Reproductive performance in female ClockΔ19 mutant mice

2004 ◽  
Vol 16 (8) ◽  
pp. 801 ◽  
Author(s):  
David J. Kennaway ◽  
Michael J. Boden ◽  
Athena Voultsios
Keyword(s):  
Reproductive Performance ◽  
Gene Function ◽  
Clock Gene ◽  
Circadian System ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Control Line ◽  
Cba Mice ◽  
The Impact ◽  
The Relationship

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been well established. The present study evaluated the reproductive performance of mice carrying the ClockΔ19 mutation that were either melatonin deficient (ClockΔ19/Δ19) or had the capacity to synthesise melatonin reinstated (ClockΔ19/Δ19+MEL). The ClockΔ19/Δ19 mice took 2–3 days longer to mate, and to subsequently deliver pups, than their control line. The melatonin-competent mutants had a smaller, but still significant (P < 0.05), delay. The ClockΔ19 mutation resulted in smaller median litter sizes compared with control lines (seven v. eight pups; P < 0.05), whereas melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the ClockΔ19/Δ19 and ClockΔ19/Δ19+MEL lines, respectively, compared with 94–96% for the two control lines. The ClockΔ19/Δ19 mutants became behaviourally arrhythmic in constant darkness but, despite this, seven of seven became pregnant when paired with males after at least 14 days of constant darkness (five of seven within 4 days of pairing). In the ClockΔ19/Δ19+MEL mice, seven of 15 became arrhythmic in constant darkness but still became pregnant. The seven mice that free ran for at least 14 days in constant darkness with a period of 27.1 h also became pregnant. The present study has demonstrated that the ClockΔ19 mutation has significant, but subtle, effects on reproductive performance. The reintroduction of melatonin competency and/or other genes as a result of crosses with CBA mice reduced the impact of the mutation further. It would appear that redundancy in genes in the circadian system allows the reproductive cyclicity to persist in mice, albeit at a suboptimal level.

scholarly journals 241.Reproductive performance in Clock mutant mice

2004 ◽  
Vol 16 (9) ◽  
pp. 241
Author(s):  
D. J. Kennaway ◽  
A. Voultsios ◽  
M. J. Boden
Keyword(s):  
Reproductive Performance ◽  
Clock Gene ◽  
Mutant Mice ◽  
Control Line ◽  
Circadian Gene ◽  
Significant Delay ◽  
Clock Mutant ◽  
Mutant Lines ◽  
The Impact ◽  
The Relationship

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been investigated. This study evaluated the reproductive performance of melatonin deficient and proficient mice carrying a mutation in the core circadian gene, Clock. In natural matings, melatonin deficient Clock mutant mice took 2 to 3 days longer to mate and to subsequently deliver pups than their control line. The melatonin proficient mutants (Clock-MEL) had a smaller, but still significant delay (P < 0.05). The Clock mutation resulted in smaller median litter sizes compared to the control lines (7 v. 8 pups, P < 0.05) while melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the melatonin deficient and proficient Clock mutant lines respectively, compared to 94 to 96% for their control lines. When immature mice were subjected to a standard PMSG/HCG superovulation protocol, Clock-MEL mice had lowered fertility and significantly fewer ovulations than their control line although embryo development appeared to be only slightly affected (Table 1, see PDF file).

“Temporal control of tumor growth in nocturnal mammals: impact of the circadian system”

2020 ◽  
Author(s):  
Paula M. Wagner ◽  
César G. Prucca ◽  
Fabiola N. Velázquez ◽  
Lucas Sosa Alderete ◽  
Beatriz L. Caputto ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Clock Gene ◽  
Drug Efficacy ◽  
Circadian System ◽  
Tumor Formation ◽  
Constant Darkness ◽  
Nerve Sheath Tumor ◽  
Temporal Control ◽  
Dark Cycle ◽  
The Impact

AbstractGlioblastoma multiforme is the most aggressive brain tumor; however, little is known about the impact of the circadian system on the tumor formation, growth and treatment. We investigated day/night differences in tumor growth after injecting A530 glioma cells isolated from malignant peripheral nerve sheath tumor of NPcis (Trp53+/-; Nf1+/-) mice. Tumors generated in the sciatic nerve zone of C57BL/6 mice injected early at night in the light/dark cycle or in constant darkness, showed higher growth rates than in animals injected diurnally. Similar nocturnal increases were observed when injecting B16 melanoma cells or when mice received knocked-down clock gene Bmal1 cells. Moreover, treatment with a low-dose of the proteasome inhibitor Bortezomib (0.5 mg/kg) in tumor-bearing animals, displayed higher efficacy when administered at night. Results suggest the existence of a precise temporal control of tumor growth and of drug efficacy in which the host state and susceptibility are critical.

Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases

2009 ◽  
Vol 89 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Benjamin Turgeon ◽  
Sylvain Meloche
Keyword(s):  
Gene Function ◽  
Gene Mutations ◽  
Mutant Mice ◽  
Human Diseases ◽  
Mouse Development ◽  
Phenotypic Analysis ◽  
Mouse Mutants ◽  
Physiological Processes ◽  
Neonatal Lethality ◽  
The Impact

The mouse represents the model of choice to study the biological function of mammalian genes through mutation of its genome. However, the biggest challenge of mouse geneticists remains the phenotypic analysis of mouse mutants. A survey of mouse mutant databases reveals a surprisingly high number of gene mutations leading to neonatal death. These genetically modified mouse mutants have been instrumental in elucidating gene function and have become important models of congenital human diseases. The main complication when phenotyping mutant mice dying during the neonatal period is the large spectrum of physiological systems whose defects can challenge neonatal survival. Here, we present a comprehensive review of gene mutations leading to neonatal lethality and discuss the impact of these mutations on the major physiological processes critical to mouse newborn survival: parturition, breathing, suckling, and homeostasis. Selected examples of mouse mutants are highlighted to illustrate how the precise identification of the timing and cause of death associated with these physiological processes allows for a more profound understanding of the underlying cellular and molecular defects. This review provides a guide for the analysis of neonatal lethal phenotypes in mutant mice that will be helpful for dissecting out the function of specific genes during mouse development.

scholarly journals Reproductive performance primarily depends on the female genotype in a two-factorial breeding experiment using high-fertility mouse lines

Reproduction ◽  
2017 ◽  
Vol 153 (3) ◽  
pp. 361-368 ◽  
Author(s):  
Martina Langhammer ◽  
Marten Michaelis ◽  
Michaela F Hartmann ◽  
Stefan A Wudy ◽  
Alexander Sobczak ◽  
...  
Keyword(s):  
Mouse Models ◽  
Reproductive Performance ◽  
Serum Testosterone ◽  
High Fertility ◽  
Control Line ◽  
Breeding Experiment ◽  
Mating Period ◽  
Female Genotype ◽  
Males And Females ◽  
The Impact

Mouse models showing an improved fertility phenotype are barely described in the literature. In the present study, we further characterized two outbred mouse models that have been selected for the phenotype ‘high fertility’ for more than 177 generations (fertility lines (FL) 1 and 2). In order to delineate the impact of males and females on fertility parameters, we performed a two-factorial breeding experiment by mating males and females of the three different genotypes (FL1, FL2, unselected control (Ctrl)) in all 9 possible combinations. Reproductive performance, such as number of offspring per litter or total birth weight of the entire pup, mainly depends on the female genotype. Although the reproductive performance of FL1 and FL2 is very similar, their phenotypes differ. FL2 animals of both genders are larger compared to FL1 and control animals. Females of the control line delivered offspring earlier compared to FL1 and FL2 dams. Males of FL1 are the lightest and the only ones who gained weight during the two weeks mating period. To address whether this effect is correlated with differing serum androgen levels, we measured the concentrations of testosterone, dehydroepiandrosterone, 4-androstenedione, androstanediol and dihydrotestosterone in males of all three lines by GC–MS. We measured serum testosterone between 5.0 and 6.4 ng/mL, whereas the concentrations of the other androgens were at least one order of magnitude lower, with no significant differences between the lines. Our data indicate that reproductive outcome largely depends on the genotype of the female in a two-factorial breeding experiment and supports previous findings that the phenotype ‘high fertility’ is warranted by using different physiological strategies.

