Tissue folates in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12deficiency and neurological impairment

1. Long-term exposure of the fruit bat Rousettus aegyptiacus to nitrous oxide, which inactivates methylco balamin, leads to neurological impairment and ataxia.2. In N2, O-exposed animals, liver concentrations of total folates and methyl folates decreased to less than one fifth that of control animals. Pediococcus cerevisiue-active folates were also reduced.3. In brain, there were no changes in total or methyl folates, but P.cerevisiae-active folates were lower in N2, O-exposed animals.4. Supplementation with methionine retarded the development of neurological impairment and the fall in liver total and methyl folates, but not that in P. cerevisiae-active folates.5. Supplementation with serine failed to retard the development of neurological impairment or fall in hepatic folates.6. The present results suggest that the N2O-induced neurological impairment in the bat is not related to depletion of cerebral folates, but do not exclude changes in the subcellular distribution of folates.

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Tissue S-adenosylmethionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced neuropathy

British Journal Of Nutrition ◽

10.1079/bjn19830100 ◽

1983 ◽

Vol 50 (2) ◽

pp. 325-330 ◽

Cited By ~ 25

Author(s):

J. van der Westhuyzen ◽

J. Metz

Keyword(s):

Nervous System ◽

Nitrous Oxide ◽

Fruit Bats ◽

Fruit Bat ◽

The Mean ◽

The Brain ◽

Mean Concentration

1. The effect of cobalamin inactivation by the anaesthetic gas nitrous oxide on the concentration of S-adenosylmethionine (Ado Met) in brain and liver of fruit bats (Rousettus aegyptiacus) was examined.2. Test animals exposed to N2O–oxygen (50:50, v/v) developed ataxia and paralysis leading to death after an average of 9·8 weeks (n 6). Animals receiving pteroylmonoglutamic acid supplements in the diet became ataxic earlier (mean 8·8 weeks) while those receiving methionine supplements survived for significantly longer periods (12·5 weeks, P < 0·01).3. Plasma cobalamin levels indicated severe depletion of cobalamin stores in N2O-exposed animals.4. The mean concentration of Ado Met in the brain of N2O-treated bats was nearly 50% higher than that of untreated controls. Ado Met levels in treated bats receiving pteroylmonoglutamic acid or methionine supplements were respectively 18 and 25% higher than in controls. In contrast, the concentration of Ado Met in the liver of all the N2O-treated groups was slightly lower than in controls.5. These results suggest that the N2O-induced neuropathy in the fruit bat is not related to a depletion of Ado Met in the nervous system.

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Betaine Delays the Onset of Neurological Impairment in Nitrous Oxide-Induced Vitamin B-12 Deficiency in Fruit Bats

Journal of Nutrition ◽

10.1093/jn/114.6.1106 ◽

1984 ◽

Vol 114 (6) ◽

pp. 1106-1111 ◽

Cited By ~ 8

Author(s):

Justin van der Westhuyzen ◽

Jack Metz

Keyword(s):

Nitrous Oxide ◽

Neurological Impairment ◽

Vitamin B ◽

Fruit Bats ◽

Vitamin B 12

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Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : Protection by methionine and aggravation by folates

Life Sciences ◽

10.1016/0024-3205(82)90039-x ◽

1982 ◽

Vol 31 (18) ◽

pp. 2001-2010 ◽

Cited By ~ 45

Author(s):

J. van der Westhuyzen ◽

F. Fernandes-Costa ◽

J. Metz

Keyword(s):

Nitrous Oxide ◽

Neurological Impairment ◽

Fruit Bats ◽

Severe Neurological Impairment

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Full genome Nobecovirus sequences from Malagasy fruit bats define a unique evolutionary history for this coronavirus clade

10.1101/2021.09.29.462406 ◽

2021 ◽

Author(s):

Gwenddolen Kettenburg ◽

Amy L Kistler ◽

Hafaliana Christian Ranaivoson ◽

Santino Andry ◽

Joseph L DeRisi ◽

...

