49 Matching Annotations
  1. Aug 2021
    1. genetic material of parvovirus B19 was also detected in early Neolithic skeletal remains, despite the relatively unstable nature of its single-stranded DNA genome

      One of the reasons that DNA is typically easier to recover from ancient samples is that it is usually found as 2 strands twisted together making it more stable. Parvovirus B19 (B19V) has a genome that is a single strand instead of a double, meaning it typically would not last as long in remains. These authors recovered B19V DNA from remains that were between 0.5 and 6.9 thousand years old and demonstrated the virus has been associated with humans for thousands of years.

    2. Most studies on ancient viruses have thus far focused on viruses with a double-stranded DNA genome

      DNA from variola virus which causes smallpox has been recovered from a 300 year old Siberian mummy and a Lithuanian mummy from the 1600's.

      DNA from hepatitis B virus has been recovered from skeletons found in Germany, a 16th century child mummy in Italy, and skeletons scanning a period of nearly 4,000 years from a variety of regions.

    3. molecular clock

      The average speed that a genome accumulates changes to the nucleotide sequence also known as mutations.

    4. sequenced

      DNA and RNA are molecules that provide the code for cells to carry out their functions. They are composed of a small number nucleotides and the order of these nucleotides determines function. Sequencing allows us to determine what the order of nucleotides within a DNA or RNA molecule.

    5. genome

      The full set of genes or heritable genetic material like DNA or RNA present in an organism.

    6. Neolithic revolution

      When humans transitioned from small migrating groups of hunter gatherers to more stationary settlements that focused on farming and raising animals. This led to a significant growth in population sizes.

    7. favorable circumstances, including natural mummification or preservation in cold environments

      Some environments are more likely to preserve genetic material than others. The oldest DNA samples have been recovered from permafrost or regions where the ground remains permanently frozen. Other favorable environments include high salt concentrations, very dry environments like deserts, or environments with very low oxygen like bogs a type of wetland that contains large amounts of dead plant material.

    8. Although the majority of RNA fragments were extremely short (<30 nt), the authenticity of the sequences could be validated

      Given the results demonstrated by Smith and colleagues, the authors decided to look at the size distributions and damage profiled of the RNA recovered from the lung tissue. They found fragments of much greater lengths than 30 nucleotides with fragments ranging from 217-233 nucleotides. They also found no evidence of RNA damage indicating formalin-fixed specimens could serve as a source of well preserved RNA molecules.

    9. RNA was extracted from the remains of a 14,300-year-old Pleistocene canid preserved in permafrost

      Authors generated RNA data from wolf skins and liver tissue of an ancient wolf relative. This is the oldest RNA ever sequenced and the RNA was also tissue specific. This work demonstrates that RNA could possibly be recovered from tissues preserved over thousands of years.

    10. although the directionality of this cross-species transmission event has never been formally established (supplementary text S1)

      In the supplement, the authors use previous studies to assert that while not formally established, the transmission of RPV spilling over into humans is much more likely than the opposite occurrence. They support this with 4 points.

      1. Cattle and other hoofed animal populations were likely large enough to support RPV before human populations were large enough to support measles.
      2. Older descriptions of RPV seem to exist than descriptions of measles.
      3. Other viruses related to measles infect cattle, so it is more likely that RPV infected humans and became measles once rather than measles becoming a cattle virus several times.
      4. Other Paramyxoviruses originated in domesticated animals and jumped to humans. Even with this evidence it cannot be ruled out that transmission from humans to cattle occurred.
    11. with the most reliable (and oldest) estimate falling at the end of the ninth century CE {mean, 899 CE [95% highest posterior density (HPD) interval, 597 to 1144 CE]}

      Wertheim and Pond demonstrate the purifying selection or the removal of damaging alleles can make pathogens seem younger than they really are. Using models that take this phenomenon into account, they provide evidence that the origin of measles is older than previous estimates showed.

    12. divergence time

      The point where rinderpest and measles virus became different species. Virus species are distinguished by a variety of criteria including structural factors, host range, the disease they cause, and genetic similarities.

    13. During the following centuries, introduction of MeV into naive human populations and/or flare-ups of the disease might have caused some ancient epidemics whose etiology remains uncertain.

