Lamark's Nose: Genetic imprinting and Inherited Memories of Trauma in Mice

One of the implications of the current Mendelian synthesis in molecular genetics is the idea that natural selection operates via selecting on random variations in the gene pool, which themselves are not influenced by the environmental experiences of the reproducing organisms. Changes of a given organism's body due to experience, such as conditioning, trauma, and memory, are usually assumed to only affect the gene pool of the next generation by influencing how many progeny are produced and raised by the prior generation. This is, however, not the whole story.

Epigenetics is the study of how gene expression changes during the growth and development of an organism. For example, the fertilized egg will divide and grow, not just into a clump of egg cells, but a fully differentiated organism containing many different kinds of specialized cells and tissues. Most of these calls contain the same genetic information as the original fertilized ovum, but the DNA has been subtly modified to make specialized groups of RNA and thus proteins.

The biology of epigenetics thus explains how the same DNA information produces different effects in different cells. Can such changes be inherited? Certainly in plants, they can be. It can be shown that sprouting root tissue from a tree often produces a differently shaped plant than sprouting a branch from the same tree. One way that this occurs is via methylation of the cytosine of a DNA region to make it into nonfunctional, mutation-promoting 5-methycytosine. When such changes in DNA--either in its cytosine or its associated histones--are passed to offspring, this has been called genetic imprinting.

In the journal Nature Neuroscience, Brian Dias and Kerry Ressler seem to have found a way that rodents use such genetic imprinting to create a survival advantage: via inheritance of fear of a certain smell. The researches seem to have found that conditioning an olfactory stimulus as adversive makes that stimulus' adversiveness inheritable in the offspring, and that this information is passed via a decreased methylation of the mouse's sperm DNA encoding those particular smell receptors as adversive to the mouse.

A future question is how a signal given to the nose can actually change the methylation of DNA in produced sperm. But we may have here an explanation for the rapid development of innate fear of a predator (including man) in the offspring of animals newly exposed to such.

Will Lamark score a partial comeback in biology? Time will tell.


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ABSTRACT

Parental olfactory experience influences behavior and neural structure in subsequent generations

Brian G Dias & Kerry J Ressler

Nature Neuroscience 17, 89–96 (2014)

doi:10.1038/nn.3594

Received 21 September 2013 Accepted 01 November 2013 Published online 01 December 2013 Corrected online 09 December 2013

Using olfactory molecular specificity, we examined the inheritance of parental traumatic exposure, a phenomenon that has been frequently observed, but not understood. We subjected F0 mice to odor fear conditioning before conception and found that subsequently conceived F1 and F2 generations had an increased behavioral sensitivity to the F0-conditioned odor, but not to other odors. When an odor (acetophenone) that activates a known odorant receptor (Olfr151) was used to condition F0 mice, the behavioral sensitivity of the F1 and F2 generations to acetophenone was complemented by an enhanced neuroanatomical representation of the Olfr151 pathway. Bisulfite sequencing of sperm DNA from conditioned F0 males and F1 naive offspring revealed CpG hypomethylation in the Olfr151 gene. In addition, in vitro fertilization, F2 inheritance and cross-fostering revealed that these transgenerational effects are inherited via parental gametes. Our findings provide a framework for addressing how environmental information may be inherited transgenerationally at behavioral, neuroanatomical and epigenetic levels.

Why Don't Multi-Vitamins Work?

The journal Annals of Internal Medicine this month carries three studies which suggest that vitamin supplementation does not improve health in the general population. (They exempt vitamin D3, which is likely deficient in a large swath of the American population).

Yet multiple prior studies show that a diet of fruit and vegetables high in exactly those vitamins DOES improve health. The current CDC diet recommendations reflect this.

Why the lack of correlation between added multivitamins and health, yet a diet recommending foods rich in vitamins?

