete autosomal di-haplomic sequencing will enable testing of the Wee unitary origin hypothesis of NPC risk even among populations with no apparent mongoloid affinity.
- Published
- 2011
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32. Nasopharyngeal carcinoma in the Northeastern states of India.
- Author
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Kataki AC, Simons MJ, Das AK, Sharma K, and Mehra NK
- Subjects
- Asian People genetics, Genetic Predisposition to Disease epidemiology, Humans, Incidence, Nasopharyngeal Neoplasms ethnology, Nasopharyngeal Neoplasms genetics, Sikkim epidemiology, Emigration and Immigration, Genetics, Population, India epidemiology, Nasopharyngeal Neoplasms epidemiology
- Abstract
Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as about 20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.
- Published
- 2011
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33. The prevalence and prevention of nasopharyngeal carcinoma in China.
- Author
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Cao SM, Simons MJ, and Qian CN
- Subjects
- Age Factors, Antibodies, Viral analysis, Antigens, Viral analysis, Asian People genetics, Capsid Proteins analysis, Carcinoma, China epidemiology, Herpesvirus 4, Human immunology, Humans, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms genetics, Nasopharyngeal Neoplasms immunology, Prevalence, Early Detection of Cancer methods, Nasopharyngeal Neoplasms epidemiology, Nasopharyngeal Neoplasms prevention & control
- Abstract
Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti-Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening.
- Published
- 2011
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34. Ambient temperature shapes reproductive output during pregnancy and lactation in the common vole (Microtus arvalis): a test of the heat dissipation limit theory.
- Author
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Simons MJ, Reimert I, van der Vinne V, Hambly C, Vaanholt LM, Speakman JR, and Gerkema MP
- Subjects
- Animals, Cross-Over Studies, Energy Metabolism physiology, Female, Likelihood Functions, Litter Size, Milk physiology, Models, Biological, Netherlands, Pregnancy, Survival Analysis, Arvicolinae physiology, Body Temperature Regulation physiology, Fertility physiology, Lactation physiology, Temperature
- Abstract
The heat dissipation limit theory suggests that heat generated during metabolism limits energy intake and, thus, reproductive output. Experiments in laboratory strains of mice and rats, and also domestic livestock generally support this theory. Selection for many generations in the laboratory and in livestock has increased litter size or productivity in these animals. To test the wider validity of the heat dissipation limit theory, we studied common voles (Microtus arvalis), which have small litter sizes by comparison with mice and rats, and regular addition of wild-caught individuals of this species to our laboratory colony ensures a natural genetic background. A crossover design of ambient temperatures (21 and 30°C) during pregnancy and lactation was used. High ambient temperature during lactation decreased milk production, slowing pup growth. The effect on pup growth was amplified when ambient temperature was also high during pregnancy. Shaving fur off dams at 30°C resulted in faster growth of pups; however, no significant increase in food intake and or milk production was detected. With increasing litter size (natural and enlarged), asymptotic food intake during lactation levelled off in the largest litters at both 21 and 30°C. Interestingly, the effects of lactation temperature on pup growth where also observed at smaller litter sizes. This suggests that vole dams trade-off costs associated with hyperthermia during lactation with the yield from investment in pup growth. Moreover, pup survival was higher at 30°C, despite lower growth, probably owing to thermoregulatory benefits. It remains to be seen how the balance is established between the negative effect of high ambient temperature on maternal milk production and pup growth (and/or future reproduction of the dam) and the positive effect of high temperatures on pup survival. This balance ultimately determines the effect of different ambient temperatures on reproductive success.
- Published
- 2011
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35. The origin of genetic risk for nasopharyngeal carcinoma:a commentary on: is nasopharyngeal cancer really a "Cantonese cancer"?
- Author
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Simons MJ
- Subjects
- Female, Humans, Male, Asian People genetics, Ethnicity genetics, Genetics, Population, Nasopharyngeal Neoplasms epidemiology, Nasopharyngeal Neoplasms ethnology
- Published
- 2010
- Full Text
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36. As mass media evolves into "masses of media", what are the implications for our health?
- Author
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Sweet MA and Simons MJ
- Subjects
- Attitude to Health, Health Promotion, Humans, Blogging, Consumer Health Information, Mass Media, Social Marketing
- Published
- 2009
- Full Text
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37. The evolution of the cyanobacterial posttranslational clock from a primitive "phoscillator".
