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Sample records for mole-rat heterocephalus glaber

  1. Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia

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    Philip G. Cox

    2014-06-01

    Full Text Available The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape–both important adaptations for a life dominated by digging with the incisors.

  2. Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber).

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    Sarko, Diana K; Leitch, Duncan B; Catania, Kenneth C

    2013-01-01

    The naked mole-rat (Heterocephalus glaber) is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats' behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors). These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

  3. Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber)

    DEFF Research Database (Denmark)

    Jørgensen, Kristine B.; Krogh-Jensen, Karen; Pickering, Darryl S

    2016-01-01

    The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1–5 of the naked mole-rat were compared to that of the house mouse (Mus...... musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies...

  4. Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae.

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    Matthew J Mason

    Full Text Available Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle. Heterocephalus deviates morphologically from the other bathyergids examined in that it has a more complex mastoid cavity structure, poorly-ossified processes of the malleus and incus, a 'columelliform' stapes and fewer cochlear turns. Bathyergids have semicircular canals with unusually wide diameters relative to their radii of curvature. How the lateral semicircular canal reaches the vestibule differs between species. Heterocephalus has much more limited high-frequency hearing than would be predicted from its small ear structures. The spongy bone forming its ossicular processes, the weak incudo-stapedial articulation, the columelliform stapes and (compared to other bathyergids reduced cochlear coiling are all potentially degenerate features which might reflect a lack of selective pressure on its peripheral auditory system. Substantial intraspecific differences were found in certain middle and inner ear structures, which might also result from relaxed selective pressures. However, such interpretations must be treated with caution in the absence of experimental evidence.

  5. Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae).

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    Mason, Matthew J; Cornwall, Hannah L; Smith, Ewan St J

    2016-01-01

    Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus) were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle. Heterocephalus deviates morphologically from the other bathyergids examined in that it has a more complex mastoid cavity structure, poorly-ossified processes of the malleus and incus, a 'columelliform' stapes and fewer cochlear turns. Bathyergids have semicircular canals with unusually wide diameters relative to their radii of curvature. How the lateral semicircular canal reaches the vestibule differs between species. Heterocephalus has much more limited high-frequency hearing than would be predicted from its small ear structures. The spongy bone forming its ossicular processes, the weak incudo-stapedial articulation, the columelliform stapes and (compared to other bathyergids) reduced cochlear coiling are all potentially degenerate features which might reflect a lack of selective pressure on its peripheral auditory system. Substantial intraspecific differences were found in certain middle and inner ear structures, which might also result from relaxed selective pressures. However, such interpretations must be treated with caution in the absence of experimental evidence.

  6. Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber

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    Diana K Sarko

    2013-11-01

    Full Text Available The naked mole-rat (Heterocephalus glaber is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats’ behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors. These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

  7. The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber)

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    Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K

    2014-01-01

    The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in ...

  8. Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

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    Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

    2014-04-01

    The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

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    Delaney, M A; Kinsel, M J; Treuting, P M

    2016-03-01

    The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

  10. Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Jørgensen, Kristine B; Krogh-Jensen, Karen; Pickering, Darryl S; Kanui, Titus I; Abelson, Klas S P

    2016-01-01

    The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.

  11. Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber).

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    Delaney, M A; Ward, J M; Walsh, T F; Chinnadurai, S K; Kerns, K; Kinsel, M J; Treuting, P M

    2016-05-01

    Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research. © The Author(s) 2016.

  12. Transcriptome sequencing of the naked mole rat (Heterocephalus glaber and identification of hypoxia tolerance genes

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    Bang Xiao

    2017-12-01

    Full Text Available The naked mole rat (NMR; Heterocephalus glaber is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression. In this study, we examined the sequence and transcript abundance data of the muscle transcriptome of NMRs exposed to hypoxia using the Illumina HiSeq 2500 system to clarify the possible genomic adaptive responses to the hypoxic underground surroundings. The RNA-seq raw FastQ data were mapped against the NMR genome. We identified 2337 differentially expressed genes (DEGs by comparison of the hypoxic and control groups. Functional annotation of the DEGs by gene ontology (GO analysis revealed enrichment of hypoxia stress-related GO categories, including ‘biological regulation’, ‘cellular process’, ‘ion transport’ and ‘cell-cell signaling’. Enrichment of DEGs in signaling pathways was analyzed against the Kyoto Encyclopedia of Genes and Genomes (KEGG database to identify possible interactions between DEGs. The results revealed significant enrichment of DEGs in focal adhesion, the mitogen-activated protein kinase (MAPK signaling pathway and the glycine, serine and threonine metabolism pathway. Furthermore, inhibition of DEGs (STMN1, MAPK8IP1 and MAPK10 expression induced apoptosis and arrested cell growth in NMR fibroblasts following hypoxia. Thus, this global transcriptome analysis of NMRs can provide an important genetic resource for the study of hypoxia tolerance in mammals. Furthermore, the identified DEGs may provide important molecular targets for biomedical research into therapeutic strategies for stroke and cardiovascular diseases.

  13. Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species.

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    Taylor, Kyle R; Milone, Nicholas A; Rodriguez, Carlos E

    2017-01-01

    The naked mole-rat (Heterocephalus glaber) is widely acclaimed to be cancer-resistant and of considerable research interest based on a paucity of reports of neoplasia in this species. We have, however, encountered four spontaneous cases of neoplasia and one presumptive case of neoplasia through routine necropsy and biopsy of individuals in a zoo collection of nonhybrid naked mole-rats bred from a single pair. One case each of metastasizing hepatocellular carcinoma, nephroblastoma (Wilms' tumor), and multicentric lymphosarcoma, as well as presumptive esophageal adenocarcinoma (Barrett's esophagus-like) was identified postmortem among 37 nonautolyzed necropsy submissions of naked mole-rats over 1-year-old that were submitted for necropsy between 1998 and August 2015. One incidental case of cutaneous hemangioma was also identified antemortem by skin biopsy from one naked mole-rat examined for trauma. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Challenging the inbreeding hypothesis in a eusocial mammal: population genetics of the naked mole-rat, Heterocephalus glaber.

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    Ingram, Colleen M; Troendle, Nicholas J; Gill, Clare A; Braude, Stanton; Honeycutt, Rodney L

    2015-10-01

    The role of genetic relatedness in the evolution of eusociality has been the topic of much debate, especially when contrasting eusocial insects with vertebrates displaying reproductive altruism. The naked mole-rat, Heterocephalus glaber, was the first described eusocial mammal. Although this discovery was based on an ecological constraints model of eusocial evolution, early genetic studies reported high levels of relatedness in naked mole-rats, providing a compelling argument that low dispersal rates and consanguineous mating (inbreeding as a mating system) are the driving forces for the evolution of this eusocial species. One caveat to accepting this long-held view is that the original genetic studies were based on limited sampling from the species' geographic distribution. A growing body of evidence supports a contrary view, with the original samples not representative of the species-rather reflecting a single founder event, establishing a small population south of the Athi River. Our study is the first to address these competing hypotheses by examining patterns of molecular variation in colonies sampled from north and south of the Athi and Tana rivers, which based on our results, serve to isolate genetically distinct populations of naked mole-rats. Although colonies south of the Athi River share a single mtDNA haplotype and are fixed at most microsatellite loci, populations north of the Athi River are considerably more variable. Our findings support the position that the low variation observed in naked mole-rat populations south of the Athi River reflects a founder event, rather than a consequence of this species' unusual mating system. © 2015 John Wiley & Sons Ltd.

