Intermittent hypoxia promotes functional neuroprotection from retinal ischemia in untreated first-generation offspring

ABSTRACTEnvironmental stimuli can promote short- or long-lasting changes in phenotype through epigenetics. Under certain circumstances, induced phenotypes can be passed through the germline to subsequent generations, providing a novel mechanistic basis for disease heritability. In the present study, we tested the hypothesis that repetitively exposing parents to a nonharmful epigenetic stimulus can promote disease resilience in offspring. Male and female mice were mated following brief exposures to mild systemic hypoxia every other day for 16 weeks. Electroretinographic determinations of postischemic function in response to transient unilateral retinal ischemia in their 5-month-old F1 progeny revealed significant resilience to injury relative to animals derived from normoxic control parents. Mass spectrometry identified hundreds of differentially expressed proteins between protected and injured retinae; bioinformatic analyses of the pathways and networks these proteins comprise provided specific mechanistic insights into the molecular manifestation of this injury-resilient phenotype. Thus, epigenetics can modify heritability to promote disease resilience.

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Intermittent Hypoxia Promotes Functional Neuroprotection from Retinal Ischemia in Untreated First-Generation Offspring: Proteomic Mechanistic Insights

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.61.11.15 ◽

2020 ◽

Vol 61 (11) ◽

pp. 15

Author(s):

Jarrod C. Harman ◽

Jessie J. Guidry ◽

Jeffrey M. Gidday

Keyword(s):

Intermittent Hypoxia ◽

First Generation ◽

Retinal Ischemia ◽

Generation Offspring

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Intermittent Hypoxia Promotes Functional Neuroprotection from Retinal Ischemia in Untreated First-Generation Offspring

SSRN Electronic Journal ◽

10.2139/ssrn.3528694 ◽

2020 ◽

Author(s):

Jeff Gidday ◽

Jessie J. Guidry ◽

Jarrod C. Harman

Keyword(s):

Intermittent Hypoxia ◽

First Generation ◽

Retinal Ischemia ◽

Generation Offspring

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Myeloid deletion and therapeutic activation of AMP-activated protein kinase (AMPK) do not alter atherosclerosis in male or female mice

10.1101/2020.07.15.204487 ◽

2020 ◽

Author(s):

Nicholas D. LeBlond ◽

Peyman Ghorbani ◽

Conor O’Dwyer ◽

Nia Ambursley ◽

Julia R. C. Nunes ◽

...

Keyword(s):

Protein Kinase ◽

First Generation ◽

Western Diet ◽

Daily Injection ◽

Catalytic Subunits ◽

Male And Female ◽

Ampk Signaling ◽

Female Mice ◽

Amp Activated Protein Kinase ◽

Progression Of Atherosclerosis

AbstractObjectiveThe dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis.Approach and ResultsWe aimed to clarify the role of myeloid-specific AMPK signaling by using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), in male and female mice made acutely atherosclerotic by PCSK9-AAV and Western diet-feeding. After 6 weeks of Western diet feeding, half received daily injection of either the AMPK activator, A-769662 or a vehicle control for a further 6 weeks. After 12 weeks, myeloid cell populations were not different between genotype or sex. Similarly, aortic sinus plaque size, lipid staining and necrotic area were not different in male and female MacKO mice compared to their littermate floxed controls. Moreover, therapeutic intervention with A-769662 had no effect. There were no differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area or markers of autophagy showed no effect of either lacking AMPK signaling or systemic AMPK activation.ConclusionsOur data suggest that while defined roles for each catalytic AMPK subunit have been identified, global deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Moreover, we show that intervention with the first-generation AMPK activator, A-769662, was not able to stem the progression of atherosclerosis.Highlights- The deletion of both catalytic subunits of AMPK in myeloid cells has no significant effect on the progression of atherosclerosis in either male or female mice- Therapeutic delivery of a first-generation AMPK activator (A-769662) for the last 6 weeks of 12-week study had no beneficial effect in either male or female mice- Studying total AMPK deletion may mask specific effects of each isoform and highlights the need for targeted disruption of AMPK phosphorylation sites via knock-in mutations, rather than the traditional “sledgehammer” knockout approach

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Specific Interactions Between Autosome and X Chromosomes Cause Hybrid Male Sterility in Caenorhabditis Species

Genetics ◽

10.1534/genetics.119.302202 ◽

2019 ◽

Vol 212 (3) ◽

pp. 801-813 ◽

Cited By ~ 4

Author(s):

Yu Bi ◽

Xiaoliang Ren ◽

Runsheng Li ◽

Qiutao Ding ◽

Dongying Xie ◽

...