- Author
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Simons MJ
- Subjects
- Adenosine Triphosphate metabolism, Animals, Bacterial Proteins metabolism, Circadian Rhythm Signaling Peptides and Proteins, Cyanobacteria classification, Photoperiod, Phylogeny, Biological Clocks physiology, Circadian Rhythm physiology, Cyanobacteria physiology, Evolution, Molecular
- Abstract
Cyanobacteria were among the 1st organisms to evolve on earth. The molecular circadian clock proteins of cyanobacteria and their phylogenetics have recently been elucidated. This allows for a conjecture on the evolution of 1 of the 1st circadian clocks. A scenario has now been created by combining known in vitro and in vivo properties of the 3 clock proteins of cyanobacteria (KaiA, KaiB, and KaiC). This scenario describes the evolution of the cyanobacterial clock in gradual steps: evolving from a masking mechanism, toward an hourglass, into a clock.
- Published
- 2009
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38. Lego clocks: building a clock from parts.
- Author
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Brunner M, Simons MJ, and Merrow M
- Subjects
- Models, Biological, Phosphorylation, Bacterial Proteins physiology, Biological Clocks, Synechococcus physiology
- Abstract
A new finding opens up speculation that the molecular mechanism of circadian clocks in Synechococcus elongatus is composed of multiple oscillator systems (Kitayama and colleagues, this issue, pp. 1513-1521), as has been described in many eukaryotic clock model systems. However, an alternative intepretation is that the pacemaker mechanism-as previously suggested-lies primarily in the rate of ATP hydrolysis by the clock protein KaiC.
- Published
- 2008
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39. Genomics, morphogenesis and biophysics: triangulation of Purkinje cell development.
- Author
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Simons MJ and Pellionisz AJ
- Subjects
- Animals, Biophysical Phenomena, Cerebellum cytology, Cerebellum growth & development, Humans, Biophysics, Genomics, Morphogenesis, Purkinje Cells physiology
- Abstract
The cerebellar Purkinje cells (P-cells) comprise an organelle that is suitable for combined analysis by morphology and genomics, using biophysical tools. In some unknown way, genomic information specifies the development of P-cells. One of us (AJP) has previously proposed that fractal processes associated with DNA are in a causal relation to the fractal properties of organelles such as P-cells (FractoGene, 2002, patent pending). This fractal postulate predicts that the dendritic arborization of P-cells will be less complex in lower order vertebrates. The prediction can be tested by systematic comparative neuroanatomy of the P-cell in species for which genome sequences permit inter-species comparison. The Fugu rubripes (Fugu), Danio rerio (Danio) and other species are lower order vertebrates for which genome sequences are available and tests could be conducted. Consistent with the fractal prediction, P-cell dendritic arbor is primitive in Fugu, being much less complex than in Mus musculus and in Homo sapiens. Genomic analysis readily identified PEP19/Pcp4, Calbindin-D28k, and GAD67 genes in Fugu and in Danio that are closely associated with P-cells in Canis familiaris, Rattus norvegicus, Mus musculus and Homo sapiens. Gene L7/Pcp2 exhibits strongest association with P-cells in higher vertebrates. L7/Pcp2 shows strong protein residue homology with genes greater than 600 residues and including 2-3 GoLoco domains, designated as having G protein signaling modulator function (AGS3-like proteins). Fugu has a short gene with a single GoLoco domain, but it has greatest homology with the AGS3-like proteins. No similar short gene is present in Danio or in Xenopus. Classical L7/Pcp2 is only detected in higher vertebrates, suggesting that it may be a marker of more recent evolutionary development of cerebellar P-cells. We expect that a new generation of data mining tools will be required to support recursive fractal geometrical, combinatorial, and neural network models of the genomic basis of morphogenesis.
- Published
- 2006
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40. Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors.