  15. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber).

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    Liang, Sitai; Mele, James; Wu, Yuehong; Buffenstein, Rochelle; Hornsby, Peter J

    2010-08-01

    The naked mole-rat (NMR, Heterocephalus glaber) is a long-lived mammal in which spontaneous cancer has not been observed. To investigate possible mechanisms for cancer resistance in this species, we studied the properties of skin fibroblasts from the NMR following transduction with oncogenes that cause cells of other mammalian species to form malignant tumors. Naked mole-rat fibroblasts were transduced with a retrovirus encoding SV40 large T antigen and oncogenic Ras(G12V). Following transplantation of transduced cells into immunodeficient mice, cells rapidly entered crisis, as evidenced by the presence of anaphase bridges, giant cells with enlarged nuclei, multinucleated cells, and cells with large number of chromosomes or abnormal chromatin material. In contrast, similarly transduced mouse and rat fibroblasts formed tumors that grew rapidly without crisis. Crisis was also observed after > 40 population doublings in SV40 TAg/Ras-expressing NMR cells in culture. Crisis in culture was prevented by additional infection of the cells with a retrovirus encoding hTERT (telomerase reverse transcriptase). SV40 TAg/Ras/hTERT-expressing NMR cells formed tumors that grew rapidly in immunodeficient mice without evidence of crisis. Crisis could also be induced in SV40 TAg/Ras-expressing NMR cells by loss of anchorage, but after hTERT transduction, cells were able to proliferate normally following loss of anchorage. Thus, rapid crisis is a response of oncogene-expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth. The unique reaction of NMR cells to oncogene expression may form part of the cancer resistance of this species.

  16. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Park, Thomas J; Lu, Ying; Jüttner, René; Smith, Ewan St J; Hu, Jing; Brand, Antje; Wetzel, Christiane; Milenkovic, Nevena; Erdmann, Bettina; Heppenstall, Paul A; Laurito, Charles E; Wilson, Steven P; Lewin, Gary R

    2008-01-01

    In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  17. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Thomas J Park

    2008-01-01

    Full Text Available In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  18. Central visual system of the naked mole-rat (Heterocephalus glaber).

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    Crish, Samuel D; Dengler-Crish, Christine M; Catania, Kenneth C

    2006-02-01

    Naked mole-rats are fossorial rodents native to eastern Africa that spend their lives in extensive subterranean burrows where visual cues are poor. Not surprisingly, they have a degenerated eye and optic nerve, suggesting they have poor visual abilities. However, little is known about their central visual system. To investigate the organization of their central visual system, we injected a neuronal tracer into the eyes of naked mole-rats and mice to compare the neural structures mediating vision. We found that the superior colliculus and lateral geniculate nucleus were severely atrophied in the naked mole-rat. The olivary pretectal nucleus was reduced but still retained its characteristic morphology, possibly indicating a role in light detection. In addition, the suprachiasmatic nucleus is well innervated and resembles the same structure in other rodents. The naked mole-rat appears to have selectively lost structures that mediate form vision while retaining structures needed for minimal entrainment of circadian rhythms. Similar results have been reported for other mole-rat species. Taken together, these data suggest that light detection may still play an important role in the lives of these "blind" animals: most likely for circadian entrainment or setting seasonal rhythms.

  19. Multidimensional MRI-CT atlas of the naked mole-rat brain (Heterocephalus glaber).

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    Seki, Fumiko; Hikishima, Keigo; Nambu, Sanae; Okanoya, Kazuo; Okano, Hirotaka J; Sasaki, Erika; Miura, Kyoko; Okano, Hideyuki

    2013-01-01

    Naked mole-rats have a variety of distinctive features such as the organization of a hierarchical society (known as eusociality), extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI). Advanced MRI techniques such as diffusion tensor imaging (DTI), which generates high contrast images of fiber structures, can characterize unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D) images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualization of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

  20. Dominance and queen succession in captive colonies of the eusocial naked mole-rat, Heterocephalus glaber.

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    Clarke, F M; Faulkes, C G

    1997-07-22

    Naked mole-rat colonies exhibit a high reproductive skew, breeding being typically restricted to one female (the 'queen') and one to three males. Other colony members are reproductively suppressed, although this suppression can be reversed following the removal or death of the queen. We examined dominance and queen succession within captive colonies to investigate the relationship between urinary testosterone and cortisol, dominance rank and reproductive status; and to determine if behavioural and/or physiological parameters can be used as predictors of queen succession. Social structure was characterized by a linear dominance hierarchy before and after queen removal. Prior to queen removal, dominance rank was negatively correlated with body weight and urinary testosterone and cortisol titres in males and females. Queen removal results in social instability and aggression between high ranking individuals. Dominance rank appears to be a good predictor of reproductive status: queens are the highest ranking colony females and are succeeded by the next highest ranking females. The intense dominance-related aggression that accompanies reproductive succession in naked mole-rats provides empirical support for optimal skew theory.

  1. Social condition and oxytocin neuron number in the hypothalamus of naked mole-rats (Heterocephalus glaber).

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    Mooney, S J; Holmes, M M

    2013-01-29

    The naked mole-rat is a subterranean colonial rodent. In each colony, which can grow to as many as 300 individuals, there is only one female and 1-3 males that are reproductive and socially dominant. The remaining animals are reproductively suppressed subordinates that contribute to colony survival through their cooperative behaviors. Oxytocin is a peptide hormone that has shown relatively widespread effects on prosocial behaviors in other species. We examined whether social status affects the number of oxytocin-immunoreactive neurons in the paraventricular nucleus and the supraoptic nucleus by comparing dominant breeding animals to subordinate non-breeding workers from intact colonies. We also examined these regions in subordinate animals that had been removed from their colony and paired with an opposite- or same-sex conspecific for 6 months. Stereological analyses indicated that subordinates had significantly more oxytocin neurons in the paraventricular nucleus than breeders. Animals in both opposite- and same-sex pairs showed a decreased oxytocin neuron number compared to subordinates suggesting that status differences may be due to social condition rather than the reproductive activity of the animal per se. The effects of social status appear to be region specific as no group differences were found for oxytocin neuron number in the supraoptic nucleus. Given that subordinate naked mole-rats are kept reproductively suppressed through antagonism by the queen, we speculate that status differences are due either to oxytocin's anxiolytic properties to combat the stress of this antagonism or to its ability to promote the prosocial behaviors of subordinates. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K; Maloiy, Geoffrey M; Abelson, Klas S P

    2014-01-01

    The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.