Keyword(s):

Full Genome ◽

Fruit Bats ◽

Fecal Samples ◽

Fruit Bat ◽

Long Term Study ◽

Zoonotic Viruses ◽

Globally Distributed ◽

Bat Coronavirus ◽

Generation Sequencing

Bats are natural reservoirs for both Alpha- and Betacoronaviruses and the hypothesized original hosts of five of seven known zoonotic coronaviruses. To date, the vast majority of bat coronavirus research has been concentrated in Asia, though coronaviruses are globally distributed; indeed, SARS-CoV and SARS-CoV-2-related Betacoronaviruses in the subgenus Sarbecovirus have been identified circulating in Rhinolophid bats in both Africa and Europe, despite the relative dearth of surveillance in these regions. As part of a long-term study examining the dynamics of potentially zoonotic viruses in three species of endemic Madagascar fruit bat (Pteropus rufus, Eidolon dupreanum, Rousettus madagascariensis), we carried out metagenomic Next Generation Sequencing (mNGS) on urine, throat, and fecal samples obtained from wild-caught individuals. We report detection of RNA derived from Betacoronavirus subgenus Nobecovirus in fecal samples from all three species and describe full genome sequences of novel Nobecoviruses in P. rufus and R. madagascariensis. Phylogenetic analysis indicates the existence of five distinct Nobecovirus clades, one of which is defined by the highly divergent sequence reported here from P. rufus bats. Madagascar Nobecoviruses derived from P. rufus and R. madagascariensis demonstrate, respectively, Asian and African phylogeographic origins, mirroring those of their fruit bat hosts. Bootscan recombination analysis indicates significant selection has taken place in the spike, nucleocapsid, and NS7 accessory protein regions of the genome for viruses derived from both bat hosts. Madagascar offers a unique phylogeographic nexus of bats and viruses with both Asian and African phylogeographic origins, providing opportunities for unprecedented mixing of viral groups and, potentially, recombination. As fruit bats are handled and consumed widely across Madagascar for subsistence, understanding the landscape of potentially zoonotic coronavirus circulation is essential for mitigation of future zoonotic threats.

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Dissociation of methionine synthetase (EC 2.1.1.13) activity and impairment of DNA synthesis in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency

British Journal Of Nutrition ◽

10.1079/bjn19860022 ◽

1986 ◽

Vol 55 (1) ◽

pp. 187-192 ◽

Cited By ~ 5

Author(s):

Susan V. Van tonder ◽

Angela Ruck ◽

J. Van der Westhuzen ◽

F. Fernandes-costa ◽

J. Metz

Keyword(s):

Bone Marrow ◽

Nitrous Oxide ◽

Dna Synthesis ◽

Vitamin B12 Deficiency ◽

Synthetase Activity ◽

Fruit Bats ◽

Fruit Bat ◽

B12 Deficiency ◽

Suppression Test ◽

Homocysteine Methyltransferase

1. The effect of methylcobalamin inactivation by the anaesthetic gas nitrous oxide on the activity of the cobalamin-dependent methionine synthetase (5-methyltetrahydrofolate homocysteine methyltransferase; EC 2.1. I. 13) reaction, and on DNA synthesis, in the fruit bat Rousettus aegyptiucus, was examined.2. Methionine synthetase activity in the liver of bats exposed to N2O—oxygen (50: 50, v/v) for 90 min/d averaged 32% of that of controls after 4 d of exposure and only 5% after 12–14 weeks of exposure.3. DNA synthesis in the bone marrow, as reflected by the deoxyuridine suppression test, was unaffected by 4 d of exposure to N2O and only minimally affected after 5–10 weeks of exposure.4. These results suggest that DNA synthesis in the fruit bat is unusually resistant to inhibition of methionine synthetase and imply the existence of a non-methylated circulating folate pool in this species.