      Because we do not have sequence data on all outbreaks occurring after measles emerged as a human virus, we cannot say if all outbreaks of similar diseases were caused by measles or a similar related virus that then died out.

    14. Roman sources from the fifth century BCE on

      This book describes the history of outbreaks of disease from cattle in humans from the Roman empire to the 20th century.

    15. numerous concurrent human-bovine epidemics in the early medieval period (here, 6th to 10th centuries CE) were caused by an immediate ancestor of MeV and RPV that was pathogenic to both cattle and humans

      Measles is only able to infect humans, while rinderpest virus is only able to infect cattle. This article provides evidence that outbreaks that occurred during the medieval period were a separate but related virus that was able to infect both cattle and people.

    16. Then, almost as soon as contiguous settlements reached sufficient sizes to maintain the virus’ continuous transmission (Fig. 3), it emerged as a human pathogen, the progenitor of modern-day MeV.

      When human populations were large enough, this virus mutated again and kept spreading throughout human populations. This virus eventually became modern-day measles.

    17. As a fast-evolving RNA virus, it may have produced variants that were able to cross the species barrier on several occasions, but small human populations could only serve as dead-end hosts.

      Bovine virus mutates quickly because it is an RNA virus. It may have mutated so that it was able to infect humans on multiple occasions. However, human populations were not yet at the critical community size, so the virus died out.

    18. Under this scenario, a bovine virus, the common ancestor of modern strains of RPV and MeV, circulated in large populations of cattle (and possibly wild ungulates) since its divergence from PPRV around the fourth millennium BCE [3199 BCE (95% HPD interval, 4632 to 1900 BCE)]

      Before measles became a disease of humans, its predecessor, bovine virus, was common in cattle and possibly other hoofed mammals. This bovine virus was already distinct from peste des petits ruminants virus which is the virus most closely related to it.

    19. there is broad agreement that a number of settlements in North Africa, India, China, Europe, and the Near East began to surpass the CCS for MeV by around 300 BCE, presumably for the first time in human history

      This study assessed regions where major settlements increased in size (upswept) or declined significantly and stayed down without rebounding (downswept). They identified 18 total significant upsweeps including those around 300 BCE.

    20. epidemiologists have held that given the speed with which measles epidemics occur and the efficacy of acquired immunity, MeV could not have become endemic in urban populations below the CCS

      This book provides information on measles expansion, consolidation, and retreat pre and post vaccine introduction within different geographical regions. They present mathematical models to describe the spread of measles epidemics and forecast geographical spread in various conditions.

    21. Retrospective diagnosis

      When the identification of an illness is carried out after a patients death.

    22. Galen

      A Greek physician and surgeon who influenced the development of several medical disciplines.

    23. Hippocratic corpus

      A collection of medical texts from ancient Greece that are attributed to various physicians from the Alexandrian era (4th century BC).

    24. We found a significantly negative coefficient for the time-dependent nonsynonymous/synonymous substitution rate ratio (ω) (11), indicating strong long-term purifying selection;

      Nonsynonymous mutations change the sequence of a protein and are more likely to cause changes in function, while synonymous mutations don't change the protein and are silent in terms of function.

    25. Populations large enough to support continuous MeV transmission—larger than the MeV critical community size (CCS) of 250,000 to 500,000 individuals

      Critical community size (CCS) is the smallest population size that can support the continued persistence of a human-to-human pathogen that is unable to infect animals. Bartlett estimated the critical community size to be around 250,000 using data from Manchester records. Black then used case reports from 19 island communities to establish a CCS of 500,000. Finally, Keeling and Greenfell used prevaccination data from England and Wales and estimated a CCS between 250,000 and 400,000.

    26. The earliest clear clinical description of measles is often attributed to the Persian physician Rhazes, writing in the 10th century CE

      Rhazes was a notable physician who authored more than 200 books and treatises or formal works on subjects like medicine and philosophy. His document "A Treatise on Smallpox and Measles" was the first book to distinguish between the two diseases.

    27. significant additional unexplained variation, as modeled by the random effects
    28. a significantly positive coefficient for the fixed effect on the PPRV rate, indicating a faster evolutionary rate in this clade
    29. Peste des petits ruminants virus

      A virus that causes fever, ulcers of the mouth, pneumonia, stomach problems, and sometimes death in goats and sheep.