  3. The long gestation of the small naked mole-rat (Heterocephalus glaber Rüppell, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography.

    Science.gov (United States)

    Roellig, Kathleen; Drews, Barbara; Goeritz, Frank; Hildebrandt, Thomas Bernd

    2011-03-07

    The naked mole-rat (Heterocephalus glaber) is one of the two known mammalian species that live in a eusocial population structure. Here we investigate the exceptionally long gestation period of 70 days observed in the mole-rat queen. The course of seven successful pregnancies in two individuals was recorded in a colony of captive naked mole-rats using ultrasound biomicroscopy (UBM) and 3D-ultrasonography. We establish a catalogue of basic reference ultrasound data for this species by describing the ultrasonographic appearance of reproductive organs, calculating growth curves to predict gestational age and defining ultrasonographic milestones to characterize pregnancy stages. Mean litter size was 10.9±2.7, of which 7.2±1.5 survived the weaning period. Mean interbirth interval was 128.8±63.0 days. The reproductive success in our colony did not differ from previously published data. In the queen the active corpora lutea had an anechoic, fluid filled centre. Using UBM, pregnancy could be detected 53 days before parturition. The period of embryonic development is assumed to last until 30 days before parturition. Embryonic resorptions were detected frequently in the queen, indicating that this might be an ordinary event in this species. We discuss the extraordinary long gestation period of this small rodent and postulate that the long gestation is beneficial to both the eusocial structure and longevity. An increased litter size, twice as large as for other rodents of similar size, seemingly compensates for the doubling of pregnancy length. We demonstrate that the lifetime reproductive effort of a naked mole-rat queen is equivalent to the mass of offspring that would be produced if all of the females of a colony would be reproducing.

  4. The long gestation of the small naked mole-rat (Heterocephalus glaber Ruppell, 1842 studied with ultrasound biomicroscopy and 3D-ultrasonography.

    Directory of Open Access Journals (Sweden)

    Kathleen Roellig

    Full Text Available The naked mole-rat (Heterocephalus glaber is one of the two known mammalian species that live in a eusocial population structure. Here we investigate the exceptionally long gestation period of 70 days observed in the mole-rat queen. The course of seven successful pregnancies in two individuals was recorded in a colony of captive naked mole-rats using ultrasound biomicroscopy (UBM and 3D-ultrasonography. We establish a catalogue of basic reference ultrasound data for this species by describing the ultrasonographic appearance of reproductive organs, calculating growth curves to predict gestational age and defining ultrasonographic milestones to characterize pregnancy stages. Mean litter size was 10.9±2.7, of which 7.2±1.5 survived the weaning period. Mean interbirth interval was 128.8±63.0 days. The reproductive success in our colony did not differ from previously published data. In the queen the active corpora lutea had an anechoic, fluid filled centre. Using UBM, pregnancy could be detected 53 days before parturition. The period of embryonic development is assumed to last until 30 days before parturition. Embryonic resorptions were detected frequently in the queen, indicating that this might be an ordinary event in this species. We discuss the extraordinary long gestation period of this small rodent and postulate that the long gestation is beneficial to both the eusocial structure and longevity. An increased litter size, twice as large as for other rodents of similar size, seemingly compensates for the doubling of pregnancy length. We demonstrate that the lifetime reproductive effort of a naked mole-rat queen is equivalent to the mass of offspring that would be produced if all of the females of a colony would be reproducing.

  5. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

    Science.gov (United States)

    Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

    2016-01-01

    Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  6. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Nikodemus Gessele

    Full Text Available Naked mole-rats (Heterocephalus glaber live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  7. Removal of reproductive suppression reveals latent sex differences in brain steroid hormone receptors in naked mole-rats, Heterocephalus glaber.

    Science.gov (United States)

    Swift-Gallant, Ashlyn; Mo, Kaiguo; Peragine, Deane E; Monks, D Ashley; Holmes, Melissa M

    2015-01-01

    Naked mole-rats are eusocial mammals, living in large colonies with a single breeding female and 1-3 breeding males. Breeders are socially dominant, and only the breeders exhibit traditional sex differences in circulating gonadal steroid hormones and reproductive behaviors. Non-reproductive subordinates also fail to show sex differences in overall body size, external genital morphology, and non-reproductive behaviors. However, subordinates can transition to breeding status if removed from their colony and housed with an opposite-sex conspecific, suggesting the presence of latent sex differences. Here, we assessed the expression of steroid hormone receptor and aromatase messenger RNA (mRNA) in the brains of males and females as they transitioned in social and reproductive status. We compared in-colony subordinates to opposite-sex subordinate pairs that were removed from their colony for either 1 day, 1 week, 1 month, or until they became breeders (i.e., produced a litter). Diencephalic tissue was collected and mRNA of androgen receptor (Ar), estrogen receptor alpha (Esr1), progesterone receptor (Pgr), and aromatase (Cyp19a1) was measured using qPCR. Testosterone, 17β-estradiol, and progesterone from serum were also measured. As early as 1 week post-removal, males exhibited increased diencephalic Ar mRNA and circulating testosterone, whereas females had increased Cyp19a1 mRNA in the diencephalon. At 1 month post-removal, females exhibited increased 17β-estradiol and progesterone. The largest changes in steroid hormone receptors were observed in breeders. Breeding females had a threefold increase in Cyp19a1 and fivefold increases in Esr1 and Pgr, whereas breeding males had reduced Pgr and increased Ar. These data demonstrate that sex differences in circulating gonadal steroids and hypothalamic gene expression emerge weeks to months after subordinate animals are removed from reproductive suppression in their home colony.

  8. Membrane phospholipid composition may contribute to exceptional longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun lipidomics.

    Science.gov (United States)

    Mitchell, Todd W; Buffenstein, Rochelle; Hulbert, A J

    2007-11-01

    Phospholipids containing highly polyunsaturated fatty acids are particularly prone to peroxidation and membrane composition may therefore influence longevity. Phospholipid molecules, in particular those containing docosahexaenoic acid (DHA), from the skeletal muscle, heart, liver and liver mitochondria were identified and quantified using mass-spectrometry shotgun lipidomics in two similar-sized rodents that show an approximately 9-fold difference in maximum lifespan. The naked mole rat is the longest-living rodent known with a maximum lifespan of >28 years. Total phospholipid distribution is similar in tissues of both species; DHA is only found in phosphatidylcholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS), and DHA is relatively more concentrated in PE than PC. Naked mole-rats have fewer molecular species of both PC and PE than do mice. DHA-containing phospholipids represent 27-57% of all phospholipids in mice but only 2-6% in naked mole-rats. Furthermore, while mice have small amounts of di-polyunsaturated PC and PE, these are lacking in naked mole-rats. Vinyl ether-linked phospholipids (plasmalogens) are higher in naked mole-rat tissues than in mice. The lower level of DHA-containing phospholipids suggests a lower susceptibility to peroxidative damage in membranes of naked mole-rats compared to mice. Whereas the high level of plasmalogens might enhance membrane antioxidant protection in naked mole-rats compared to mice. Both characteristics possibly contribute to the exceptional longevity of naked mole-rats and may indicate a special role for peroxisomes in this extended longevity.

