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  1. Article: Genetic evidence of population subdivision among Masai giraffes separated by the Gregory Rift Valley in Tanzania.

    Lohay, George G / Lee, Derek E / Wu-Cavener, Lan / Pearce, David L / Hou, Xiaoyi / Bond, Monica L / Cavener, Douglas R

    Ecology and evolution

    2023  Volume 13, Issue 6, Page(s) e10160

    Abstract: The Masai giraffe has experienced a population decline from 70,000 to 35,000 in the past three decades and was declared an endangered subspecies by the IUCN in 2019. The remaining number of Masai giraffe are geographically separated by the steep cliffs ... ...

    Abstract The Masai giraffe has experienced a population decline from 70,000 to 35,000 in the past three decades and was declared an endangered subspecies by the IUCN in 2019. The remaining number of Masai giraffe are geographically separated by the steep cliffs of the Gregory Rift escarpments (GRE) in Tanzania and Kenya dividing them into two populations, one west and one east of the GRE. The cliffs of the GRE are formidable barriers to east-west dispersal and gene flow and the few remaining natural corridors through the GRE are occupied by human settlements. To assess the impact of the GRE on Masai giraffe gene flow, we examined whole genome sequences of nuclear and mitochondrial DNA (mtDNA) variation in populations located east (Tarangire ecosystem) and west (Serengeti ecosystem) of the GRE in northern Tanzania. Evidence from mtDNA variation, which measures female-mediated gene flow, suggests that females have not migrated across the GRE between populations in the Serengeti and Tarangire ecosystems in the past ~289,000 years. The analysis of nuclear DNA variation compared to mtDNA DNA variation suggests that male-mediated gene flow across the GRE has occurred more recently but stopped a few thousand years ago. Our findings show that Masai giraffes are split into two populations and fulfill the criteria for designation as distinct evolutionary significant units (ESUs), which we denote as western Masai giraffe and eastern Masai giraffe. While establishing giraffe dispersal corridors across the GRE is impractical, conservation efforts should be focused on maintaining connectivity among populations within each of these two populations. The importance of these efforts is heightened by our finding that the inbreeding coefficients are high in some of these Masai giraffe populations, which could result in inbreeding depression in the small and fragmented populations.
    Language English
    Publishing date 2023-06-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2635675-2
    ISSN 2045-7758
    ISSN 2045-7758
    DOI 10.1002/ece3.10160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.

    Saraswat Ohri, Sujata / Forston, Michael D / Myers, Scott A / Brown, Brandon L / Andres, Kariena R / Howard, Russell M / Gao, Yonglin / Liu, Yu / Cavener, Douglas R / Hetman, Michal / Whittemore, Scott R

    Glia

    2024  

    Abstract: After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. ... ...

    Abstract After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI. We examined acute (<48 h post-SCI) and chronic (6 weeks post-SCI) effects of conditionally deleting Perk from OLs prior to SCI. While Perk transcript is expressed in many types of cells in the adult spinal cord, its levels are disproportionately high in OL lineage cells. Deletion of OL-Perk prior to SCI resulted in: (1) enhanced acute phosphorylation of eIF2α, a major PERK substrate and the critical mediator of the integrated stress response (ISR), (2) enhanced acute expression of the downstream ISR genes Atf4, Ddit3/Chop, and Tnfrsf10b/Dr5, (3) reduced acute OL lineage-specific Olig2 mRNA, but not neuronal or astrocytic mRNAs, (4) chronically decreased OL content in the spared white matter at the injury epicenter, (5) impaired hindlimb locomotor recovery, and (6) reduced chronic epicenter white matter sparing. Cultured primary OL precursor cells with reduced PERK expression and activated ER stress response showed: (1) unaffected phosphorylation of eIF2α, (2) enhanced ISR gene induction, and (3) increased cytotoxicity. Therefore, OL-Perk deficiency exacerbates ISR signaling and potentiates white matter damage after SCI. The latter effect is likely mediated by increased loss of Perk
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.24525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Masai giraffe population change over 40 years in Arusha National Park

    Lee, Derek E. / Lohay, George G. / Madeli, James / Cavener, Douglas R. / Bond, Monica L.

    African Journal of Ecology. 2023 June, v. 61, no. 2 p.345-353

    2023  

    Abstract: A population of Masai giraffes (Giraffa camelopardalis tippelskirchi) occurs in Arusha National Park (ANP), which is not part of the regular Tanzanian national wildlife monitoring scheme. Urban development of Arusha city and agricultural expansion have ... ...

