DOCSLIB.ORG

'99 the Genomic Record of Humankind's Evolutionary Roots

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
'99 the Genomic Record of Humankind's Evolutionary Roots View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Am. J. Hum. Genet. 64:31–39, 1999 MOLECULAR EVOLUTION ’99 The Genomic Record of Humankind’s Evolutionary Roots Morris Goodman Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit In response to the call for a human genome–evolution zees are emotionally complex and intelligent. They use project (McConkey and Goodman 1997), the view has tools and have material cultures (McGrew 1992), are been expressed that what makes us human resides in the ecological generalists, are highly social (De Waal 1995; 1.5% difference in genomic DNA that separates us from McGrew et al. 1997), and apparently can learn and use chimpanzees (Gibbons 1998). This view is far too nar- rudimentary forms of language (Savage-Rumbaugh and row. Features that we associate with being human did Lewin 1994; Fouts 1997). In agreement with the newer not just arise de novo in the past 6 million years since information on the social lives and intelligence of chim- the lineage to humans separated from that to chimpan- panzees and other apes (McGrew et al. 1997), the results zees. Rather, some of the most striking human features, of molecular studies of primate phylogeny (Goodman et such as greatly enlarged brains and prolonged child- al. 1998, and in press) challenge the traditional anthro- hoods in social nurturing societies, have deep roots in pocentric view that humans are very different from all our evolutionary history. Forty to 30 million years ago other animals. Rather, the molecular results reveal that (Ma) neocortical portions of the brain increased in the genetically we humans are only slightly remodeled apes. two emerging branches of anthropoid primates—the We share with our most distant living ape relatives (the platyrrhines (or New World monkeys) and the catar- gibbons and siamangs) 195% identity in genomic DNA, rhines. Within the catarrhine branch, additional marked and with our closest relatives (the chimpanzees and bo- enlargements occurred by 18–6 Ma in the lineage to the nobos, or pygmy chimpanzees) 198.3% identity in typ- ancestors of modern hominids, and the largest neocor- ical noncoding DNA and probably ∼99.5% identity in tical increases occurred in the past 3 million years in the the active coding sequences of functional nuclear genes. lineage to modern humans. Traditional primate classifications, still favored by A parallel evolutionary trend prolonged fetal life and many anthropologists, use the nebulous concept of the periods of postnatal life needed to reach full maturity. grades of evolutionary advancement to place both ex- We may surmise that the genetic program for our en- tinct and living small-brained primates—those of the Pa- larged neocortex has both ancient conserved features leocene and Eocene epochs of 65–35 Ma—along with and more-recently derived features—in particular, the the living lemurs, lorises, bush babies, pottos, and tar- anthropoid-specific features shared with New and Old siers, in the suborder Prosimii, the primitive grade. In World monkeys and apes, the hominid-specific features turn, these traditional primate classifications place the shared with apes, and some human-specific features. Al- larger-brained primates in the suborder Anthropoidea, though many mutations in the past 40 million years have the advanced grade. Moreover, within Anthropoidea, a shaped the neurogenetic program for an enlarged neo- gradistic grouping places the African great apes (chim- cortex, it is possible that just a small number of regu- latory mutations in the past 6 million years have brought panzees, bonobos, and gorillas) with the Asian great apes about the final enlargement of our neocortex compared (orangutans) in subfamily Ponginae of family Pongidae, with that of chimpanzees. whereas humans, viewed as the most advanced primates, Behaviorally, the separation between chimpanzees and are the sole living members of family Hominidae. This humans is much smaller than once thought. Chimpan- traditional anthropocentric view of our place in the or- der Primates ignores (1) the overwhelming evidence that the African great apes share their more recent common Received October 19, 1998; accepted for publication November 13, ancestry with humans rather than with orangutans and 1998; electronically published January 13, 1999. (2) the mounting evidence that the clade of chimpanzees Address for correspondence and reprints: Dr. Morris Goodman, De- partment of Anatomy and Cell Biology, Wayne Sate University, 540 and bonobos is the sister group of humans—that is, E. Canfield Ave., Detroit, MI 48201. E-mail: [email protected] shares a more recent common ancestry with humans This article represents the opinion of the author and has not been peer than with gorillas (Goodman et al. 1998). In contrast, reviewed. ᭧ 1999 by The American Society of Human Genetics. All rights reserved. the cladistic view of how to classify organisms calls for 0002-9297/99/6401-0007$02.00 classifying our species, Homo sapiens, in a radically new 31 32 Am. J. Hum. Genet. 