  9. Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

    Science.gov (United States)

    Yosida, Shigeto; Okanoya, Kazuo

    2012-02-01

    Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

  10. Socially regulated reproductive development: analysis of GnRH-1 and kisspeptin neuronal systems in cooperatively breeding naked mole-rats (Heterocephalus glaber).

    Science.gov (United States)

    Zhou, Shuzhi; Holmes, Melissa M; Forger, Nancy G; Goldman, Bruce D; Lovern, Matthew B; Caraty, Alain; Kalló, Imre; Faulkes, Christopher G; Coen, Clive W

    2013-09-01

    In naked mole-rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH-1-ir cell bodies do not differ between gonad-intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH-1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlying puberty or seasonal breeding in other species. Copyright © 2013 Wiley Periodicals, Inc.

  11. The Naked Mole Rat Genome Resource : facilitating analyses of cancer and longevity-related adaptations

    OpenAIRE

    Keane, Michael; Craig, Thomas; Alfoldi, Jessica; Berlin, Aaron M; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M; de Magalhaes, Joao Pedro

    2014-01-01

    MOTIVATION: The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. RESULTS: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat's extraordinary traits, inc...

  12. Social status and sex effects on neural morphology in Damaraland mole-rats, Fukomys damarensis.

    Science.gov (United States)

    Anyan, Jeff J; Seney, Marianne L; Holley, Amanda; Bengston, Lynn; Goldman, Bruce D; Forger, Nancy G; Holmes, Melissa M

    2011-01-01

    We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf's nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew. 2011 S. Karger AG, Basel.

  13. Genome sequencing reveals insights into physiology and longevity of the naked mole rat

    DEFF Research Database (Denmark)

    Kim, Eun Bae; Fang, Xiaodong; Fushan, Alexey A

    2011-01-01

    The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age......-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized...... by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also...

  14. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations.

    Science.gov (United States)

    Keane, Michael; Craig, Thomas; Alföldi, Jessica; Berlin, Aaron M; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M; de Magalhães, João Pedro

    2014-12-15

    The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat's extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource (http://www.naked-mole-rat.org), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species. © The Author 2014. Published by Oxford University Press.

  15. Genome Stability Maintenance in Naked Mole-Rat.

    Science.gov (United States)

    Petruseva, I O; Evdokimov, A N; Lavrik, O I

    2017-01-01

    The naked mole-rat ( Heterocephalus glaber ) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest lived rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance. Despite the fact that the naked mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main characteristics of its genome and proteome are a high stability and effective functioning. Replicative senescence in the somatic cells of naked mole-rats is missing, while an additional p53/pRb-dependent mechanism of early contact inhibition has been revealed in its fibroblasts, which controls cell proliferation and its mechanism of arf- dependent aging. The unique traits of phenotypic and molecular adaptations found in the naked mole-rat speak to a high stability and effective functioning of the molecular machinery that counteract damage accumulation in its genome. This review analyzes existing results in the study of the molecular basis of longevity and high cancer resistance in naked mole-rats.

  16. Naked mole-rat cortical neurons are resistant to acid-induced cell death

    OpenAIRE

    Husson, Zoé; Smith, Ewan S

    2018-01-01

    Abstract Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+ permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are ...

  17. Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat.

    Science.gov (United States)

    Park, Thomas J; Reznick, Jane; Peterson, Bethany L; Blass, Gregory; Omerbašić, Damir; Bennett, Nigel C; Kuich, P Henning J L; Zasada, Christin; Browe, Brigitte M; Hamann, Wiebke; Applegate, Daniel T; Radke, Michael H; Kosten, Tetiana; Lutermann, Heike; Gavaghan, Victoria; Eigenbrod, Ole; Bégay, Valérie; Amoroso, Vince G; Govind, Vidya; Minshall, Richard D; Smith, Ewan St J; Larson, John; Gotthardt, Michael; Kempa, Stefan; Lewin, Gary R

    2017-04-21

    The African naked mole-rat's ( Heterocephalus glaber ) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease. Copyright © 2017, American Association for the Advancement of Science.

  18. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    Directory of Open Access Journals (Sweden)

    Irmgard eAmrein

    2014-05-01

    Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

  19. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

    Science.gov (United States)

    Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

  20. Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

    OpenAIRE

    Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase act...

  1. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-07-18

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

  2. The molecular basis of acid insensitivity in the African naked mole-rat.

    Science.gov (United States)

    Smith, Ewan St John; Omerbašić, Damir; Lechner, Stefan G; Anirudhan, Gireesh; Lapatsina, Liudmila; Lewin, Gary R

    2011-12-16

    Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.

  3. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

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    Yu, Chuanfei; Li, Yang; Holmes, Andrew; Szafranski, Karol; Faulkes, Chris G; Coen, Clive W; Buffenstein, Rochelle; Platzer, Matthias; de Magalhães, João Pedro; Church, George M

    2011-01-01

    The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  4. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

    Directory of Open Access Journals (Sweden)

    Chuanfei Yu

    Full Text Available The naked mole-rat (Heterocephalus glaber is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam, a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m, and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  5. Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors.

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    Faulkes, Chris G; Bennett, Nigel C

    2013-05-19

    Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (Heterocephalus glaber and Fukomys damarensis). The common mole-rat (Cryptomys hottentotus) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.

  6. Morphological divergence of breeders and helpers in wild Damaraland mole-rat societies.

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    Young, Andrew J; Bennett, Nigel C

    2010-11-01

    The specialization of body shape to an individual's role within society represents a pinnacle of social evolution. Although commonplace among social insects, divergence in the body shapes of breeders and helpers has to date been documented in just one social vertebrate, the naked mole-rat, Heterocephalus glaber; an extraordinary species in which large colony size and frequent inbreeding may have favored the evolution of such specialization. Here, we present new evidence of morphological divergence between breeders and helpers in the Damaraland mole-rat, Fukomys damarensis; a much less socially extreme species that reflects an independent evolutionary origin of sociality. Using longitudinal data from wild populations, we show that dominant female Damaraland mole-rats, like many social insect queens, have a significantly more elongate body shape than subordinates. This difference arises not from a pre-existing difference in the body shapes of subordinates that do, and those that do not, become dominant, but from a modification to the growth trajectory of subordinates on dominance acquisition. Our findings reveal a wider role for morphological divergence within vertebrate societies and, as Damaraland mole-rats neither live in unusually large groups nor inbreed, suggest that circumstances favoring the evolution of such specializations may be more widespread among vertebrates than previously supposed. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

  7. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.

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    Azpurua, Jorge; Ke, Zhonghe; Chen, Iris X; Zhang, Quanwei; Ermolenko, Dmitri N; Zhang, Zhengdong D; Gorbunova, Vera; Seluanov, Andrei

    2013-10-22

    The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

  8. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.