- Author
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Becker JA, Mirjolet JF, Bernard J, Burgeon E, Simons MJ, Vassart G, Parmentier M, and Libert F
- Subjects
- Breast Neoplasms genetics, Carcinoma genetics, Cell Division physiology, Female, Gene Expression Regulation, Neoplastic physiology, Humans, Receptor, Bradykinin B2 metabolism, Receptors, G-Protein-Coupled, Receptors, Kisspeptin-1, Transcription, Genetic physiology, Up-Regulation physiology, Apoptosis physiology, Breast Neoplasms metabolism, Carcinoma metabolism, Cell Cycle physiology, Receptors, Neuropeptide metabolism
- Abstract
GPR54 is a receptor for peptides derived from the metastasis suppressor gene KiSS-1. To investigate the intracellular mechanisms involved in the reduction of the metastatic potential of MDA-MB-435S cells expressing GPR54, a time course stimulation by kisspeptin-10 over a period of 25 h was performed using cDNA microarrays. Comparison with the bradykinin B(2) receptor revealed a distinct pattern of gene regulation despite a common coupling to the G(q/11) class of G-proteins. Inhibitors of PLC and PK-C abolished the transcriptional regulation of all tested genes, while an inhibitor of p42/44 affected a subset of genes controlled both by GPR54 and B(2). Among the genes specifically up-regulated by GPR54, we found several proapoptotic genes. Stimulation of GPR54 promoted apoptosis while no significant change was observed after B(2) receptor activation. Our results suggest that the metastasis suppressor properties of GPR54 are mediated in part by cell cycle arrest and induction of apoptosis in malignant cells.
- Published
- 2005
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41. Frequency of the CCR5delta32 allele in the Moroccan population.
- Author
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Elharti E, Elaouad R, Simons MJ, Messouak-Elhachimi Z, Gluckman JC, Parmentier M, and Benjouad A
- Subjects
- Alleles, Female, Humans, Male, Morocco, Gene Frequency, Receptors, CCR5 genetics
- Published
- 2000
- Full Text
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42. Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene.
- Author
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Mollereau C, Simons MJ, Soularue P, Liners F, Vassart G, Meunier JC, and Parmentier M
- Subjects
- Amino Acid Sequence, Animals, Brain physiology, Chromosome Mapping, Chromosomes, Artificial, Yeast, Chromosomes, Human, Pair 8, DNA Primers chemistry, Gene Expression, Genes, Humans, Mice, Molecular Sequence Data, Protein Precursors genetics, RNA, Messenger genetics, Rats, Sequence Homology, Amino Acid, Spinal Cord physiology, Tissue Distribution, Transcription, Genetic, Nociceptin, Opioid Peptides genetics
- Abstract
Nociceptin (orphanin FQ), the newly discovered natural agonist of opioid receptor-like (ORL1) receptor, is a neuropeptide that is endowed with pronociceptive activity in vivo. Nociceptin is derived from a larger precursor, prepronociceptin (PPNOC), whose human, mouse, and rat genes we have now isolated. The PPNOC gene is highly conserved in the three species and displays organizational features that are strikingly similar to those of the genes of preproenkephalin, preprodynorphin, and preproopiomelanocortin, the precursors to endogenous opioid peptides, suggesting the four genes belong to the same family-i.e., have a common evolutionary origin. The PPNOC gene encodes a single copy of nociceptin as well as of other peptides whose sequence is strictly conserved across murine and human species; hence it is likely to be neurophysiologically significant. Northern blot analysis shows that the PPNOC gene is predominantly transcribed in the central nervous system (brain and spinal cord) and, albeit weakly, in the ovary, the sole peripheral organ expressing the gene. By using a radiation hybrid cell line panel, the PPNOC gene was mapped to the short arm of human chromosome 8 (8p21), between sequence-tagged site markers WI-5833 and WI-1172, in close proximity of the locus encoding the neurofilament light chain NEFL. Analysis of yeast artificial chromosome clones belonging to the WC8.4 contig covering the 8p21 region did not allow to detect the presence of the gene on these yeast artificial chromosomes, suggesting a gap in the coverage within this contig.
- Published
- 1996
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43. Ancient, highly polymorphic human major histocompatibility complex DQA1 intron sequences.
- Author
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McGinnis MD, Lebo RV, Quinn DL, and Simons MJ
- Subjects
- Algorithms, Alleles, Animals, Base Sequence, Biological Evolution, Exons, Genetics, Population, Haplotypes, Humans, Macaca mulatta, Molecular Sequence Data, Polymerase Chain Reaction, Racial Groups genetics, Sequence Analysis, DNA, HLA-DQ Antigens genetics, Introns, Major Histocompatibility Complex genetics, Polymorphism, Genetic genetics
- Abstract
A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 69 individuals from wide ethnic backgrounds. In contrast, the most variable coding region spanned by the 247 basepair exon 2 defined 11 allelic variants. Our phylogenetic human intron 1 tree derived by the Bootstrap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1-10, 1989]. Thus 3' DQA1 intron 1 and exon 2 have cosegregated since divergence of the human races. Comparison of human alleles to a Rhesus monkey DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolutionary stability of intron sequences since these two species diverged over 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typing for transplantation, paternity testing, and forensics and to derive more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource.