64:31–39, 1999 but strictly objective way, one without arbitrary anthro- provide evidence on primate phylogeny represent 61 pri- pocentric biases. In this new way, the cladistic evidence mate species belonging to 41 of the 60 recognized genera from molecules and morphology, as well as the fossil and almost all primate clades with ages older than that and molecular evidence on branch times in primate phy- of genera (Goodman et al., in press). More than 85% logeny, favors a phylogenetic classification (Goodman et of the b-globin gene cluster consists of flanking and in- al. 1998, and in press) in which humans are very close tergenic noncoding sequences that separate the cluster’s to apes, especially to chimpanzees and bonobos. b-type globin genes (e, g, wh, d, and b) from one another, In the derivation of this classification, three principles and these b-type globin genes have twice as much se- proposed by Hennig (1966) were followed. The first quence in their two introns (all noncoding) as in their principle is that each taxon should represent a mono- three exons. Because noncoding sequences evolve at a phyletic group or clade—that is, it should represent all relatively rapid rate and because a majority of the b- species descended from a common ancestor. The second globin gene–cluster sequence data are noncoding, max- principle is that the hierarchical groupings of lower- imum-parsimony trees constructed for each series of ranked taxa into higher-ranked taxa should describe the aligned orthologous sequences in these data have pro- phylogenetic relationships of the clades. The third prin- vided a well-resolved picture of phylogenetic relation- ciple is that, ideally, taxa at the same hierarchical level ships among primate clades. Maximum-likelihood trees, or rank should represent clades that are equally constructed for these aligned sequences, and so-called old—that is, at an equivalent evolutionary age. When neighbor-joining trees, constructed from matrices of these principles are followed, not only do all the apes pairwise distances among the aligned sequences, have group with humans within the family Hominidae, but depicted the same phylogenetic relationships among pri- also chimpanzees and bonobos as one subgenus and hu- mate clades as are depicted in the maximum-parsimony mans as the other subgenus group together into the same trees. genus, Homo. The percentages of sequence change on the branches Below I briefly discuss this classification of primates, of the globin phylogenetic trees were used in conjunction in which humans share their genus with chimpanzees with fossil evidence (reviewed in Goodman et al. 1998) and bonobos. Phylogenetic relationships depicted in the to estimate lineage divergence dates, by means of the classification are supported by DNA hybridization data model of local molecular clocks (Bailey et al. 1992). On and DNA sequence data from the mitochondrial genome the basis of fossil evidence, the lineage divergence date and from a growing number of unlinked nuclear ge- or last common ancestor (LCA) of Old World monkeys nomic loci (reviewed in Goodman et al. 1998, and in (family Cercopithecidae) and humans and apes (family press). Some of the best data come from noncoding se- Hominidae) was placed at 25 Ma, the LCA of platyr- quences of the nuclear genomic region called the “b- rhines and catarrhines at 40 Ma, and the LCA of strep- globin gene cluster.” Phylogenetic analyses of these non- sirhines and haplorhines (i.e., of all living primates) at coding sequences have provided evidence not only on 63 Ma. The paleontologically based age of 25 Ma for primate phylogeny (Goodman et al. 1998) but also on the LCA of cercopithecids and hominids served as the functionally important cis-regulatory elements that con- starting reference date for estimating, from relevant trol the developmental expression of the cluster’s func- branch lengths of the globin phylogenetic trees, the di- tional b-type globin genes, including e, g, and b (Gu- vergence dates for lineages within the hominid clade and mucio et al. 1996). In particular, mutations in cis- separately within the cercopithecid clade. The age of 40 regulatory elements during the emergence and evolution Ma for the LCA of platyrrhines and catarrhines served of the anthropoid primates changed the pattern of g- as the starting date for estimating the divergence dates globin gene expression, from being strictly embryonic to for lineages within the platyrrhine clade. The age of 63 being primarily fetal. These results, too, will be reviewed, Ma for the LCA of strepsirhines and haplorhines served since they illustrate how molecular evolution has shaped as the starting date for estimating the divergence dates functionally important components in the human ge- for lineages within the strepsirhine clade and also for nome.