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Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency

British Journal Of Nutrition ◽

10.1079/bjn19850075 ◽

1985 ◽

Vol 53 (3) ◽

pp. 657-662 ◽

Cited By ~ 13

Author(s):

Justin Van Der Westhuyzen ◽

Suasn V. Van Tonder ◽

Jayne E. Gibson ◽

Terence A. Kilroe-smith ◽

Jack Metz

Keyword(s):

Nitrous Oxide ◽

Vitamin B12 Deficiency ◽

Dietary Supplementation ◽

Basal Diet ◽

Neurological Impairment ◽

Vitamin B ◽

Muscular Weakness ◽

Fruit Bats ◽

B12 Deficiency ◽

Methionine Synthesis

1. The effect of methylcobalamin inactivation by the gas nitrous oxide on plasma amino acid and tissue methionine levels in fruit bats (Rousettus aegyptiacus) was examined.2. Animals exposed to N2O-oxygen (1:1, v/v) for 90 min daily received a fruit diet with or without methionine or betaine supplements. Exposure and diets were continued for up to 17 weeks or until neurological impairment and muscular weakness was established.3. All the groups exposed to N2O had significantly lower liver, brain and plasma methionine concentrations except the methionine-supplemented animals which showed significantly raised levels. Plasma homocysteine, which was absent in controls, was present in all the N2O-exposed groups.4. Betaine supplementation resulted in reduced accumulation of homocysteine in plasma. However, plasma and liver methionine levels were only slightly increased compared with animals on the basal diet, and brain methionine levels were the lowest of all the groups studied.5. These results support the hypothesis that reduced methionine synthesis is an important contributor to the development of neurological impairment in this species and suggest that dietary supplementation with the methionine precursor betaine cannot replace the loss of vitamin B12-dependent methionine synthesis.

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Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life

Nature Communications ◽

10.1038/s41467-021-23468-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Najeh Hcini ◽

Yaovi Kugbe ◽

Zo Hasina Linah Rafalimanana ◽

Véronique Lambert ◽

Meredith Mathieu ◽

...

Keyword(s):

Neurological Impairment ◽

In Utero ◽

In Utero Exposure ◽

Zikv Infection ◽

Neurodevelopmental Delay ◽

Systematic Testing ◽

Brain Anomalies ◽

Increased Risk ◽

Structural Brain

AbstractLittle is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5–29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2–20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9–10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

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Long-Term Fertilization Alters Nitrous Oxide Cycling Dynamics in Salt Marsh Sediments

Environmental Science & Technology ◽

10.1021/acs.est.1c01542 ◽

2021 ◽

Author(s):

Xuefeng Peng ◽

Qixing Ji ◽

John H. Angell ◽

Patrick J. Kearns ◽

Jennifer L. Bowen ◽

...

Keyword(s):

Nitrous Oxide ◽

Salt Marsh ◽

Marsh Sediments ◽

Salt Marsh Sediments

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Informed Consent for the Human Research Subject with a Neurologic Disorder

Seminars in Neurology ◽

10.1055/s-0038-1668077 ◽

2018 ◽

Vol 38 (05) ◽

pp. 539-547 ◽

Cited By ~ 1

Author(s):

Neil Vaishnav ◽

Winston Chiong

Keyword(s):

Informed Consent ◽

Neurological Impairment ◽

Neurological Injury ◽

Neurologic Disorder ◽

Legal Principles ◽

Human Research Subject ◽

Neurological Patients ◽

Dementia Research ◽

To Come

AbstractThe doctrine of informed consent sits at the intersection of law, ethics, and neuroscience, posing unique challenges for human subject research involving neurological patients. These challenges are compounded by the variegated nature of both neurological injury and the law governing research consent. This article provides a framework for investigators likely to encounter subjects with some degree of neurological impairment, whose capacity to consent requires scrupulous assessment prior to enrollment in research trials. We consider several researches and disease contexts—from emergency epilepsy research to long-term dementia research—and clarify the ethical and legal principles governing consent for participation in each. We additionally explore empirical research on consent capacity and survey several areas of emerging ethical import that will require the attention of investigators in decades to come.

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