Evolution, Medicine, and Public Health最新文献

{"title":"Response to genes that improved fitness also cost modern humans: evidence for genes with antagonistic effects on longevity and disease.","authors":"Steven N Austad, Jessica M Hoffman","doi":"10.1093/emph/eoz003","DOIUrl":"https://doi.org/10.1093/emph/eoz003","url":null,"abstract":"Byars and Voskarides, responding to our review of empirical support for George Williams’ antagonistic pleiotropy (AP) theory of the evolution of aging [1], feel that we have ‘failed to acknowledge’ recent human studies supporting the theory. Indeed, we mentioned no human studies because we had intended our review to present only the strongest evidence supporting the theory which has been done almost entirely in laboratory model organisms. For this reason, while we mentioned a few studies from natural populations, we emphasized how such nonexperimental studies could be consistent with the AP mechanisms, but could not be cleanly attributed to it. Thus, we focused on experimental studies—those in which experimental manipulation of a single gene had clear antagonistic effects on fitness components in early versus late life as Williams predicted. Experimental studies establish cause-and-effect in a way that correlational studies such as those cited by Byars and Voskarides cannot. It is an unfortunate truth about research on humans that because experimental studies are often impossible, results are almost inevitably correlational, which in our view makes virtually any single study highly suggestive at best, but never compelling. To illustrate why, we consider one of the studies adduced by Byars and Voskarides, although we could have chosen any of the others. That study identifies numerous human alleles (or Single nucleotide Polymorphisms) pre-disposing individuals to coronary artery disease (CAD) but also conferring reproductive advantages early in life [2]. As to the nature of the evidence they presented, they identified a correlation, e.g. signs of positive correspondence 7","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"7-8"},"PeriodicalIF":3.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoz003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9289676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial comment: Pre-eclampsia.","authors":"Gillian R Bentley","doi":"10.1093/emph/eoy030","DOIUrl":"https://doi.org/10.1093/emph/eoy030","url":null,"abstract":"P re-eclampsia (PE), marked symptomatically by increased blood pressure, renal or liver insufficiency, cerebral disturbances, excessive protein in urine (proteinuria) or low platelet levels and edema is a potentially fatal condition that affects a small proportion (estimated at 4.6%) of women around the globe [1]. Risk for women is increased by twin or higher gestations, age, primipaternity, an elevated body mass index, metabolic disorders and smoking among other factors [1]. The pathophysiology of this disease is otherwise not well understood; treatment is limited to alleviating symptoms and, in more severe cases, inducing labour or performing pre-term C-sections [2]. Maternal mortality associated with the condition is low relative to deaths experienced during labour and delivery, but presumably higher in regions where good medical facilities are absent. Due to the relatively small numbers of women who experience PE, it would be rarely documented among populations such as hunter-gatherers where lifestyles are presumably closer to those in which our species evolved. Apes (with among the most highly invasive trophoblasts) are the only species thought to experience this condition [3]. Evolutionary perspectives on this condition emerged with David Haig’s publication on parental genetic conflicts [4]. He argued that paternally derived genes will attempt to mediate additional resources to aid foetal growth, while maternally derived genes will attempt to control these resources in the interest of future reproductive effort. It is this conflict that, allegedly, leads to PE in mid-to-late pregnancy. Clinical studies of PE generally do not contextualize its potential evolutionary origin, but focus instead on potential proximate causes for the condition such as twin or higher gestations, age, smoking and metabolic disorders, although some sources acknowledge risk factors such as primipaternity which may also have an adaptive function. Clinical Briefs in EMPH provide short reviews of evolutionary approaches to pathologies or conditions in order to broaden the scope of thinking in medicine and public health, and that could help in finding novel treatments. Serendipitiously, two complementary Clinical Briefs on the topic of PE were simultaneously submitted to EMPH by separate sets of authors [5, 6]; we are publishing them together and briefly highlight specific contrasts. Although both focus on the genetic conflict model described above as well as immunological dysfunctions known to increase risk for PE, Varas Enriquez et al. (2018) also discuss how the nutritional requirements of large-brained infants may have exacerbated genetic conflicts during gestation. They draw attention to the suggestion that low rates of human fecundability function to increase sexual exposure to partners prior to conception, thereby lowering PE risk. editorial 295","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"295-296"},"PeriodicalIF":3.7,"publicationDate":"2018-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36812539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation among populations in the immune protein composition of mother's milk reflects subsistence pattern.","authors":"Laura D Klein, Jincui Huang, Elizabeth A Quinn, Melanie A Martin, Alicia A Breakey, Michael Gurven, Hillard Kaplan, Claudia Valeggia, Grazyna Jasienska, Brooke Scelza, Carlito B Lebrilla, Katie Hinde","doi":"10.1093/emph/eoy031","DOIUrl":"10.1093/emph/eoy031","url":null,"abstract":"<p><strong>Lay summary: </strong>Adaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.