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Category Archive for 'Immunology'

Epistasis refers to the influence of one genomic mutation or variant on the phenotypic effects of another mutation or variant.  Based on available evidence and theory, this phenomenon has a major influence on evolutionary trajectories for organisms of all sorts.  The role of epistasis has been studied primarily in the context of adaptive evolutionary change.  […]

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Toxoplasma gondii is an intracellular protozoan parasite that infects many different vertebrate species asexually and undergoes a sexual cycle after infecting cats (http://www.cdc.gov/parasites/toxoplasmosis/, 2013).  Parasite oocysts are potentially introduced into the human environment in cat feces.  T. gondii is of interest in clinical medicine because humans can serve as accidental intermediate hosts when they ingest […]

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Geneticists have recognized for some time that many genes exhibit pleiotropy, meaning that one mutation can manifest in two or more distinguishable phenotypic effects. In a fascinating study recently published in Science [2014 Jan 10;343(6167):152-7. doi:10.1126/science.1246886], Joseph et al. offer evidence for an example of pleiotropy in which the distinct phenotypic effects associated with mutation […]

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A careful reading of the review of fever in “Fever: Friend or Foe?”, reveals the embarrassing deficiency in medical science’s understanding of how fever, much less anorexia, functions in infection. Since fever (as well as anorexia and other components of the acute-phase response) is induced by our own cytokines, it is virtually axiomatic that fever […]

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Last month, I completed teaching a graduate course for the tenth time.  After several years (in the early 1990’s) of thinking about launching a new alternate-year seminar course and then planning it, I began teaching PATH 480 in the fall of 1994.  The original name of the course, maintained through the first seven times I […]

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A central focus of recent research aimed at developing a vaccine for HIV-1 is the identification of potent broadly-neutralizing antibodies (bNAbs).  Due to work from several laboratories, many such antibodies have now been identified, produced in quantity as monoclonal antibodies, and characterized with respect to key properties such as epitope specificity, affinity for the corresponding […]

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Currently, I am on vacation near the beach in South Carolina.  Consequently, I have opted for a topic that is bit different than the majority of my monthly commentaries in that it focuses not on a recent original report but instead on a conceptual point made in a book over thirty years ago.  Nevertheless, after […]

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The consortium of investigators known as ENCODE (ENCyclopedia Of DNA Elements) published, with much publicity, a series of about thirty papers last fall purporting to “identify all functional elements in the human genome sequence” (https://www.genome.gov/ENCODE/).  Dan Graur, an evolutionary geneticist at the University of Houston, and his associates have published a paper in Genome Biology […]

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In 1996, Dean et al. (Science), demonstrated that a loss-of-function allele (CCR5Δ32) encoding a version of the chemokine receptor, CCR5, confers very substantial resistance to infection with HIV-1 in the homozygous state and slows progression in the heterozygous state.  Given the relatively recent origin of HIV-1, this finding raised the question of what source of […]

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Influenza A viruses continue to be of enormous interest to biomedical researchers and clinicians alike.  In addition to the annual influenza epidemics, which have been inferred to cause substantial excess mortality, there is the ever-present threat of a global pandemic due to several features of influenza virus biology.  A high mutation rate associated with a […]

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There have been claims that variations in the composition of the intestinal flora influence individual health going back at least to the early years of the 1900s.  Late in his career, Ilya Mechnikov, co-receipient of the Nobel Prize for Physiology or Medicine in 1908 (along with Paul Ehrlich) and a pioneer in the study of […]

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Among the most pressing global public health problems at present is the AIDS epidemic.  While it is clear that chemotherapy and behavioral interventions have much to offer in limiting the spread of infections by the causative virus, HIV-1, interest in developing a vaccine remains strong.  Immunization would potentially provide a relatively cost-effective and scalable approach […]

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In the May 26 (2011) issue of Nature, Vijaykrishna et al. address patterns of evolution and transmission exhibited by swine influenza A viruses (SwIV) isolated from pigs beings slaughtered in Hong Kong between May 1998 and January 2010.  Although the focus of the study is on viruses that circulate in swine, this study is relevant […]

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In his essay (2011) on the history of Darwinian (or evolutionary) medicine, Jonathan Fuller describes potentially relevant interests and insights that preceded the famous paper by Nesse and Williams (1991) that is widely regarded as having catalyzed the resurgence of interest in applying evolutionary concepts and principles to medicine.  For example, the author describes aspects […]

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Among human pathogens, Streptococcus pneumoniae holds an especially prominent place in the history of biomedical investigation.  Griffith (1928) described the transforming principle, a soluble substance released by dead, virulent pneumococci that could render living avirulent pneumococci able to effectively kill a mouse.  Oswald Avery’s commitment to curing pneumococcal pneumonia (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/37) led him and his collaborators […]

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Two recent papers published online at scienceexpress.org describe studies of antibodies claimed to interfere with infection of host cells by a wide range of HIV-1 strains.  These studies strongly suggest that the evolutionary potential of the humoral immune response may be necessary to combat the diversity of HIV-1 antigens that results from the extraordinary pace […]

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In a couple of previous posts I wrote about investigators who harnessed concepts derived from the study of evolution to generate therapeutic agents, in one case for a viral infection (2009a) and in another case for cancer (2009b). Below, I discuss a study from 2009 that illustrates how evolution of cellular populations can undermine treatment […]

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According to both academic lore and history  (Paulos, 1985; Ryerson, 2004), the late Sidney Morgenbesser, a professor of philosophy at Columbia and a renowned conversationalist and wit, was once listening to an Oxford colleague, J. L. Austin, lecturing on the philosophy of language.  The eminent Professor Austin proceeded to claim that while a double negative […]

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I recently saw the movie, “The Blind Side,” based on a book of almost the same name (“The Blind Side: Evolution of a Game”) by author, Michael Lewis. The reference to “evolution” in the book title refers to the adaptations necessitated in the (American) game of football on the offensive line, especially at the left tackle […]

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Sanitizing the hygiene hypothesis: Health lessons from human co-evolution with microorganisms Report from a Workshop led by Kathleen Barnes, Department of Medicine, Johns Hopkins University and Erika von Mutius, Professor of Pediatrics, University Children’s Hospital, Munich One of five workshops in a conference on Evolution and Diseases of Modern Environments Organized by Randolph Nesse, at […]

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