Load more

Recommended publications
  • Sex Differences in the Social Behavior of Juvenile Spider Monkeys (Ateles Geoffroyi) Michelle Amanda Rodrigues Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 Sex differences in the social behavior of juvenile spider monkeys (Ateles geoffroyi) Michelle Amanda Rodrigues Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Anthropology Commons Recommended Citation Rodrigues, Michelle Amanda, "Sex differences in the social behavior of juvenile spider monkeys (Ateles geoffroyi)" (2007). Retrospective Theses and Dissertations. 14829. https://lib.dr.iastate.edu/rtd/14829 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Sex differences in the social behavior of juvenile spider monkeys (Ateles geoffroyi) by Michelle Amanda Rodrigues A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF ARTS Major: Anthropology Program of Study Committee: Jill D. Pruetz, Major Professor W. Sue Fairbanks Maximilian Viatori Iowa State University Ames, Iowa 2007 Copyright © Michelle Amanda Rodrigues, 2007. All rights reserved. UMI Number: 1443144 UMI Microform 1443144 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii For Travis, Goldie, Clydette, and Udi iii TABLE OF CONTENTS LIST OF TABLES vi LIST OF FIGURES vii ACKNOWLEDGMENTS viii ABSTRACT ix CHAPTER 1.
    [Show full text]
  • The Taxonomy of Primates in the Laboratory Context
    P0800261_01 7/14/05 8:00 AM Page 3 C HAPTER 1 The Taxonomy of Primates T HE T in the Laboratory Context AXONOMY OF P Colin Groves RIMATES School of Archaeology and Anthropology, Australian National University, Canberra, ACT 0200, Australia 3 What are species? D Taxonomy: EFINITION OF THE The biological Organizing nature species concept Taxonomy means classifying organisms. It is nowadays commonly used as a synonym for systematics, though Disagreement as to what precisely constitutes a species P strictly speaking systematics is a much broader sphere is to be expected, given that the concept serves so many RIMATE of interest – interrelationships, and biodiversity. At the functions (Vane-Wright, 1992). We may be interested basis of taxonomy lies that much-debated concept, the in classification as such, or in the evolutionary implica- species. tions of species; in the theory of species, or in simply M ODEL Because there is so much misunderstanding about how to recognize them; or in their reproductive, phys- what a species is, it is necessary to give some space to iological, or husbandry status. discussion of the concept. The importance of what we Most non-specialists probably have some vague mean by the word “species” goes way beyond taxonomy idea that species are defined by not interbreeding with as such: it affects such diverse fields as genetics, biogeog- each other; usually, that hybrids between different species raphy, population biology, ecology, ethology, and bio- are sterile, or that they are incapable of hybridizing at diversity; in an era in which threats to the natural all. Such an impression ultimately derives from the def- world and its biodiversity are accelerating, it affects inition by Mayr (1940), whereby species are “groups of conservation strategies (Rojas, 1992).