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    Smith, Ewan St John; Blass, Gregory R C; Lewin, Gary R; Park, Thomas J

    2010-05-24

    Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

  9. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

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    Lewin Gary R

    2010-05-01

    Full Text Available Abstract Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

  10. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

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    Gorbunova, Vera; Hine, Christopher; Tian, Xiao; Ablaeva, Julia; Gudkov, Andrei V.; Nevo, Eviatar; Seluanov, Andrei

    2012-01-01

    Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground. PMID:23129611

  11. Sex, social status, and CRF receptor densities in naked mole-rats.

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    Beery, Annaliese K; Bicks, Lucy; Mooney, Skyler J; Goodwin, Nastacia L; Holmes, Melissa M

    2016-02-01

    Naked mole-rats (Heterocephalus glaber) live in groups that are notable for their large size and caste structure, with breeding monopolized by a single female and a small number of males. Recent studies have demonstrated substantial differences between the brains of breeders and subordinates induced by changes in social standing. Corticotropin-releasing factor (CRF) receptors-which bind the hormone CRF as well as related peptides-are important regulators of stress and anxiety, and are emerging as factors affecting social behavior. We conducted autoradiographic analyses of CRF1 and CRF2 receptor binding densities in female and male naked mole-rats varying in breeding status. Both globally and in specific brain regions, CRF1 receptor densities varied with breeding status. CRF1 receptor densities were higher in subordinates across brain regions, and particularly in the piriform cortex and cortical amygdala. Sex differences were present in CRF2 receptor binding densities, as is the case in multiple vole species. CRF2 receptor densities were higher in females, both globally and in the cortical amygdala and lateral amygdalar nucleus. These results provide novel insights into the neurobiology of social hierarchy in naked mole-rats, and add to a growing body of work that links changes in the CRF system with social behavior. © 2015 Wiley Periodicals, Inc.

  12. Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age

    Science.gov (United States)

    Ruby, J Graham; Smith, Megan

    2018-01-01

    The longest-lived rodent, the naked mole-rat (Heterocephalus glaber), has a reported maximum lifespan of >30 years and exhibits delayed and/or attenuated age-associated physiological declines. We questioned whether these mouse-sized, eusocial rodents conform to Gompertzian mortality laws by experiencing an exponentially increasing risk of death as they get older. We compiled and analyzed a large compendium of historical naked mole-rat lifespan data with >3000 data points. Kaplan-Meier analyses revealed a substantial portion of the population to have survived at 30 years of age. Moreover, unlike all other mammals studied to date, and regardless of sex or breeding-status, the age-specific hazard of mortality did not increase with age, even at ages 25-fold past their time to reproductive maturity. This absence of hazard increase with age, in defiance of Gompertz’s law, uniquely identifies the naked mole-rat as a non-aging mammal, confirming its status as an exceptional model for biogerontology. PMID:29364116

  13. Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age.

    Science.gov (United States)

    Stoll, Elizabeth A; Karapavlovic, Nevena; Rosa, Hannah; Woodmass, Michael; Rygiel, Karolina; White, Kathryn; Turnbull, Douglass M; Faulkes, Chris G

    2016-12-19

    The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades.

  14. Sperm structure and motility in the eusocial naked mole-rat, Heterocephalus glaber: a case of degenerative orthogenesis in the absence of sperm competition?

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    van der Horst Gerhard

    2011-12-01

    Full Text Available Abstract Background We have studied sperm structure and motility in a eusocial rodent where reproduction is typically restricted to a single male and behaviourally dominant queen. Males rarely compete for access to the queen during her estrus cycle, suggesting little or no role for sperm competition. Results Our results revealed an atypical mammalian sperm structure with spermatozoa from breeding, subordinate and disperser males being degenerate and almost completely lacking a "mammalian phylogenetic stamp". Sperm structure is characterized by extreme polymorphism with most spermatozoa classified as abnormal. Sperm head shapes include round, oval, elongated, lobed, asymmetrical and amorphous. At the ultrastructural level, the sperm head contains condensed to granular chromatin with large open spaces between the chromatin. Nuclear chromatin seems disorganized since chromatin condensation is irregular and extremely inconsistent. The acrosome forms a cap (ca 35% over the anterior part of the head. A well defined nuclear fossa and neck with five minor sets of banded protein structures are present. The midpiece is poorly organized and contains only 5 to 7 round to oval mitochondria. The flagellar pattern is 9+9+2. A distinct degenerative feature of the tail principal piece is the absence of the fibrous sheath. Only 7% motile spermatozoa were observed which had exceptionally slow swimming speeds. Conclusion In this species, sperm form has simplified and degenerated in many aspects and represents a specialised form of degenerative orthogenesis at the cellular level.

  15. Endocrine function and neurobiology of the longest-living rodent, the naked mole-rat.

    Science.gov (United States)

    Edrey, Yael H; Park, Thomas J; Kang, Hyesin; Biney, Adriana; Buffenstein, Rochelle

    2011-01-01

    Animals that have evolved exceptional capabilities, such as extraordinary longevity may reveal pertinent and potentially critical insights into biomedical research that are not readily apparent in standard laboratory animals. Naked mole-rats (Heterocephalus glaber; NMRs) are extremely long-lived (30 years) mouse-sized rodents. They clearly have evolved superior anti-aging mechanisms as evident by the markedly attenuated age-related decline in physiological function, sustained reproductive capacity and pronounced cancer resistance throughout their long-lives. These eusocial rodents, like the social insects, live in colonies with breeding restricted to one female and a few males. Subordinates are sexually monomorphic, yet retain the ability to become breeders, and can undergo growth surges and neural modifications at any time throughout their life. This plasticity in physiological and behavioral aspects may have contributed to their long-lives. Naked mole-rats show numerous adaptations to life underground including extreme tolerance of hypoxia, acid insensitivity, as well as independence of photoendocrine systems. Here we review what is known about their unique social structure, sensory systems, endocrinology and neurobiology, and highlight areas that may be pertinent to biogerontology. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

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    Rodriguez, Karl A; Edrey, Yael H; Osmulski, Pawel; Gaczynska, Maria; Buffenstein, Rochelle

    2012-01-01

    The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

  17. Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

    Science.gov (United States)

    St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

    2012-08-15

    In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

  18. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

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    Karl A Rodriguez

    Full Text Available The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber, maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L activity and a two-fold increase in trypsin-like (T-L in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

  19. A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence.

    Science.gov (United States)

    Lewis, Kaitlyn N; Rubinstein, Nimrod D; Buffenstein, Rochelle

    2018-04-20

    Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives.

  20. Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain.

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    Holmes, Melissa M; Goldman, Bruce D; Forger, Nancy G

    2008-08-01

    Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.

  1. Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

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    Xiaodong Fang

    2014-09-01

    Full Text Available Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber. Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.