    30. The relatedness of the 1912 and 1960 genomes to now extinct MeV lineages is in line with a marked reduction of MeV genetic diversity during the 20th century as a product of massive vaccination efforts.

      When vaccines for measles were introduced the number of people infected declined significantly this caused many strains to die out.

    31. Paramyxoviridae

      A family of viruses that infect vertebrates or animals with a spine. They cause a variety of diseases including measles, mumps, and various respiratory tract infections.

    32. Rudolf Virchow
    33. bronchopneumonia

      Pneumonia is a type of infection causes by a variety of organisms that inflames the lungs. Bronchopneumonia is a type of pneumonia that causes inflammation of a part of the lungs called the alveoli. This inflammation makes it difficult for the lungs to get enough air.

    34. mapped to a MeV genome

      These authors took the collection of overlapping DNA fragments produced through sequencing and lined them up to a genome of measles that had already been constructed.

    35. RNA tends to be much less stable in the environment than DNA, making the recovery of MeV genetic material from archaeological remains unlikely

      RNA degrades more rapidly in the environment because it exists as a single strand while DNA is typically found in a double stranded structure. RNA is also made from ribose while DNA is made with deoxyribose which are two different sugars. The difference in the structure of these sugars makes RNA more susceptible to breaking down when it encounters water.

    36. for example, through the use of ancient viral sequences

      Muhlemann and colleges isolated DNA from ancient human parvovirus 19 and hepatitis B viruses to obtain genomes sequences. These sequences were then used to assess the historical relationship between these viruses and the human population and learn more about viral evolution.

    37. substitution saturation

      This occurs when a nucleotide is switched at the same spot in a gene sequence multiple times. It makes it seem like the rate of sequence divergence is lower than what it actually is.

    38. purifying selection

      Selection refers to natural selection the process by which organisms that are better adapted for their environment survive and produce more offspring. Natural selection causes the evolution of species. Purifying selection removes harmful variations from the population by ensuring those individuals produce fewer offspring.

    39. which is referred to as the time-dependent rate phenomenon

      These studies look at how evolutionary rates change over time and how these alterations can be accounted for in models. Ho and colleagues assert that rates of evolution change over time as a result of a variety of factors and refute the claims of Emerson and Hickerson. Aiewsakun and Katzourakis demonstrated that the time dependence in rate estimates applies for viruses. Accounting for rate variation in can provide more biologically realistic models.

    40. heterochronous

      Chronous refers to time while hetero means different meaning that the measles genomes analyzed were from different timepoints.

    41. It is generally accepted that measles emergence resulted from a spillover from cattle to humans

      Wolfe and colleagues assessed the origin of significant human infectious diseases. They found the origins of diseases varied based on climate and identified stages of a disease transitioning from an animal pathogen to a human pathogen. They found that diseases like measles from mild climates frequently originated from domestic animals like cattle.

  2. Jul 2021
    1. Measles differential diagnosis remained a challenge well into more recent times

      Measles is easily confused with smallpox because they both cause rash and fever. Distinguishing smallpox and measles is no longer a problem since smallpox has been eradicated.

    2. we first heat-treated 200 mg of the formalin-fixed lung tissue to reverse macromolecule cross-links induced by formalin and subsequently performed nucleic acid extraction

      While fixing with formalin preserves biological samples, it causes cross-linking or the chemical joining of molecules. These chemical bonds interfere with the sequencing process. Treating the tissue with heat before purifying the genetic material helps to fix this problem.

    3. substitution rates

      The speed at which mutations occur to a genome.

    4. Bayesian

      Refers to a branch of statistics based on Bayes' theorem. This theorem is used to update the probability or likelihood of a hypothesis or proposed explanation as more information is available. This method allows for inference or the ability to draw conclusions about a larger group based on a smaller sample.

    5. endemic

      A disease is endemic when it is found regularly in a population.

    6. now eradicated
    7. and incidence has recently been on the rise
    8. live-attenuated vaccine

      A vaccine is a substance that causes the body to recognize and stop a disease-causing agent via a type of protein called antibodies. Antibodies combine with proteins on the surface of invading pathogens and alert the immune system. A live-attenuated vaccine uses a weakened for of a virus to cause this immune response.