Keyword(s):

Male Sterility ◽

Male Fertility ◽

Genetic Mechanism ◽

Hybrid Male ◽

Female Progeny ◽

Hybrid Male Sterility ◽

Male And Female ◽

F1 Progeny ◽

Asymmetric Hybrid ◽

Parent Of Origin

Hybrid male progeny from interspecies crosses are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often demonstrate parent-of-origin asymmetry. However, the underlying genetic mechanism of asymmetric sterility or inviability remains elusive. We previously established a genome-wide hybrid incompatibility (HI) landscape between Caenorhabditis briggsae and C. nigoni by phenotyping a large collection of C. nigoni strains each carrying a C. briggsae introgression. In this study, we systematically dissect the genetic mechanism of asymmetric sterility and inviability in both hybrid male and female progeny between the two species. Specifically, we performed reciprocal crosses between C. briggsae and different C. nigoni strains that each carry a GFP-labeled C. briggsae genomic fragment referred to as introgression, and scored the HI phenotypes in the F1 progeny. The aggregated introgressions cover 94.6% of the C. briggsae genome, including 100% of the X chromosome. Surprisingly, we observed that two C. briggsaeX fragments that produce C. nigoni male sterility as an introgression rescued hybrid F1 sterility in males fathered by C. briggsae. Subsequent backcrossing analyses indicated that a specific interaction between the X-linked interaction and one autosome introgression is required to rescue the hybrid male sterility. In addition, we identified another two C. briggsae genomic intervals on chromosomes II and IV that can rescue the inviability, but not the sterility, of hybrid F1 males fathered by C. nigoni, suggesting the involvement of differential epistatic interactions in the asymmetric hybrid male fertility and inviability. Importantly, backcrossing of the rescued sterile males with C. nigoni led to the isolation of a 1.1-Mb genomic interval that specifically interacts with an X-linked introgression, which is essential for hybrid male fertility. We further identified three C. briggsae genomic intervals on chromosome I, II, and III that produced inviability in all F1 progeny, dependent on or independent of the parent-of-origin. Taken together, we identified multiple independent interacting loci that are responsible for asymmetric hybrid male and female sterility, and inviability, which lays a foundation for their molecular characterization.

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Reproductive performance of the Antarctic tardigrades, Acutuncus antarcticus (Eutardigrada: Hypsibiidae), revived after being frozen for over 30 years and of their offspring

Zoological Journal of the Linnean Society ◽

10.1093/zoolinnean/zlz137 ◽

2019 ◽

Vol 188 (3) ◽

pp. 839-847

Author(s):

Megumu Tsujimoto ◽

Hiroshi Kagoshima ◽

Hiroshi Kanda ◽

Kenichi Watanabe ◽

Satoshi Imura

Keyword(s):

Reproductive Performance ◽

First Generation ◽

Dna Analysis ◽

Term Survival ◽

Long Term Survival ◽

Genetic Types ◽

Genetic Sequences ◽

The Antarctic ◽

Generation Offspring

Abstract Studies on the long-term survival of animals often focus on the specific instance of survival of animals only, and descriptions of subsequent reproduction are generally not reported. In this study, we recorded the reproductive performance of the first-generation offspring of the resuscitated individual (SB-1) and the hatchling of the resuscitated egg (SB-3) of the Antarctic tardigrade, Acutuncus antarcticus, after being frozen for 30.5 years. By providing further detailed description of the reproduction of SB-1 and SB-3 after revival, and then comparing the reproductive performance with that of their first-generation offspring, the possible indications of the damage accrued during the long-term preservation in SB-1 and SB-3 were more specifically detected. Additionally, the DNA analysis revealed two distinctively different mitochondrial genetic sequences of A. antarcticus between the SB strains and the LSW strain. The observed differences in some of the reproductive parameters between the two genetic types suggested a possible relationship between the life-history traits and genetic type in the species A. antarcticus. Further experiments using the SB-1 and SB-3 strains reared for a long period to exclude the instant effect of preservation are expected to improve our understanding of the mechanisms underlying the long-term survival of animals.

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Sex Differences in Green Ash

Southern Journal of Applied Forestry ◽

10.1093/sjaf/3.4.173 ◽

1979 ◽

Vol 3 (4) ◽

pp. 173-174

Author(s):

John T. Talbert ◽

Robert D. Heeren

Keyword(s):

Sex Differences ◽

First Generation ◽

Tree Improvement ◽

Fraxinus Pennsylvanica ◽

Green Ash ◽

Improvement Program ◽

Male And Female ◽

Sufficient Variation ◽

Natural Stands ◽

Male Superiority

Abstract A disproportionately large number of first-generation selections from natural stands of green ash (Fraxinus pennsylvanica Marsh.) have been male. A study was undertaken to determine if male and female green ash differed in several important economic characteristics. Only straightness differences could be shown to be statistically significant, and, even for this trait, several opinions were needed to detect male superiority. Sufficient variation should exist in natural stands to allow inclusion of superior individuals of both sexes in a tree-improvement program.

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