  2. Subcaste differences in neural activation suggest a prosocial role for oxytocin in eusocial naked mole-rats.

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    Hathaway, Georgia A; Faykoo-Martinez, Mariela; Peragine, Deane E; Mooney, Skyler J; Holmes, Melissa M

    2016-03-01

    The neuropeptide oxytocin (OT) influences prosocial behavior(s), aggression, and stress responsiveness, and these diverse effects are regulated in a species- and context-specific manner. The naked mole-rat (Heterocephalus glaber) is a unique species with which to study context-dependent effects of OT, exhibiting a strict social hierarchy with behavioral specialization within the subordinate caste: soldiers are aggressive and defend colonies against unfamiliar conspecifics while workers are prosocial and contribute to in-colony behaviors such as pup care. To determine if OT is involved in subcaste-specific behaviors, we compared behavioral responses between workers and soldiers of both sexes during a modified resident/intruder paradigm, and quantified activation of OT neurons in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) using the immediate-early-gene marker c-fos co-localized with OT neurons. Resident workers and soldiers were age-matched with unfamiliar worker stimulus animals as intruders, and encounters were videorecorded and scored for aggressive behaviors. Colony-matched controls were left in their home colony for the duration of the encounters. Brains were extracted and cell counts were conducted for OT immunoreactive (ir), c-fos-ir, and percentage of OT-c-fos double-labeled cells. Results indicate that resident workers were less aggressive but showed greater OT neural activity than soldiers. Furthermore, a linear model including social treatment, cortisol, and subcaste revealed that subcaste was the only significant predictor of OT-c-fos double-labeled cells in the PVN. These data suggest that in naked mole-rats OT promotes prosocial behaviors rather than aggression and that even within subordinates status exerts robust effects on brain and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A distinct role of the queen in coordinated workload and soil distribution in eusocial naked mole-rats.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Kutsukake

    Full Text Available We investigated how group members achieve collective decision-making, by considering individual intrinsic behavioural rules and behavioural mechanisms for maintaining social integration. Using a simulated burrow environment, we investigated the behavioural rules of coordinated workload for soil distribution in a eusocial mammal, the naked mole-rat (Heterocephalus glaber. We tested two predictions regarding a distinct role of the queen, a socially dominant individual in the caste system: the presence of a queen would increase the workload of other caste individuals, and the cues by a queen would affect the soil distribution. In experiment 1, we placed four individuals of various castes from the same colony into an experimental burrow. Workers exhibited the highest frequency of workload compared to other castes. The presence of a queen activated the workload by other individuals. Individuals showed a consistent workload in a particular direction so as to bias the soil distribution. These results suggest that individuals have a consensus on soil distribution and that the queen plays a distinct role. In experiment 2, we placed the odour of a queen in one of four cells and observed its effect on other individuals' workload and soil distribution. Relative to other cells, individuals frequently dug in the queen cell so the amount of soil in the queen cell decreased. These results suggest that queen odour is an important cue in coordinated workload and soil distribution in this species.

  4. The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

    Directory of Open Access Journals (Sweden)

    Malene Brohus

    Full Text Available Naked mole-rats (Heterocephalus glaber (NMRs are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs, and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A, shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

  5. The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

    Science.gov (United States)

    Brohus, Malene; Gorbunova, Vera; Faulkes, Chris G; Overgaard, Michael T; Conover, Cheryl A

    2015-01-01

    Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

  6. Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

    Science.gov (United States)

    Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with 75Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

  7. Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

    Directory of Open Access Journals (Sweden)

    Jie Pan

    Full Text Available The pulmonary neuroepithelial bodies (NEBs constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+ via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT, and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR, Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates. The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1 NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2 NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3 NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4 NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA and the neurogenic gene (MASH1 indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional

  8. Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

    Science.gov (United States)

    Pan, Jie; Park, Thomas J; Cutz, Ernest; Yeger, Herman

    2014-01-01

    The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and

  9. Theoretical paper: exploring overlooked natural mitochondria-rejuvenative intervention: the puzzle of bowhead whales and naked mole rats.

    Science.gov (United States)

    Prokopov, Arkadi F

    2007-12-01

    There is an imperative need for exploring and implementing mitochondria-rejuvenative interventions that can bridge the current gap toward the step-by step realization of strategies for engineered negligible senescence (SENS) agenda. Recently discovered in mammals, natural mechanism mitoptosis-a selective "suicide" of mutated mitochondria-can facilitate continuous purification of mitochondrial pool in an organism from the most reactive oxygen species (ROS)-producing mitochondria. Mitoptosis, which is considered to be the first stage of ROS-induced apoptosis, underlies follicular atresia (a "quality control" mechanism in female germline cells that eliminates most germinal follicles in female embryos). Mitoptosis can be also activated in adult postmitotic somatic cells by evolutionary conserved phenotypic adaptations to intermittent oxygen restriction (IOR) and synergistically acting intermittent caloric restriction (ICR). IOR and ICR are common in mammals and seem to underlie extraordinary longevity and augmented cancer resistance in bowhead whales (Balena mysticetus) and naked mole rats (Heterocephalus glaber). Furthermore, in mammals IOR can facilitate continuous stromal stem cells-de-pendent tissue repair. A comparative analysis of IOR and ICR mechanisms in both mammals, in conjunction with the experience of decades of biomedical and clinical research on emerging preventative, therapeutic, and rehabilitative modality-the intermittent hypoxic training/therapy (IHT)-indicates that the notable clinical efficiency of IHT is based on the universal adaptational mechanisms that are common in mammals. Further exploration of natural mitochondria-preserving and -rejuvenating strategies can help refinement of IOR- and ICR-based synergistic protocols, having value in clinical human rejuvenation.

  10. H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole-rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Zhao, Shanmin; Li, Li; Wang, Shiyong; Yu, Chenlin; Xiao, Bang; Lin, Lifang; Cong, Wei; Cheng, Jishuai; Yang, Wenjing; Sun, Wei; Cui, Shufang

    2016-12-20

    Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308. By contrast, CQ treatment decreased p70S6K, AktSer473, and AktThr308 levels. The Bax/Bcl-2 ratio increased after 12 h of exposure to LY294002 or CQ. These data show that inhibiting the Akt pathway promotes autophagy and apoptosis in NMR skin fibroblasts. Furthermore, LY294002 or CQ treatment decreased caspase-3, p53, and HIF1-α levels, suggesting that serum starvation or H2O2 treatment increase autophagy and apoptosis in NMR skin fibroblasts by inhibiting the PI3K/Akt pathway. CQ-induced inhibition of late autophagy stages also prevented Akt activation and induced apoptosis. Finally, the HIF-1α and p53 pathways were involved in serum starvation- or H2O2-induced autophagy in NMR skin fibroblasts.

  11. Social structure predicts genital morphology in African mole-rats.

    Directory of Open Access Journals (Sweden)

    Marianne L Seney

    2009-10-01

    Full Text Available African mole-rats (Bathyergidae, Rodentia exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure.We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate.The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  12. Social structure predicts genital morphology in African mole-rats.

    Science.gov (United States)

    Seney, Marianne L; Kelly, Diane A; Goldman, Bruce D; Sumbera, Radim; Forger, Nancy G

    2009-10-15

    African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  13. Extreme hypoxia tolerance of naked mole-rat brain.