- Published
- 1994
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44. DPB1 locus PCR-RFLP typing of the fourth Asia-Oceania Histocompatibility Workshop cell panel reveals a novel DPB1 allele.
- Author
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Naughton MJ, Limm TM, Ashdown ML, and Simons MJ
- Subjects
- Base Sequence, HLA-DP beta-Chains, Haplotypes genetics, Histocompatibility Testing, Humans, Introns genetics, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Alleles, HLA-DP Antigens genetics
- Abstract
DPB1 locus typing of the 155 cell 4AOHW panel was performed using a PCR-RFLP method. Ambiguity of allele assignment was resolved by amplification using sequence-specific primers. Of the 150 cells for which typings were achieved, three exhibited unusual restriction enzyme fragment patterns, suggesting the possibility of novel DPB1 alleles. Sequence analysis revealed one allele present in the currently reported 46, one novel allele (4AOHW/107) not present among the 46, and one from a non-human primate which is being investigated. Twenty-six (26) of the 34 10IHW cells have been studied previously by cDNA RFLP, and strong haplotypic associations have been demonstrated between DPA1 and DPB1 locus alleles. It is proposed that exploitation of intron polymorphisms making haplotypes will be an integral part of future DPB1 typing as a "first-pass' stratification process to minimize the requirement for sequence-based methods to definitively assign DPB1 alleles.
- Published
- 1994
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45. HLA-DQA1 allele and suballele typing using noncoding sequence polymorphisms. Application to 4AOHW cell panel typing.
- Author
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Limm TM, Ashdown ML, Naughton MJ, McGinnis MD, and Simons MJ
- Subjects
- Alleles, Base Sequence, Cell Line, Transformed immunology, Deoxyribonucleases, Type II Site-Specific metabolism, HLA-DQ Antigens classification, HLA-DQ alpha-Chains, HLA-DR Antigens, Haplotypes, Humans, Molecular Sequence Data, Polymerase Chain Reaction, Exons genetics, HLA-DQ Antigens genetics, Histocompatibility Testing methods, Introns genetics, Polymorphism, Restriction Fragment Length
- Abstract
HLA-DQA1 typing of the 4AOHW cell panel is presented using a novel strategy that exploits both intron and exon polymorphisms. Intron sequences adjacent to the variable HLA-DQA1 second exon exhibit stable polymorphisms that are specific for locus alleles and certain suballelic DR/DQ haplotypes. A PCR-RFLP method has been developed that is based on amplification of a 780-bp segment extending from intron 1 through exon 2 to intron 2. Stable sequence polymorphisms provide restriction enzyme sites and confer mobility variations detected on polyacrylamide minigel electrophoresis. Direct band comparison of amplified products and restriction fragments with known standards facilitates pattern comparison, obviating the requirement for accurate molecular weight determination. This method, using only two enzymes, identifies a total of 11 allelic and suballelic groups, including all eight DQA1 alleles encoded at the second exon.
- Published
- 1993
- Full Text
- View/download PDF
46. Strategy for definition of DR/DQ haplotypes in the 4AOHW cell panel using noncoding sequence polymorphisms.
- Author
-
Simons MJ, Limm TM, Naughton MJ, Quinn DL, McGinnis MD, and Ashdown ML
- Subjects
- Alleles, HLA-DQ Antigens genetics, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Haplotypes genetics, Humans, HLA-DR Antigens genetics, Histocompatibility Antigens Class II genetics, Histocompatibility Testing methods, Introns genetics, Polymorphism, Restriction Fragment Length
- Abstract
Our previously described intron-based DQA1-typing method provides 11 allelic and suballelic groups, including the eight alleles encoded at the second exon. Concurrent testing for the presence of the DRB3, DRB4, and DRB5 loci and the Rsa I pattern of the DRw52 group simplifies the typing requirements for allele assignment at the highly polymorphic DRB1 locus. The DRB1-allele-shortlisting process relies on known DR/DQ haplotypes. In addition to reducing the testing requirements for definitive DRB1 allele assignment, this strategy allows inference of the DR/DQ haplotype and assists in recognition of novel and/or unusual associations.