    Abstract A population of Masai giraffes (Giraffa camelopardalis tippelskirchi) occurs in Arusha National Park (ANP), which is not part of the regular Tanzanian national wildlife monitoring scheme. Urban development of Arusha city and agricultural expansion have contributed to the increasing isolation of ANP from other protected areas in northern Tanzania. The only published data on the Masai giraffe population of ANP were individual‐based data collected in 1979 and 1980. Here, we used individual‐based data from 2021 to 2022 to provide an update on the current population size, population sex and age structure, movements and genetic connectivity of giraffes in ANP. We documented a 49% population decline and changes in the age distribution, adult sex ratio, reproductive rate and movement patterns relative to the previous study. Mitochondrial DNA analysis revealed genetic connectivity between ANP and other populations east of the Gregory Rift Escarpments in northern Tanzania and south‐eastern Kenya, evidence that Masai giraffe once moved widely across the landscape.
    Keywords Giraffa camelopardalis ; adults ; age structure ; landscapes ; mitochondrial DNA ; national parks ; population dynamics ; population size ; sex ratio ; urban development ; wildlife ; Kenya ; Tanzania
    Language English
    Dates of publication 2023-06
    Size p. 345-353.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 2019879-6
    ISSN 1365-2028 ; 0141-6707
    ISSN (online) 1365-2028
    ISSN 0141-6707
    DOI 10.1111/aje.13115
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Seeing spots: quantifying mother-offspring similarity and assessing fitness consequences of coat pattern traits in a wild population of giraffes (

    Lee, Derek E / Cavener, Douglas R / Bond, Monica L

    PeerJ

    2018  Volume 6, Page(s) e5690

    Abstract: Polymorphic phenotypes of mammalian coat coloration have been important to the study of genetics and evolution, but less is known about the inheritance and fitness consequences of individual variation in complex coat pattern traits such as spots and ... ...

    Abstract Polymorphic phenotypes of mammalian coat coloration have been important to the study of genetics and evolution, but less is known about the inheritance and fitness consequences of individual variation in complex coat pattern traits such as spots and stripes. Giraffe coat markings are highly complex and variable and it has been hypothesized that variation in coat patterns most likely affects fitness by camouflaging neonates against visually hunting predators. We quantified complex coat pattern traits of wild Masai giraffes using image analysis software, determined the similarity of spot pattern traits between mother and offspring, and assessed whether variation in spot pattern traits was related to fitness as measured by juvenile survival. The methods we described could comprise a framework for objective quantification of complex mammal coat pattern traits based on photographic coat pattern data. We demonstrated that some characteristics of giraffe coat spot shape were likely to be heritable, as measured by mother-offspring regression. We found significant variation in juvenile survival among phenotypic groups of neonates defined by multivariate clustering based on spot trait measurement variables. We also found significant variation in neonatal survival associated with spot size and shape covariates. Larger spots (smaller number of spots) and irregularly shaped or rounder spots (smaller aspect ratio) were correlated with increased survival. These findings will inform investigations into developmental and genetic architecture of complex mammal coat patterns and their adaptive value.
    Language English
    Publishing date 2018-10-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.5690
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Genetic connectivity and population structure of African savanna elephants (

    Lohay, George G / Weathers, Thomas Casey / Estes, Anna B / McGrath, Barbara C / Cavener, Douglas R

    Ecology and evolution

    2020  Volume 10, Issue 20, Page(s) 11069–11089

    Abstract: Increasing human population growth, exurban development, and associated habitat fragmentation is accelerating the isolation of many natural areas and wildlife populations across the planet. In Tanzania, rapid and ongoing habitat conversion to agriculture ...

    Abstract Increasing human population growth, exurban development, and associated habitat fragmentation is accelerating the isolation of many natural areas and wildlife populations across the planet. In Tanzania, rapid and ongoing habitat conversion to agriculture has severed many of the country's former wildlife corridors between protected areas. To identify historically linked protected areas, we investigated the genetic structure and gene flow of African savanna elephants in Tanzania using microsatellite and mitochondrial DNA markers in 688 individuals sampled in 2015 and 2017. Our results indicate distinct population genetic structure within and between ecosystems across Tanzania, and reveal important priority areas for connectivity conservation. In northern Tanzania, elephants sampled from the Tarangire-Manyara ecosystem appear marginally, yet significantly isolated from elephants sampled from the greater Serengeti ecosystem (mean
    Language English
    Publishing date 2020-10-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2635675-2
    ISSN 2045-7758
    ISSN 2045-7758
    DOI 10.1002/ece3.6728
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi.

    Ishengoma, Edson / Agaba, Morris / Cavener, Douglas R

    PeerJ

    2017  Volume 5, Page(s) e3145

    Abstract: Background: The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including ... ...