</p><p><strong>Background and objectives: </strong>Mother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.</p><p><strong>Methodology: </strong>Milk samples (<i>n</i> = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.</p><p><strong>Results: </strong>Both innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.</p><p><strong>Conclusions and implications: </strong>Our results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"230-245"},"PeriodicalIF":3.7,"publicationDate":"2018-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36725470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is antagonistic pleiotropy ubiquitous in aging biology?","authors":"Steven N Austad,&nbsp;Jessica M Hoffman","doi":"10.1093/emph/eoy033","DOIUrl":"10.1093/emph/eoy033","url":null,"abstract":"<p><p>Lay Summary: An evolutionary mechanism of aging was hypothesized 60 years ago to be the genetic trade-off between early life fitness and late life mortality. Genetic evidence supporting this hypothesis was unavailable then, but has accumulated recently. These tradeoffs, known as antagonistic pleiotropy, are common, perhaps ubiquitous. George Williams' 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge. No genes of the sort hypothesized by Williams were known 60 years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams' hypothesis? What are the implications of Williams' hypothesis for the modern goal of medically intervening to enhance and prolong human health? Here we briefly review the current state of knowledge on antagonistic pleiotropy both under wild and laboratory conditions. Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"287-294"},"PeriodicalIF":3.7,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36760304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ecosystem framework for understanding and treating disease.","authors":"Michael E Hochberg","doi":"10.1093/emph/eoy032","DOIUrl":"https://doi.org/10.1093/emph/eoy032","url":null,"abstract":"<p><p>Pathogens and cancers are pervasive health risks in the human population. I argue that if we are to better understand disease and its treatment, then we need to take an ecological perspective of disease <i>itself</i>. I generalize and extend an emerging framework that views disease as an ecosystem and many of its components as interacting in a community. I develop the framework for biological etiological agents (BEAs) that multiply within humans-focusing on bacterial pathogens and cancers-but the framework could be extended to include other host and parasite species. I begin by describing why we need an ecosystem framework to understand disease, and the main components and interactions in bacterial and cancer disease ecosystems. Focus is then given to the BEA and how it may proceed through characteristic states, including emergence, growth, spread and regression. The framework is then applied to therapeutic interventions. Central to success is preventing BEA evasion, the best known being antibiotic resistance and chemotherapeutic resistance in cancers. With risks of evasion in mind, I propose six measures that either introduce new components into the disease ecosystem or manipulate existing ones. An ecosystem framework promises to enhance our understanding of disease, BEA and host (co)evolution, and how we can improve therapeutic outcomes.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"270-286"},"PeriodicalIF":3.7,"publicationDate":"2018-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36776466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza, evolution, and the next pandemic.","authors":"David S Fedson","doi":"10.1093/emph/eoy027","DOIUrl":"https://doi.org/10.1093/emph/eoy027","url":null,"abstract":"<p><p>Mortality rates in influenza appear to have been shaped by evolution. During the 1918 pandemic, mortality rates were lower in children compared with adults. This mortality difference occurs in a wide variety of infectious diseases. It has been replicated in mice and might be due to greater tolerance of infection, not greater resistance. Importantly, combination treatment with inexpensive and widely available generic drugs (e.g. statins and angiotensin receptor blockers) might change the damaging host response in adults to a more tolerant response in children. These drugs might work by modifying endothelial dysfunction, mitochondrial biogenesis and immunometabolism. Treating the host response might be the only practical way to reduce global mortality during the next influenza pandemic. It might also help reduce mortality due to seasonal influenza and other forms of acute critical illness. To realize these benefits, we need laboratory and clinical studies of host response treatment before and after puberty.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"260-269"},"PeriodicalIF":3.7,"publicationDate":"2018-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autism, evolution, and the inadequacy of 'spectrum'.","authors":"Neil S Greenspan","doi":"10.1093/emph/eoy025","DOIUrl":"https://doi.org/10.1093/emph/eoy025","url":null,"abstract":"<p><p>Lay Summary: Individuals diagnosed with autism display variation in many traits, such as interest and ability in social interaction or resistance to change. Referring to this variation as a 'spectrum', defined as a range of values along an axis, understates the extent of such variation and can foster incorrect inferences. In psychiatry, the currently accepted term for a developmental disability characterized by variably impaired social and communicative skills, repetitive behaviors, and restricted interests is \"autism spectrum disorder.