scholarly journals The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tae Won Kim ◽  
Jong-Hyun Jeong ◽  
Seung-Chul Hong
Keyword(s):  
Clock Gene ◽  
Clock Genes ◽  
Circadian System ◽  
Lipid Homeostasis ◽  
Dark Cycle ◽  
Hormonal Imbalance ◽  
Glucose And Lipid Homeostasis ◽  
Highly Correlated ◽  
The Impact ◽  
Insulin Insensitivity

The levels of several hormones fluctuate according to the light and dark cycle and are also affected by sleep, feeding, and general behavior. The regulation and metabolism of several hormones are influenced by interactions between the effects of sleep and the intrinsic circadian system; growth hormone, melatonin, cortisol, leptin, and ghrelin levels are highly correlated with sleep and circadian rhythmicity. There are also endogenous circadian mechanisms that serve to regulate glucose metabolism and similar rhythms pertaining to lipid metabolism, regulated through the actions of various clock genes. Sleep disturbance, which negatively impacts hormonal rhythms and metabolism, is also associated with obesity, insulin insensitivity, diabetes, hormonal imbalance, and appetite dysregulation. Circadian disruption, typically induced by shift work, may negatively impact health due to impaired glucose and lipid homeostasis, reversed melatonin and cortisol rhythms, and loss of clock gene rhythmicity.

Accent Policy and Accent Modification Enterprises as Potential Indicators of Intercultural Power Relations: A Call for an Updated Research Agenda

2013 ◽  
Vol 3 (1) ◽  
pp. 22-33 ◽  
Author(s):  
Brynne D. Ovalle ◽  
Rahul Chakraborty
Keyword(s):  
International Relations ◽  
Identity Construction ◽  
Social Theory ◽  
Power Relations ◽  
Linguistic Diversity ◽  
Cultural Organization ◽  
Using Data ◽  
The Individual ◽  
The Impact ◽  
The Relationship

This article has two purposes: (a) to examine the relationship between intercultural power relations and the widespread practice of accent discrimination and (b) to underscore the ramifications of accent discrimination both for the individual and for global society as a whole. First, authors review social theory regarding language and group identity construction, and then go on to integrate more current studies linking accent bias to sociocultural variables. Authors discuss three examples of intercultural accent discrimination in order to illustrate how this link manifests itself in the broader context of international relations (i.e., how accent discrimination is generated in situations of unequal power) and, using a review of current research, assess the consequences of accent discrimination for the individual. Finally, the article highlights the impact that linguistic discrimination is having on linguistic diversity globally, partially using data from the United Nations Educational, Scientific and Cultural Organization (UNESCO) and partially by offering a potential context for interpreting the emergence of practices that seek to reduce or modify speaker accents.

Business: Making Cents of Coding Systems: Billing for Professional Services

2010 ◽  
Vol 20 (1) ◽  
pp. 3-8
Author(s):  
Dee Adams Nikjeh
Keyword(s):  
Professional Services ◽  
Speech Language Pathology ◽  
Coding Systems ◽  
Language Pathology ◽  
Program Funding ◽  
Fee Schedule ◽  
Procedure Codes ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Abstract Administrators and supervisors face daily challenges over issues such as program funding, service fees, correct coding procedures, and the ever-changing healthcare regulations. Receiving equitable reimbursement for speech-language pathology and audiology services necessitates an understanding of federal coding and reimbursement systems. This tutorial provides information pertaining to two major healthcare coding systems and explains the relationship of these systems to clinical documentation, the Medicare Physician Fee Schedule and equitable reimbursement. An explanation of coding edits and coding modifiers is provided for use in those occasional atypical situations when the standard use of procedural coding may not be appropriate. Also included in this tutorial is a brief discussion of the impact that the Medicare Improvements for Patients and Providers Act of 2008 (HR 6331 Medicare Improvements for Patients and Providers Act [MIPPA], 2008) has had on the valuation of speech-language pathology procedure codes.