    Science.gov (United States)

    Larson, John; Park, Thomas J

    2009-12-09

    Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

  14. Burrow architecture of the Damaraland mole-rat ( Fukomys ...

    African Journals Online (AJOL)

    The burrow architecture (length, internal dimensions, fractal dimension of tunnel systems, number of nesting chambers and surface mounds) was investigated in the Damaraland mole-rat (Fukomys damarensis). A total of 31 animals were caught from five different colonies and their burrow systems were excavated in their ...

  15. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    OpenAIRE

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years 1–3 . This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years 4,5 . In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single inci...

  16. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years1–3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4,5. In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2,6. Here we identify a mechanism responsible for the naked mole-rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high molecular weight hyaluronan (HA), which is over five times larger than human or mouse HA. This high molecular weight HA accumulates abundantly in naked mole rat tissues due to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as the naked mole rat cells have a higher affinity to HA than the mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become susceptible to malignant transformation and readily form tumors in mice. We speculate that naked mole-rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. PMID:23783513

  17. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Sleep in the Cape Mole Rat: A Short-Sleeping Subterranean Rodent.

    Science.gov (United States)

    Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R

    2016-01-01

    The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.

  19. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Azpurua, Jorge; Feigenson, Marina; Bozzella, Michael; Mao, Zhiyong; Catania, Kenneth C; Gorbunova, Vera

    2009-11-17

    The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.

  20. Assessment of naked mole-rat distribution and threats in Eastern Ethiopia

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    Mengistu Wale

    2016-08-01

    Full Text Available Objective: To identify the distribution, threats and community attitudes towards naked molerat in Eastern Ethiopia. Methods: Data were collected through direct observation and interview and Chi-square at 95% confidence interval was used for significance test. Results: Naked mole-rat was identified in Fafan, City/Shinele, Eastern Hararghe Zone and Dire Dawa Administrative. The main threats of naked mole-rat identified were agricultural expansion, human killing and lack of awareness. From a total of 100 respondents, 92% of them considered naked mole-rat as pest as a result that 46% of them participated in direct killing. Literacy rate significantly affects the willingness to participate in the conservation of naked mole-rat (χ2 = 7.478, df = 1, P < 0.05. From a total of 26% respondents who did not show the willingness to participate in the conservation, 80.8% of them were illiterate. Conclusions: Naked mole-rat is fairly common in many of the study sites. However, rapid shift from nomadic life style to cultivation of crops and lacks of awareness were the main threats of naked mole-rat. Therefore, since there is no conservation action currently, further comprehensive study is required to design conservation plan for this species.

  1. High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

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    Shanmin Zhao

    2014-02-01

    Full Text Available Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old and adult C57BL/6 mice (eight weeks old have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

  2. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

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    Bethany L Peterson

    Full Text Available Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6 and older (postnatal day 20 age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  3. The naked mole-rat response to oxidative stress: just deal with it.

    Science.gov (United States)

    Lewis, Kaitlyn N; Andziak, Blazej; Yang, Ting; Buffenstein, Rochelle

    2013-10-20

    The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.

  4. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

    Science.gov (United States)

    Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

    2012-01-01

    Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  5. Unraveling the message: insights into comparative genomics of the naked mole-rat.

    Science.gov (United States)

    Lewis, Kaitlyn N; Soifer, Ilya; Melamud, Eugene; Roy, Margaret; McIsaac, R Scott; Hibbs, Matthew; Buffenstein, Rochelle

    2016-08-01

    Animals have evolved to survive, and even thrive, in different environments. Genetic adaptations may have indirectly created phenotypes that also resulted in a longer lifespan. One example of this phenomenon is the preternaturally long-lived naked mole-rat. This strictly subterranean rodent tolerates hypoxia, hypercapnia, and soil-based toxins. Naked mole-rats also exhibit pronounced resistance to cancer and an attenuated decline of many physiological characteristics that often decline as mammals age. Elucidating mechanisms that give rise to their unique phenotypes will lead to better understanding of subterranean ecophysiology and biology of aging. Comparative genomics could be a useful tool in this regard. Since the publication of a naked mole-rat genome assembly in 2011, analyses of genomic and transcriptomic data have enabled a clearer understanding of mole-rat evolutionary history and suggested molecular pathways (e.g., NRF2-signaling activation and DNA damage repair mechanisms) that may explain the extraordinarily longevity and unique health traits of this species. However, careful scrutiny and re-analysis suggest that some identified features result from incorrect or imprecise annotation and assembly of the naked mole-rat genome: in addition, some of these conclusions (e.g., genes involved in cancer resistance and hairlessness) are rejected when the analysis includes additional, more closely related species. We describe how the combination of better study design, improved genomic sequencing techniques, and new bioinformatic and data analytical tools will improve comparative genomics and ultimately bridge the gap between traditional model and nonmodel organisms.

  6. Extended longevity of reproductives appears to be common in Fukomys mole-rats (Rodentia, Bathyergidae.

    Directory of Open Access Journals (Sweden)

    Philip Dammann

    Full Text Available African mole-rats (Bathyergidae, Rodentia contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive "helpers" in their natal families, often for several years. This "reproductive subdivision" of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli, breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5-2.2fold depending on the sex, irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats.

  7. Stress Resistance in the Naked Mole-Rat: The Bare Essentials – A Mini-Review

    Science.gov (United States)

    Lewis, Kaitlyn N.; Mele, James; Hornsby, Peter J.; Buffenstein, Rochelle

    2012-01-01

    Background Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ∼8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. Objectives We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Results Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD50 values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Conclusion Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and

  8. Stress resistance in the naked mole-rat: the bare essentials - a mini-review.

    Science.gov (United States)

    Lewis, Kaitlyn N; Mele, James; Hornsby, Peter J; Buffenstein, Rochelle

    2012-01-01

    Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ~8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD(50) values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and progression of physiological declines

  9. Influence of spatial environment on maze learning in an African mole-rat

    CSIR Research Space (South Africa)

    Du Toit, L

    2012-05-01

    Full Text Available -1 Anim Cogn DOI 10.1007/s10071-012-0503-0 Influence of spatial environment on maze learning in an African mole-rat Lydia du Toit ? Nigel C. Bennett ? Alecia Nickless ? Martin J. Whiting L. du Toit , A. Nickless , M. J. Whiting (email) School...

  10. The eye of the African mole-rat Cryptomys anselli : to see or not to see?

    NARCIS (Netherlands)

    Cernuda-Cernuda, R; Garcia-Fernandez, JM; Gordijn, MCM; Bovee-Geurts, PHM; DeGrip, WJ; de Grip, W.J.

    In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located

  11. The eye of the african mole-rat Cryptomys anselli: to see or not to see?

    NARCIS (Netherlands)

    Cernuda-Cernuda, R.; Garcia-Fernandez, J.M.; Gordijn, M.C.; Bovee-Geurts, P.H.M.; Grip, W.J. de

    2003-01-01

    In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located

  12. The reproductive biology of the giant Zambian mole-rat, Cryptomys ...

    African Journals Online (AJOL)

    1994-09-29

    Sep 29, 1994 ... gala (12° 27'S, 2T51'E) in the Copperbelt of northern Zam- hia. ... mole-rat, a pair of animals and a group comprising one male and three females .... Figure 1 Changes In bouy mass of a captive female Cr.vptom.vs mechowi ... The sex distribution was .... 'Ine social Cryptomys species are chmacteril,ed hy.