There is reason to think that there are aspects of fresh fruits and vegetables that cannot be duplicated in a vitamin tablet, such as the mix of fiber, trace minerals, and complex proteins and lipids which are lacking in ordinary supplemental vitamins and are probably degraded in any attempted reduction for packaging as altenative supplements, such as that done when herbs are processed for placement into capsules. There may simply be no known way to replace fresh produce as a major part of a healthy diet.

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Editorials | 17 December 2013

Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements

Eliseo Guallar, MD, DrPH; Saverio Stranges, MD, PhD; Cynthia Mulrow, MD, MSc, Senior Deputy Editor; Lawrence J. Appel, MD, MPH; and Edgar R. Miller III, MD, PhD

[+] Article and Author Information

See Also:

Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force

Ann Intern Med. 2013;159(12):850-851-851.

doi:10.7326/0003-4819-159-12-201312170-00011

Article

References

In this issue, 3 articles address vitamin and mineral supplements for prevention of chronic diseases. The editorialists discuss the articles' findings and their implications for public health and research. They conclude that most mineral and vitamin supplements have no clear benefit, might even be harmful in well-nourished adults, and should not be used for chronic disease prevention.

Rotavirus Vaccine Prevents Seizures in Children

Rotavirus infections, along with other febrile virus infections in childhood and adulthood, have long been linked to epilepsy in infants and children. A recently published study has shown that vaccination against rotavirus decreases seizures in children for at least the year following vaccination.

The risk of a seizure was decreased by 119 out of 100,000 person-years. Contrast this with a total increased risk of seizure after three pertussis immunizations of less than 32 out of 100,000. A series of 3 rotavirus immunizations was almost 4 times more effective at preventing seizures than a series of 3 pertussis immunizations was, perhaps, at inducing them.

Some parents may have been made cautious about allowing their children to be immunized, in general, against any infection, after media reports of seizures and brain disease following pertussis immunization. Now that we have a clear example of immunization protecting against seizures, will we see media hype about the benefit of vaccines?

That will probably not happen, of course. Don't hold your breath waiting for that outcome.


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Protective Association Between Rotavirus Vaccination and Childhood Seizures in the Year Following Vaccination in US Children

Daniel C. Payne1, James Baggs2, Danielle M. Zerr3,4, Nicola P. Klein5, Katherine Yih6, Jason Glanz7, Aaron T. Curns1, Eric Weintraub8, and Umesh D. Parashar1

+ Author Affiliations

1Epidemiology Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases 2Prevention and Response Branch, Division of Healthcare Quality Promotion, National Center for Zoonotic and Emerging Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 3Department of Pediatrics, University of Washington, Seattle 4Seattle Children's Research Institute, Washington 5Kaiser Permanente Vaccine Study Center, Kaiser Permanente, Oakland, California 6Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts 7Institute for Health Research, Kaiser Permanente Colorado, Denver 8Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Zoonotic and Emerging Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia Correspondence: Daniel C. Payne, PhD, MSPH, Division of Viral Diseases, Epidemiology Branch, CDC, 1600 Clifton Rd NE, MS-A34, Atlanta, GA 30333 (dvp6@cdc.gov).

Abstract

Background. Rotavirus illness has been linked to childhood seizures. We investigated whether a protective association exists between receipt of rotavirus vaccine and being hospitalized or visiting the emergency department for seizures in the year after vaccination.

Methods. We retrospectively analyzed a cohort of children born after 28 February 2006 (when rotavirus vaccine was licensed in the United States) and enrolled in the Vaccine Safety Datalink (VSD) through November 2009. Seizure rates from 4 to 55 weeks following last rotavirus vaccination were compared by vaccine exposure status (fully vaccinated and unvaccinated). A time-to-event analysis using a Cox proportional hazards model was performed, accounting for time-varying covariates. We calculated the relative incidence of seizure compared by vaccine exposure status during the postexposure interval.