The Need to Belong and the Relationship Between Loneliness and Health

2014 ◽  
Vol 22 (4) ◽  
pp. 194-201 ◽  
Author(s):  
Freda-Marie Hartung ◽  
Britta Renner
Keyword(s):  
Individual Differences ◽  
Social Isolation ◽  
Social Situation ◽  
First Year ◽  
Health State ◽  
Need To Belong ◽  
First Year University ◽  
Perceived Social Isolation ◽  
The Impact ◽  
The Relationship

Humans are social animals; consequently, a lack of social ties affects individuals’ health negatively. However, the desire to belong differs between individuals, raising the question of whether individual differences in the need to belong moderate the impact of perceived social isolation on health. In the present study, 77 first-year university students rated their loneliness and health every 6 weeks for 18 weeks. Individual differences in the need to belong were found to moderate the relationship between loneliness and current health state. Specifically, lonely students with a high need to belong reported more days of illness than those with a low need to belong. In contrast, the strength of the need to belong had no effect on students who did not feel lonely. Thus, people who have a strong need to belong appear to suffer from loneliness and become ill more often, whereas people with a weak need to belong appear to stand loneliness better and are comparatively healthy. The study implies that social isolation does not impact all individuals identically; instead, the fit between the social situation and an individual’s need appears to be crucial for an individual’s functioning.

Investigating the Relationship Between Self-Esteem and Stigma Among Young Adults With History of Suicide Attempts

Crisis ◽  
2016 ◽  
Vol 37 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Meshan Lehmann ◽  
Matthew R. Hilimire ◽  
Lawrence H. Yang ◽  
Bruce G. Link ◽  
Jordan E. DeVylder
Keyword(s):  
Young Adults ◽  
Suicide Attempts ◽  
Self Esteem ◽  
High Risk Population ◽  
High Functioning ◽  
People With Mental Illness ◽  
History Of ◽  
The Individual ◽  
The Impact ◽  
The Relationship

Abstract. Background: Self-esteem is a major contributor to risk for repeated suicide attempts. Prior research has shown that awareness of stigma is associated with reduced self-esteem among people with mental illness. No prior studies have examined the association between self-esteem and stereotype awareness among individuals with past suicide attempts. Aims: To understand the relationship between stereotype awareness and self-esteem among young adults who have and have not attempted suicide. Method: Computerized surveys were administered to college students (N = 637). Linear regression analyses were used to test associations between self-esteem and stereotype awareness, attempt history, and their interaction. Results: There was a significant stereotype awareness by attempt interaction (β = –.74, p = .006) in the regression analysis. The interaction was explained by a stronger negative association between stereotype awareness and self-esteem among individuals with past suicide attempts (β = –.50, p = .013) compared with those without attempts (β = –.09, p = .037). Conclusion: Stigma is associated with lower self-esteem within this high-functioning sample of young adults with histories of suicide attempts. Alleviating the impact of stigma at the individual (clinical) or community (public health) levels may improve self-esteem among this high-risk population, which could potentially influence subsequent suicide risk.

Assessing the Impact of Suicide Exclusion Periods on Life Insurance

Crisis ◽  
2010 ◽  
Vol 31 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Paul Yip ◽  
David Pitt ◽  
Yan Wang ◽  
Xueyuan Wu ◽  
Ray Watson ◽  
...  
Keyword(s):  
Life Insurance ◽  
Accidental Death ◽  
Insurance Policy ◽  
Death Rates ◽  
Insurance Policies ◽  
Suicidal Death ◽  
Insured Individual ◽  
The Impact ◽  
Insurance Data ◽  
The Relationship

Background: We study the impact of suicide-exclusion periods, common in life insurance policies in Australia, on suicide and accidental death rates for life-insured individuals. If a life-insured individual dies by suicide during the period of suicide exclusion, commonly 13 months, the sum insured is not paid. Aims: We examine whether a suicide-exclusion period affects the timing of suicides. We also analyze whether accidental deaths are more prevalent during the suicide-exclusion period as life-insured individuals disguise their death by suicide. We assess the relationship between the insured sum and suicidal death rates. Methods: Crude and age-standardized rates of suicide, accidental death, and overall death, split by duration since the insured first bought their insurance policy, were computed. Results: There were significantly fewer suicides and no significant spike in the number of accidental deaths in the exclusion period for Australian life insurance data. More suicides, however, were detected for the first 2 years after the exclusion period. Higher insured sums are associated with higher rates of suicide. Conclusions: Adverse selection in Australian life insurance is exacerbated by including a suicide-exclusion period. Extension of the suicide-exclusion period to 3 years may prevent some “insurance-induced” suicides – a rationale for this conclusion is given.

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