    [Show full text]
  • Exam 1 Set 3 Taxonomy and Primates
    Goodall Films • Four classic films from the 1960s of Goodalls early work with Gombe (Tanzania —East Africa) chimpanzees • Introduction to Chimpanzee Behavior • Infant Development • Feeding and Food Sharing • Tool Using Primates! Specifically the EXTANT primates, i.e., the species that are still alive today: these include some prosimians, some monkeys, & some apes (-next: fossil hominins, who are extinct) Diversity ...200$300&species& Taxonomy What are primates? Overview: What are primates? • Taxonomy of living • Prosimians (Strepsirhines) – Lorises things – Lemurs • Distinguishing – Tarsiers (?) • Anthropoids (Haplorhines) primate – Platyrrhines characteristics • Cebids • Atelines • Primate taxonomy: • Callitrichids distinguishing characteristics – Catarrhines within the Order Primate… • Cercopithecoids – Cercopithecines – Colobines • Hominoids – Hylobatids – Pongids – Hominins Taxonomy: Hierarchical and Linnean (between Kingdoms and Species, but really not a totally accurate representation) • Subspecies • Species • Genus • Family • Infraorder • Order • Class • Phylum • Kingdom Tree of life -based on traits we think we observe -Beware anthropocentrism, the concept that humans may regard themselves as the central and most significant entities in the universe, or that they assess reality through an exclusively human perspective. Taxonomy: Kingdoms (6 here) Kingdom Animalia • Ingestive heterotrophs • Lack cell wall • Motile at at least some part of their lives • Embryos have a blastula stage (a hollow ball of cells) • Usually an internal
    [Show full text]
  • The Use of Degraded and Shade Cocoa Forests by Endangered Golden-Headed Lion Tamarins Leontopithecus Chrysomelas
    Oryx Vol 38 No 1 January 2004 The use of degraded and shade cocoa forests by Endangered golden-headed lion tamarins Leontopithecus chrysomelas Becky E. Raboy, Mary C. Christman and James M. Dietz Abstract Determining habitat requirements for threat- consistent across groups. In contrast, all groups preferred ened primates is critical to implementing conservation to sleep in mature or cabruca forest. Golden-headed lion strategies, and plans incorporating metapopulation str- tamarins spent a greater proportion of time foraging and ucture require understanding the potential of available eating fruits, flowers and nectar in cabruca than in habitats to serve as corridors. We examined how three mature or secondary forests. Although the extent to groups of golden-headed lion tamarins Leontopithecus which secondary and cabruca forests can completely chrysomelas in Southern Bahia, Brazil, used mature, sustain breeding groups is unresolved, we conclude that swamp, secondary and shade cocoa (cabruca) forests. both habitats would make suitable corridors for the Unlike callitrichids that show affinities for degraded movement of tamarins between forest fragments, and forest, Leontopithecus species are presumed to depend on that the large trees remaining in cabruca are important primary or mature forests for sleeping sites in tree holes sources of food and sleeping sites. We suggest that and epiphytic bromeliads for animal prey. In this study management plans for golden-headed lion tamarins we quantified resource availability within each habitat, should focus on protecting areas that include access to compared the proportion of time spent in each habitat tall forest, either as mature or cabruca, for the long-term to that based on availability, investigated preferences conservation of the species.
    [Show full text]
  • Veterinary Opposition to the Keeping of Primates As Pets
    Veterinary Opposition to the Keeping of Primates as Pets Introduction: The Humane Society Veterinary Medical Association opposes the private ownership of dangerous and exotic animals. That includes the keeping of primates as pets, since this practice poses a risk to public safety and public health. It is also harmful to the welfare of the primates in question and weakens conservation efforts undertaken to protect their wild counterparts from extinction. The following document describes the compelling case for phasing out the practice of keeping primates as pets, as the majority of states have already done. Primates pose a risk to public safety. Primates are wild animals who have not been – and should not be – domesticated. Given their profound intelligence and behavioral complexity, they are inherently unpredictable, even to primatologists and other experts. Even the smallest monkey species are incredibly strong and can inflict serious injuries with their teeth or nails, including puncture wounds, severe lacerations, and infections. Attacks by apes are frequently disfiguring and can be fatal. Purchased as cute and manageable infants, primates inevitably become aggressive, destructive, and territorial as they mature, often attacking their owners or other people, escaping cages, and causing damage to household items and property. These dangerous and unwanted behaviors are the natural result of forcing these animals to live in environments that are inappropriate physically, psychologically, or socially. When their living conditions fail to permit acceptable outlets for natural behaviors, the result is horror stories that frequently appear on the evening news. Although it is likely that most incidents go unreported, records show that since 1990, more than 300 people— including 105 children—have been injured by captive primates in the United States.1 Some of these attacks have caused permanent disability and disfigurement.
