Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes.

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Effects of crude oil on juvenile threespine stickleback somatic and immune development

10.1101/2021.11.17.469020 ◽

2021 ◽

Author(s):

Kelly S Ireland ◽

Kathryn Milligan-Myhre

Keyword(s):

Crude Oil ◽

Gasterosteus Aculeatus ◽

Oil Spills ◽

Juvenile Fish ◽

Threespine Stickleback ◽

Developmental Defects ◽

Immune Development ◽

Before And After ◽

Important Food Source ◽

Oil Exposure

Aquatic oil spills have resounding effects on surrounding ecosystems, and thus significant resources are committed to oil spill responses to remove the oil from the environment as quickly as possible. Oil has immunotoxic effects and may be particularly harmful to larval and juvenile fish as it can cause a number of developmental defects and stunt growth. In spite of significant efforts to clean oil, it is unclear whether larval and juvenile fish can recover from the effects of oil and no work has been done on the effect crude oil has on developing threespine stickleback (Gasterosteus aculeatus) fish. Threespine stickleback are a ubiquitous sentinel species in the northern hemisphere and are an important food source for many larger, economically valuable fish. As fish with fully marine, anadromous, and freshwater populations, stickleback are exposed to oil in a variety of aquatic environments. We hypothesized that oil exposure would suppress both growth and immunity of developing stickleback, but that fish health could be recovered by removal of the crude oil. Fish were exposed to Alaska North Slope crude oil and then were moved to water without crude oil for two weeks (depuration). Measurements of growth and immunity were taken before and after the depuration. We found that crude oil effected different developmental pathways independently, significantly impacting some but not others. This is the first study to examine the effect crude oil has on early stages of stickleback development, and that stickleback fish are unable to recover from exposure after being transferred to clean water for two-weeks, suggesting larval/juvenile stickleback exposed to crude oil need longer than two-weeks to recover if they are able to recover at all.

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Enzyme activities and maturation in unstimulated and exogenous gonadotropin-stimulated human oocytes

AJP Cell Physiology ◽

10.1152/ajpcell.1993.264.4.c951 ◽

1993 ◽

Vol 264 (4) ◽

pp. C951-C955 ◽

Cited By ~ 7

Author(s):

R. A. Yazigi ◽

M. M. Chi ◽

D. S. Mastrogiannis ◽

R. C. Strickler ◽

V. C. Yang ◽

...

Keyword(s):

Enzyme Activities ◽

Oocyte Quality ◽

Gynecologic Surgery ◽

Vitro Fertilization ◽

Functional Changes ◽

Form And Function ◽

Underlying Mechanisms ◽

Biological Performance ◽

And Function

With the advent of new techniques of human in vitro fertilization (IVF), identifying parameters of oocyte quality to allow selection of those most likely to fertilize becomes crucial. Morphology of oocytes, which correlates positively with biological performance, is the currently utilized classification criterion. However, biological links between form and function are tenuous, and underlying mechanisms remain elusive. We investigated whether biochemical activation is quantitatively associated with the stages of maturation in ova obtained from patients undergoing gynecologic surgery during unstimulated cycles and women undergoing IVF after exogenous gonadotropin stimulation. Changes in selected enzymes from protein, lipid, and carbohydrate metabolism (hexokinase, phosphoglucomutase, glycogen synthetase, uridine diphosphoglucose pyrophosphorylase, glucose-6-phosphate dehydrogenase, cytosolic thiolase, beta-hydroxyacyl-CoA dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) were determined simultaneously, in individual oocytes, utilizing a highly sensitive biochemical methodology. Several enzyme activities paralleled maturation grade and were higher in stimulated oocytes after correction for grade. These biochemical findings quantify metabolic and functional changes that increase as ova mature, possibly contributing to their reproductive performance.

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Decision letter: Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

10.7554/elife.20707.024 ◽

2016 ◽

Keyword(s):

Marine Fish ◽

Adverse Outcome ◽

Chemical Genetics ◽

Adverse Outcome Pathways

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Cardiac dysfunction affects eye development and vision by reducing supply of lipids in fish

10.1101/2021.05.11.443591 ◽

2021 ◽

Author(s):

Elin Sorhus ◽

Sonnich Meier ◽

Carey Elizabeth Donald ◽

Tomasz Furmanek ◽

Rolf Brudvik Edvardsen ◽

...

Keyword(s):

Crude Oil ◽

Channel Blocker ◽

Essential Fatty Acids ◽

Environmental Stressors ◽

Melanogrammus Aeglefinus ◽

Spinal Deformities ◽

Lipid Profiling ◽

Larval Stages ◽

Underlying Mechanisms ◽

Haddock Melanogrammus Aeglefinus

Developing organisms are especially vulnerable to environmental stressors. We aimed to understand the underlying mechanisms of phenanthrene (Phe) and crude oil induced eye malformations. We exposed Atlantic haddock (Melanogrammus aeglefinus) embryos to a known L-type calcium channel blocker, nicardipine hydrochloride (Nic), and compared to early embryonic crude oil (Oil) and late embryonic Phe toxicity. All treatments lead to severe, eye, jaw and spinal deformities at early larval stages. At 3 days post hatching, larvae from all treatments and corresponding controls were dissected. Eyes, trunk, head and yolk sac were subjected to lipid profiling, and eyes were also subjected to transcriptomic profiling. Changes in lipid profiles and the transcriptome suggested that the dysfunctional and abnormal eyes in our treatments were due to both disruption of signaling pathways and insufficient supply of essential fatty acids and other nutrients form the yolk.

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Author response: Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

10.7554/elife.20707.025 ◽

2016 ◽

Author(s):

Elin Sørhus ◽

John P Incardona ◽

Tomasz Furmanek ◽

Giles W Goetz ◽

Nathaniel L Scholz ◽

...

Keyword(s):

Marine Fish ◽

Adverse Outcome ◽

Chemical Genetics ◽

Author Response ◽

Adverse Outcome Pathways

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Scanning tunneling microscopy (STM) of DNA and RNA

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152148 ◽

1989 ◽

Vol 47 ◽

pp. 34-35

Author(s):

Patricia G. Arscott ◽

Gil Lee ◽

Victor A. Bloomfield ◽

D. Fennell Evans

Keyword(s):

Molecular Structures ◽

Inorganic Materials ◽

Resolving Power ◽

Scanning Tunneling ◽

Tunneling Microscopy ◽

Form And Function ◽

Dna And Rna ◽

Calf Thymus ◽

And Function ◽

The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

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