Results. Our cohort contained VSD data on 250 601 infants, including 186 502 children fully vaccinated (74.4%) and 64 099 (25.6%) not vaccinated with rotavirus vaccine. Rates of seizures were associated with rotavirus vaccination status. After adjusting for covariates (VSD site, age at last dose, sex, and calendar month of the index date), a statistically significant protective association was observed between a full course of rotavirus vaccination vs no vaccination for both first-ever seizures (risk ratio [RR] = 0.82; 95% confidence interval [CI], .73–.91) and all seizures (RR = 0.79; 95% CI, .71–.88).

Conclusions. A full course of rotavirus vaccination was statistically associated with an 18%–21% reduction in risk of seizure requiring hospitalization or emergency department care in the year following vaccination, compared with unvaccinated children. This reduction in childhood seizures complements the well-documented vaccine-related benefit of preventing US diarrhea hospitalizations.


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JAMA. 2012 Feb 22;307(8):823-31. doi: 10.1001/jama.2012.165.

Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.

Sun Y, Christensen J, Hviid A, Li J, Vedsted P, Olsen J, Vestergaard M.

Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000 Aarhus C, Denmark. ys@soci.au.dk

CONTEXT: Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.

OBJECTIVE: To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.

DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of 378,834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.

MAIN OUTCOME MEASURES: Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.

RESULTS: A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000 person-days), 32 children after the second (1.3 per 100,000 person-days), and 201 children after the third (8.5 per 100,000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100,000 person-days), 12 children after the second (5.7 per 100,000 person-days), and 27 children after the third (13.1 per 100,000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.

CONCLUSIONS: DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

PMID: 22357833 [PubMed - indexed for MEDLINE]

On the Vagueness of Species, Part 2: On the Vagueness of Organisms

Above we see a video schematic of Hepatitis B, one of the smallest human viruses at 42 nm. Whether viruses are living things or not has been a matter of debate. Requiring a living, much larger host in order to reproduce is not exclusive to viruses.

The presence of vagueness, of border cases, among organisms between living and not-living things has been a source of frustration for some biologists. If we require of our concept of reality a rigid, medieval essentialism, like that of some who assert the reality of hard edged taxa in dividing species, we are going to be frustrated at the lack of a clearly defined border between life and non-life.

Why? Because life, like most of the categories of human experience, is a vague category.

Unfortunately, there are those whose tolerance of vagueness is very poor. Scientific American blogger Ferris Jabr is one. Faced with vagueness, he denies the category. This makes for interesting reading, given the way the pig of absurdity is dressed in well written prose.

The problem is the promiscuity of skepticism about the world when exact boundaries are elusive to scientific investigation. Let's look at an example: the air we breathe.

Does the air we breathe exist? It appears it does not. If we look at air at the atomic scale, there are only molecules in constant motion, and each individual molecule lacks all of the qualities of our air, except mass. Most of the molecules, which are made of a pair of nitrogen atoms, cannot be used by the body for its metabolism, and we would thus suffocate if we tried to breathe those atoms alone. Furthermore, there is no boundary to the atmosphere we can place in any exact sense. As we ascend in altitude, the air thins more and more, but there is no exact, distinct point where the air ends. Without a firm boundary between air and not-air, the atmosphere cannot be a real thing: it is a mere artifact of our language. The air we breathe, therefore, does not exist.

Using an extension of this argument, it is easy to "prove" that the Sun, the planets, the solar system, and the galaxy do not exist. We merely need to point out that such things are very different from their components and that they have a poorly defined physical boundary.

The fallacy of claiming that all the properties of a category (life) must be the property of its components (individual organisms), including its boundary cases, is a type of fallacy of division, also called the modo hoc fallacy. The fallacy of claiming that a vaguely defined thing cannot exist is called the continuum fallacy, which is Ferris Jabr's fallacy.

(HT: Bill Vallicella).

Multiple sclerosis and the Gut Microbiome: Some Preclinical Results

The gut microbiome is measured by assessing the prokaryotic DNA of a stool sample, which reflects the various types of bacteria that are g...