    [Show full text]
  • Diagnosis and Differentiation of the Order Primates
    YEARBOOK OF PHYSICAL ANTHROPOLOGY 30:75-105 (1987) Diagnosis and Differentiation of the Order Primates FREDERICK S. SZALAY, ALFRED L. ROSENBERGER, AND MARIAN DAGOSTO Department of Anthropolog* Hunter College, City University of New York, New York, New York 10021 (F.S.S.); University of Illinois, Urbanq Illinois 61801 (A.L. R.1; School of Medicine, Johns Hopkins University/ Baltimore, h4D 21218 (M.B.) KEY WORDS Semiorders Paromomyiformes and Euprimates, Suborders Strepsirhini and Haplorhini, Semisuborder Anthropoidea, Cranioskeletal morphology, Adapidae, Omomyidae, Grades vs. monophyletic (paraphyletic or holophyletic) taxa ABSTRACT We contrast our approach to a phylogenetic diagnosis of the order Primates, and its various supraspecific taxa, with definitional proce- dures. The order, which we divide into the semiorders Paromomyiformes and Euprimates, is clearly diagnosable on the basis of well-corroborated informa- tion from the fossil record. Lists of derived features which we hypothesize to have been fixed in the first representative species of the Primates, Eupri- mates, Strepsirhini, Haplorhini, and Anthropoidea, are presented. Our clas- sification of the order includes both holophyletic and paraphyletic groups, depending on the nature of the available evidence. We discuss in detail the problematic evidence of the basicranium in Paleo- gene primates and present new evidence for the resolution of previously controversial interpretations. We renew and expand our emphasis on postcra- nial analysis of fossil and living primates to show the importance of under- standing their evolutionary morphology and subsequent to this their use for understanding taxon phylogeny. We reject the much advocated %ladograms first, phylogeny next, and scenario third” approach which maintains that biologically founded character analysis, i.e., functional-adaptive analysis and paleontology, is irrelevant to genealogy hypotheses.
    [Show full text]
  • The Effect of Home Range Reduction on the Ecology of Red Howler Monkeys in Central Amazonia
    THE EFFECT OF HOME RANGE REDUCTION ON THE ECOLOGY OF RED HOWLER MONKEYS IN CENTRAL AMAZONIA by Marcela Santamaría Gómez A dissertation submitted to the University of Cambridge In partial fulfillment of the conditions of application for the Degree of Doctor of Philosophy Wildlife Research Group Selwyn College Department of Anatomy Cambridge University of Cambridge September 2004 To my grandmothers, Mome and Bita, In memoriam “What escapes this eye…is a much more insidious kind of extinction: the extinction of ecological interactions”. D.H. Janzen CONTENTS Preface i Acknowledgements ii Summary v CHAPTER 1 FOREST FRAGMENTATION, AMAZONIA, AND MONKEYS 1.1 Introduction 1.1.1 Tropical deforestation and habitat fragmentation 1 1.1.2 The Amazon 4 1.1.3 Primate, frugivory and seed dispersal 6 1.1.4 Red howler monkeys 9 1.2 Howler monkeys 1.2.1 Howlers in continuous forest 10 1.2.2 Howlers in fragmented habitats 22 CHAPTER 2 RESEARCH DESIGN 2.1 Objectives and questions 30 2.2 Expected results 30 2.3 Study site 2.3.1 Historic background 32 2.3.2 Characteristics of the BDFFP reserves 33 2.3.3 The study sites 36 2.4 General methods 2.4.1 Pre-sampling period 37 2.4.2 Sampling period 40 2.4.3 Group composition 44 2.5 Limitations of this study 47 2.6 Thesis structure 48 CHAPTER 3 FOREST FRAGMENTATION AND CHANGES IN RESOURCE AVAILABILITY 3.1 Introduction 49 3.2 Methods 3.2.1 Rainfall variation 51 3.2.2 Canopy cover 51 3.2.3 Resource availability 52 3.3 Results 3.3.1 Rainfall variation 55 3.3.2 Canopy cover 56 3.3.3 Temporal patterns of trees 57 3.4 Discussion
    [Show full text]
  • An Expanded Search for Simian Foamy Viruses (SFV) in Brazilian New World Primates Identifies Novel SFV Lineages and Host Age‑Related Infections Cláudia P