- Published
- 1993
- Full Text
- View/download PDF
47. Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.
- Author
-
Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, and Mattei MG
- Subjects
- Chromosome Banding, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 22, Cloning, Molecular, Humans, Receptors, Gastrointestinal Hormone metabolism, Receptors, Vasoactive Intestinal Peptide, Chromosome Mapping, Receptors, Gastrointestinal Hormone genetics, Receptors, Purinergic genetics, Receptors, Serotonin genetics, Vasoactive Intestinal Peptide metabolism
- Abstract
cDNA clones encoding four new receptors of the G-protein-coupled receptor family were obtained by selective amplification and cloning from thyroid cDNA and termed RDC1, RDC4, RDC7, and RDC8. RDC7 and RDC8 have recently been identified as A1 and A2 adenosine receptors, respectively. These cDNAs were utilized for chromosomal in situ hybridization to establish the genomic location of the corresponding genes in man. The results indicate that human RDC1, RDC4, RDC7, and RDC8 are in regions 2q37, 1p34.3-1p36.3, 22q11.2-22q13.1, and 11q11-11q13, respectively.
- Published
- 1991
- Full Text
- View/download PDF
48. Defining DNA diagnostic tests appropriate or standard clinical care.
- Author
-
Lebo RV, Cunningham G, Simons MJ, and Shapiro LJ
- Subjects
- Female, Genetic Counseling, Humans, Pregnancy, DNA genetics, Genetic Testing, Prenatal Diagnosis
- Published
- 1990
49. Serum HLA typing.
- Author
-
Tait BD, Finlay RI, and Simons MJ
- Subjects
- Antibody Specificity, Blood Grouping and Crossmatching, Cytotoxicity Tests, Immunologic, Humans, Lymphocytes immunology, HLA Antigens analysis, Histocompatibility Testing methods
- Abstract
This paper establishes that HLA antigens can be detected in serum by lymphocytotoxicity inhibition. A score system is described which enables the degree of cytotoxicity inhibition to be quantitated. The following HLA antigens have been detected: A1, A2, A3, A11, Aw24, B5, B7, B8, B27, Bw35 and B40. It has not been possible to detect HLA-B12.
- Published
- 1981
- Full Text
- View/download PDF
50. Genetic components in susceptibility to nasopharyngeal carcinoma.
- Author
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Kirk RL, Blake NM, Serjeantson S, Simons MJ, and Chan SH
- Subjects
- Acid Phosphatase genetics, Adolescent, Adult, Age Factors, Aged, Carcinoma blood, Child, China ethnology, Chromosome Mapping, Chromosomes, Human, 6-12 and X, Erythrocytes enzymology, Gene Frequency, Genes, Glucosephosphate Dehydrogenase genetics, Humans, Middle Aged, Nasopharyngeal Neoplasms blood, Phenotype, Risk, Singapore, Carcinoma genetics, Nasopharyngeal Neoplasms genetics
- Abstract
A series of blood samples from more than 200 histologically confirmed Chinese patients with NPC in Singapore were typed for 25 genetically controlled red-cell enzyme and five serum protein systems. A comparable number of patients suspected of having NPC but histologically negative and a series of healthy unrelated Chinese were typed for the same systems. The gene frequencies of NPC patients and controls differed by 4% or more in four of the 11 systems that showed variation; a further system, G6PD deficiency, also showed a significant difference between the two series but was excluded because of possible unreliability of the results from patients. Smaller differences existed in several other systems, including chromosome 6 markers closely linked to HLA. An analysis of differences within dialect groups showed a consistent effect for PGD, but for red-cell acid phosphatase there was a reversal of the difference between patients and controls among the Cantonese. These results need a larger series to confirm their validity. A breakdown of patients into those 30 years of age or older and those under 30 slightly enhanced the differences in gene frequencies. A multivariate analysis, using genetic distance statistics, showed a significant difference between NPC patients and controls, which is evident also when they are compared in the separate dialect groups. The histologically negative patients occupied an intermediate position. The study indicates that etiological factors resulting in clinically and histologically confirmed NPC operate on a genetically distinct subpopulation of Chinese in Singapore.
- Published
- 1978
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