    Abstract Background: The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe's visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe's unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood.
    Methods: The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals.
    Results: Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in
    Discussion: By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptations. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. We hypothesize that requirement for long distance vision associated with predation and communication with conspecifics likely played an important role in the adaptive pressure on giraffe vision genes.
    Language English
    Publishing date 2017-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.3145
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Giraffe genome sequence reveals clues to its unique morphology and physiology

    Agaba, Morris / Ishengoma, Edson / Miller, Webb C. / McGrath, Barbara C. / Hudson, Chelsea N. / Bedoya Reina, Oscar C. / Ratan, Aakrosh / Burhans, Rico / Chikhi, Rayan / Medvedev, Paul / Praul, Craig A. / Wu-Cavener, Lan / Wood, Brendan / Robertson, Heather / Penfold, Linda / Cavener, Douglas R.

    Nature Communications

    2023  

    Keywords physiology ; morphology
    Publishing date 2023-03-10T14:34:19Z
    Publisher Springer
    Publishing country fr
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Sleeping Beauty, awake! Regulation of insulin gene expression by methylation of histone H3.

    Cavener, Douglas R

    Diabetes

    2008  Volume 58, Issue 1, Page(s) 28–29

    MeSH term(s) Animals ; Gene Expression Regulation/drug effects ; Glucose/pharmacology ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase ; Histones/metabolism ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/drug effects ; Islets of Langerhans/metabolism ; Methylation/drug effects ; Mice ; Models, Biological ; Protein Methyltransferases/genetics ; Protein Methyltransferases/metabolism ; Transcription, Genetic/drug effects
    Chemical Substances Histones ; Histone Methyltransferases (EC 2.1.1.-) ; Protein Methyltransferases (EC 2.1.1.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2008-12-29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db08-1520
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Co-opting regulation bypass repair as a gene-correction strategy for monogenic diseases.

    Hu, Jingjie / Bourne, Rebecca A / McGrath, Barbara C / Lin, Alice / Pei, Zifei / Cavener, Douglas R

    Molecular therapy : the journal of the American Society of Gene Therapy

    2021  Volume 29, Issue 11, Page(s) 3274–3292

    Abstract: With the development of CRISPR-Cas9-mediated gene-editing technologies, correction of disease-causing mutations has become possible. However, current gene-correction strategies preclude mutation repair in post-mitotic cells of human tissues, and a unique ...

    Abstract With the development of CRISPR-Cas9-mediated gene-editing technologies, correction of disease-causing mutations has become possible. However, current gene-correction strategies preclude mutation repair in post-mitotic cells of human tissues, and a unique repair strategy must be designed and tested for each and every mutation that may occur in a gene. We have developed a novel gene-correction strategy, co-opting regulation bypass repair (CRBR), which can repair a spectrum of mutations in mitotic or post-mitotic cells and tissues. CRBR utilizes the non-homologous end joining (NHEJ) pathway to insert a coding sequence (CDS) and transcription/translation terminators targeted upstream of any CDS mutation and downstream of the transcriptional promoter. CRBR results in simultaneous co-option of the endogenous regulatory region and bypass of the genetic defect. We validated the CRBR strategy for human gene therapy by rescuing a mouse model of Wolcott-Rallison syndrome (WRS) with permanent neonatal diabetes caused by either a large deletion or a nonsense mutation in the PERK (EIF2AK3) gene. Additionally, we integrated a CRBR GFP-terminator cassette downstream of the human insulin promoter in cadaver pancreatic islets of Langerhans, which resulted in insulin promoter regulated expression of GFP, demonstrating the potential utility of CRBR in human tissue gene repair.
    MeSH term(s) Animals ; CRISPR-Cas Systems ; Cell Line ; Female ; Gene Editing/methods ; Gene Expression ; Gene Knockdown Techniques ; Gene Order ; Gene Targeting ; Genes, Reporter ; Genetic Diseases, Inborn/genetics ; Genetic Diseases, Inborn/therapy ; Genetic Markers ; Genetic Therapy/methods ; Genetic Vectors/genetics ; Humans ; Male ; Mice ; Mutation ; RNA, Guide, CRISPR-Cas Systems ; eIF-2 Kinase/genetics
    Chemical Substances Genetic Markers ; RNA, Guide, CRISPR-Cas Systems ; EIF2AK3 protein, human (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1)
    Language English
    Publishing date 2021-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2021.04.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

    Edson Ishengoma / Morris Agaba / Douglas R. Cavener

    PeerJ, Vol 5, p e

    2017  Volume 3145

    Abstract: Background The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their ...

    Abstract Background The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe’s unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals. Results Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptations. At least some of ...
    Keywords Candidate vision genes ; Adaptive evolution ; Giraffe ; Okapi ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 590
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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