    Muniz et al. Retrovirology (2015) 12:94 DOI 10.1186/s12977-015-0217-x RESEARCH Open Access An expanded search for simian foamy viruses (SFV) in Brazilian New World primates identifies novel SFV lineages and host age‑related infections Cláudia P. Muniz1,2, Hongwei Jia2, Anupama Shankar2, Lian L. Troncoso1, Anderson M. Augusto3, Elisabete Farias1, Alcides Pissinatti4, Luiz P. Fedullo3, André F. Santos1, Marcelo A. Soares1,5 and William M. Switzer2* Abstract Background: While simian foamy viruses have co-evolved with their primate hosts for millennia, most scientific stud- ies have focused on understanding infection in Old World primates with little knowledge available on the epidemiol- ogy and natural history of SFV infection in New World primates (NWPs). To better understand the geographic and species distribution and evolutionary history of SFV in NWPs we extend our previous studies in Brazil by screening 15 genera consisting of 29 NWP species (140 monkeys total), including five genera (Brachyteles, Cacajao, Callimico, Mico, and Pithecia) not previously analyzed. Monkey blood specimens were tested using a combination of both serology and PCR to more accurately estimate prevalence and investigate transmission patterns. Sequences were phylogeneti- cally analyzed to infer SFV and host evolutionary histories. Results: The overall serologic and molecular prevalences were 42.8 and 33.6 %, respectively, with a combined assay prevalence of 55.8 %. Discordant serology and PCR results were observed for 28.5 % of the samples, indicating that both methods are currently necessary for estimating NWP SFV prevalence. SFV prevalence in sexually mature NWPs with a positive result in any of the WB or PCR assays was 51/107 (47.7 %) compared to 20/33 (61 %) for immature animals.
    [Show full text]
  • Foraging Behavior and Microhabitats Used by Black Lion Tamarins, Leontopithecus Chrysopyqus (Mikan) (Primates, Callitrichidae)
    Foraging behavior and microhabitats used by black lion tamarins, Leontopithecus chrysopyqus (Mikan) (Primates, Callitrichidae) Fernando de Camargo Passos 2 Alexine Keuroghlian 3 ABSTRACT. Foraging in the Black Lion Tamarin (L. chrysopygus Mikan, 1823) was observed in the Caetetus Ecological Station, São Paulo, southeastern Brazil, during 83 days between November 1988 to October 1990. These tamarins use manipuJative, specitic-site foraging behavior. When searching for animal prey items, they examine a variety ofmicrohabitats (dry palm leaves, twigs, under loose bark, in tree cavities). These microhabitats were spatially dispersed among different forest macrohabitats such as swamp torests and dry forested areas. These data indicated that the prey foraging behavior of L. chrysopygus was quite variable, and they used a wide variety ofmicrohabitats, different ofthe other lion tall1arin species. KEY WORDS. Callitrichidae, Leontopithecus chrysopygus, black lion tamarin, ani­ mai prey, foraging behavior, diet, microhabitats Lion tamarins, Leontopithecus Lesson, 1840, are considered primarily in­ sectivores and frugivores (COIMBRA-FILHO & MITTERMEIER 1973), or omnivores (KLElMAN et aI. 1988) because of the diversity of their diet. ln the wild, they consume mostly fruits, exudates, nectar, and animal prey. ln comparison to fruits, animal prey make up a relatively small proportion ofthe diet and are costly to obtain, but its nutritional vai ue make it an essential component of their diet. The prey of black lion tamarins (L. chrysopygus) may include a variety ofinvertebrates (insects, spiders, and other arthropods) and small vertebrates, such as anuran frogs (CARVA­ LHO et aI. 1989; PASSOS 1999). ln this note, we present our observations on prey foraging. We then compare them with studies of other lion tamarin species and discuss some of the unique aspects ofblack lion tamarin foraging in re\ation to the microhabitats they use.