\" \"Spectrum,\" typically refers to values of a variable distributed along a single dimension, incorrectly suggesting people with autism can be simply ranked as more or less 'autistic.' In fact, there are multiple traits that pertain to autism and that can vary somewhat independently, in part due to the evolutionary mechanisms that give rise to risk alleles. Therefore, a new and more accurate clinical descriptor should be adopted. I propose: autism-related disorders (ARD).</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"213-216"},"PeriodicalIF":3.7,"publicationDate":"2018-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36620819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-eclampsia: Understanding clinical complexity.","authors":"Arjen R Buschman,&nbsp;Annelies Rep","doi":"10.1093/emph/eoy028","DOIUrl":"https://doi.org/10.1093/emph/eoy028","url":null,"abstract":"Worldwide 2–8% of pregnancies are complicated by pre-eclampsia (PE), with an estimated maternal mortality of 50 000 cases annually [1]. PE is a part of the hypertensive syndrome of pregnancy and is defined as hypertension (4 140/ 90 mmHg) with proteinuria (4 300 mg/ 24 h). Symptoms of PE commence in the second half of pregnancy. These might encompass general symptoms of hypertension and/or proteinuria such as headache, exhaustion, nausea, vomiting, visual disorders and edema. Multiple organs can be affected causing severe complications such as eclampsia or progress to HELLPsyndrome. Delivery is the only definitive treatment. In preterm stages of pregnancy treatment of the disease occurs mainly symptomatically, aiming for analgesia and control of hypertension. In high-risk groups, a slight risk reduction of developing PE is achieved by administration of acetylsalycic acid in early pregnancy [2]. A century of research has not yet given physicians more powerful tools to protect both maternal and fetal conditions (Fig. 1). PATHOPHYSIOLOGY","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"211-212"},"PeriodicalIF":3.7,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36587031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-eclampsia and maternal-fetal conflict.","authors":"P J Varas Enriquez,&nbsp;L J McKerracher,&nbsp;M G Elliot","doi":"10.1093/emph/eoy029","DOIUrl":"https://doi.org/10.1093/emph/eoy029","url":null,"abstract":"Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada, and Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands *Corresponding author. Groningen Institute for Evolutionary Life Sciences, University of Groningen, PO Box 11103, 9700 CC Groningen, The Netherlands. Telephone: +31 50 36 32356. E-mail: m.g.elliot@rug.nl","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"217-218"},"PeriodicalIF":3.7,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36628664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the evolutionary robustness of two repurposed drugs targeting iron uptake in <i>Pseudomonas aeruginosa</i>.","authors":"Chiara Rezzoagli,&nbsp;David Wilson,&nbsp;Michael Weigert,&nbsp;Stefan Wyder,&nbsp;Rolf Kümmerli","doi":"10.1093/emph/eoy026","DOIUrl":"10.1093/emph/eoy026","url":null,"abstract":"<p><strong>Lay summary: </strong>We probed the evolutionary robustness of two antivirulence drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine in the opportunistic pathogen <i>Pseudomonas aeruginosa</i>. Using an experimental evolution approach in human serum, we showed that antivirulence treatments are not evolutionarily robust per se, but vary in their propensity to select for resistance.</p><p><strong>Background and objectives: </strong>Treatments that inhibit the expression or functioning of bacterial virulence factors hold great promise to be both effective and exert weaker selection for resistance than conventional antibiotics. However, the evolutionary robustness argument, based on the idea that antivirulence treatments disarm rather than kill pathogens, is controversial. Here, we probe the evolutionary robustness of two repurposed drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine of the opportunistic human pathogen <i>Pseudomonas aeruginosa</i>.</p><p><strong>Methodology: </strong>We subjected replicated cultures of bacteria to two concentrations of each drug for 20 consecutive days in human serum as an <i>ex vivo</i> infection model. We screened evolved populations and clones for resistance phenotypes, including the restoration of growth and pyoverdine production, and the evolution of iron uptake by-passing mechanisms. We whole-genome sequenced evolved clones to identify the genetic basis of resistance.</p><p><strong>Results: </strong>We found that mutants resistant against antivirulence treatments readily arose, but their selective spreading varied between treatments. Flucytosine resistance quickly spread in all populations due to disruptive mutations in <i>upp</i>, a gene encoding an enzyme required for flucytosine activation. Conversely, resistance against gallium arose only sporadically, and was based on mutations in transcriptional regulators, upregulating pyocyanin production, a redox-active molecule promoting siderophore-independent iron acquisition. The spread of gallium resistance was presumably hampered because pyocyanin-mediated iron delivery benefits resistant and susceptible cells alike.</p><p><strong>Conclusions and implications: </strong>Our work highlights that antivirulence treatments are not evolutionarily robust <i>per se</i>. Instead, evolutionary robustness is a relative measure, with specific treatments occupying different positions on a continuous scale.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2018 1","pages":"246-259"},"PeriodicalIF":3.7,"publicationDate":"2018-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoy026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}