    [Show full text]
  • High-Throughput Human Primary Cell-Based Airway Model for Evaluating Infuenza, Coronavirus, Or Other Respira- Tory Viruses in Vitro
    www.nature.com/scientificreports OPEN High‑throughput human primary cell‑based airway model for evaluating infuenza, coronavirus, or other respiratory viruses in vitro A. L. Gard1, R. J. Luu1, C. R. Miller1, R. Maloney1, B. P. Cain1, E. E. Marr1, D. M. Burns1, R. Gaibler1, T. J. Mulhern1, C. A. Wong1, J. Alladina3, J. R. Coppeta1, P. Liu2, J. P. Wang2, H. Azizgolshani1, R. Fennell Fezzie1, J. L. Balestrini1, B. C. Isenberg1, B. D. Medof3, R. W. Finberg2 & J. T. Borenstein1* Infuenza and other respiratory viruses present a signifcant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID‑ 19. A barrier to the development of efective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low‑throughput animal models. Here, we integrate human primary airway epithelial cells into a custom‑engineered 96‑device platform (PREDICT96‑ALI) in which tissues are cultured in an array of microchannel‑based culture chambers at an air–liquid interface, in a confguration compatible with high resolution in‑situ imaging and real‑time sensing. We apply this platform to infuenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV‑NL63 and SARS‑CoV‑2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confrm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efcacy of camostat mesylate, a known inhibitor of HCoV‑NL63 infection.
    [Show full text]
  • The Common Marmoset in Captivity and Biomedical Research 477 Copyright © 2019 Elsevier Inc
    CHAPTER 26 The Marmoset as a Model in Behavioral Neuroscience and Psychiatric Research Jeffrey A. French Neuroscience Program and Callitrichid Research Center, University of Nebraska at Omaha, NE, United States INTRODUCTION top-down as well as bottom-up regulation of affect and emotion. Finally, the changes in NHP brain struc- In its mission statement, the US National Institutes of ture and function can facilitate the mediation of chal- Health provides a clear statement of its focus: “. to seek lenges associated with group living, including fundamental knowledge about the nature and behavior aggression, affiliation, and the establishment and main- of living systems and the application of that knowledge tenance of long-term complex social relationships that to enhance health, lengthen life, and reduce illness and distinguish these species from nonprimate animals [5]. disability” [emphasis added, www.nih.gov/about-nih/ what-we-do/mission-goals, 2015). Disorders associated with brain or behavioral dysfunction represent the lead- The Utility of Marmosets in Behavioral Models ing disease burden and highest source of lifetime years in Neuroscience and Psychiatric Research living with disability on a global basis (YLD: [1]) and together these disorders represent one of the leading From the perspective of a biomedically oriented contributors to disease-associated mortality worldwide focus, research on behavioral states (both normative [2]. Clearly, then, there is a premium on understanding and atypical) is of interest to the extent that it can pro- both normative behavioral states and their relationship vide useful information regarding the developmental to brain function and the nature of brain dysfunction factors that lead to normative neuropsychological func- as is relates to pathological behavioral states.
    [Show full text]
  • PROCEEDINGS of the OKLAHOMA ACADEMY of SCIENCE Volume 98 2018
    PROCEEDINGS of the OKLAHOMA ACADEMY OF SCIENCE Volume 98 2018 EDITOR: Mostafa Elshahed Production Editor: Tammy Austin Business Manager: T. David Bass The Official Organ of the OKLAHOMA ACADEMY OF SCIENCE Which was established in 1909 for the purpose of stimulating scientific research; to promote fraternal relationships among those engaged in scientific work in Oklahoma; to diffuse among the citizens of the State a knowledge of the various departments of science; and to investigate and make known the material, educational, and other resources of the State. Affiliated with the American Association for the Advancement of Science. Publication Date: January 2019 ii POLICIES OF THE PROCEEDINGS The Proceedings of the Oklahoma Academy of Science contains papers on topics of interest to scientists. The goal is to publish clear communications of scientific findings and of matters of general concern for scientists in Oklahoma, and to serve as a creative outlet for other scientific contributions by scientists. ©2018 Oklahoma Academy of Science The Proceedings of the Oklahoma Academy Base and/or other appropriate repository. of Science contains reports that describe the Information necessary for retrieval of the results of original scientific investigation data from the repository will be specified in (including social science). Papers are received a reference in the paper. with the understanding that they have not been published previously or submitted for 4. Manuscripts that report research involving publication elsewhere. The papers should be human subjects or the use of materials of significant scientific quality, intelligible to a from human organs must be supported by broad scientific audience, and should represent a copy of the document authorizing the research conducted in accordance with accepted research and signed by the appropriate procedures and scientific ethics (proper subject official(s) of the institution where the work treatment and honesty).
    [Show full text]