  13. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

    NARCIS (Netherlands)

    S.L. Macrae (Sheila L.); Q. Zhang (Quanwei); C. Lemetre (Christophe); I. Seim (Inge); R.B. Calder (Robert B.); J.H.J. Hoeijmakers (Jan); Y. Suh (Yousin); V.N. Gladyshev (Vadim N.); A. Seluanov (Andrei); V. Gorbunova (Vera); J. Vijg (Jan); Z.D. Zhang (Zhengdong D.)

    2015-01-01

    textabstractGenome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM

  14. Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

    Science.gov (United States)

    LaVinka, Pamela Colleen; Park, Thomas J

    2012-01-01

    Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%), and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%), naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2).

  15. Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Pamela Colleen LaVinka

    Full Text Available Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%, and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%, naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2.

  16. Distribution of vasopressin in the brain of the eusocial naked mole-rat.

    Science.gov (United States)

    Rosen, Greta J; De Vries, Geert J; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

    2007-02-20

    Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.

  17. Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats.

    Science.gov (United States)

    Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C

    2015-11-01

    Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

  18. Locomotor Activity and Body Temperature Patterns over a Temperature Gradient in the Highveld Mole-Rat (Cryptomys hottentotus pretoriae).

    Science.gov (United States)

    Haupt, Meghan; Bennett, Nigel C; Oosthuizen, Maria K

    2017-01-01

    African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation. Here we test the effect of ambient temperature on locomotor activity and body temperature, and the relationship between the two parameters, in the highveld mole-rat. We exposed mole-rats to a 12L:12D and a DD light cycle at ambient temperatures of 30°C, 25°C and 20°C while locomotor activity and body temperature were measured simultaneously. In addition, we investigated the endogenous rhythms of locomotor activity and body temperature at different ambient temperatures. Mole-rats displayed nocturnal activity at all three ambient temperatures and were most active at 20°C, but least active at 30°C. Body temperature was highest at 30°C and lowest at 20°C, and the daily cycle was highly correlated with locomotor activity. We show that the mole-rats have endogenous rhythms for both locomotor activity and body temperature. However, the endogenous body temperature rhythm appears to be less robust compared to the locomotor activity rhythm. Female mole-rats appear to be more sensitive to temperature changes than males, increased heterothermy is evident at lower ambient temperatures, whilst males show smaller variation in their body temperatures with changing ambient temperatures. Mole-rats may rely more heavily on behavioural thermoregulation as it is more energy efficient in an already challenging environment.

  19. O2 binding and CO2 sensitivity in haemoglobins of subterranean African mole rats

    DEFF Research Database (Denmark)

    Weber, Roy E.; Jarvis, Jennifer U. M.; Fago, Angela

    2017-01-01

    that predictably safeguard pulmonary loading under hypoxic and hypercapnic burrow conditions. The O2 binding characteristics are discussed in relation to available information on the primary structure of Hbs from adult and developmental stages of mammals subjected to hypoxia and hypercapnia and the molecular......Inhabiting deep and sealed subterranean burrows, mole rats exhibit a remarkable suite of specializations, including eusociality (living in colonies with single breeding queens), extraordinary longevity, cancer immunity and poikilothermy, and extreme tolerance of hypoxia and hypercapnia. With little...... and 2,3-diphosphoglycerate (DPG, the major allosteric modulator of Hb-O2 affinity in red blood cells) in four social and two solitary species of African mole rats (family Bathyergidae) originating from different biomes and soil types across Central and Southern Africa. We found no consistent patterns...

  20. Effects of ultraviolet radiation on mole rats kidney: A histopathologic and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Hüseyin Türker

    2014-04-01

    Full Text Available The purpose of this study was to realize the ultrastructural effects of ultraviolet radiation on the kidney tissue cells of mole rats (Spalax leucodon. The mole rats of 180–200 g body weight were divided into the control and radiation-trial groups. The control group was not given any radiation. The other groups were irradiated with artificially produced UVC radiation for 14, 28 and 60 days. The kidney tissue samples were prepared at the end of experiments and analyzed by the light and electron microscope. Several effects were observed in the kidney tissues cells analyzed in accordance with the dose magnitude of radiation. These results clearly show the detrimental effects of UVC radiation on kidney tissue cells in exposure periods dependent on radiation dose and exposure time.

  1. Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

    Science.gov (United States)

    Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

    2015-12-01

    During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

    Science.gov (United States)

    Omerbašić, Damir; Smith, Ewan St J; Moroni, Mirko; Homfeld, Johanna; Eigenbrod, Ole; Bennett, Nigel C; Reznick, Jane; Faulkes, Chris G; Selbach, Matthias; Lewin, Gary R

    2016-10-11

    The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat

    Directory of Open Access Journals (Sweden)

    Damir Omerbašić

    2016-10-01

    Full Text Available The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF, an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.

  4. Genetic signatures for enhanced olfaction in the African mole-rats.

    Directory of Open Access Journals (Sweden)

    Sofia Stathopoulos

    Full Text Available The Olfactory Receptor (OR superfamily, the largest in the vertebrate genome, is responsible for vertebrate olfaction and is traditionally subdivided into 17 OR families. Recent studies characterising whole-OR subgenomes revealed a 'birth and death' model of evolution for a range of species, however little is known about fine-scale evolutionary dynamics within single-OR families. This study reports the first assessment of fine-scale OR evolution and variation in African mole-rats (Bathyergidae, a family of subterranean rodents endemic to sub-Saharan Africa. Because of the selective pressures of life underground, enhanced olfaction is proposed to be fundamental to the evolutionary success of the Bathyergidae, resulting in a highly diversified OR gene-repertoire. Using a PCR-sequencing approach, we analysed variation in the OR7 family across 14 extant bathyergid species, which revealed enhanced levels of functional polymorphisms concentrated across the receptors' ligand-binding region. We propose that mole-rats are able to recognise a broad range of odorants and that this diversity is reflected throughout their OR7 gene repertoire. Using both classic tests and tree-based methods to test for signals of selection, we investigate evolutionary forces across the mole-rat OR7 gene tree. Four well-supported clades emerged in the OR phylogeny, with varying signals of selection; from neutrality to positive and purifying selection. Bathyergid life-history traits and environmental niche-specialisation are explored as possible drivers of adaptive OR evolution, emerging as non-exclusive contributors to the positive selection observed at OR7 genes. Our results reveal unexpected complexity of evolutionary mechanisms acting within a single OR family, providing insightful perspectives into OR evolutionary dynamics.

  5. Multidimensional MRI-CT atlas of the naked mole-rat brain

    Directory of Open Access Journals (Sweden)

    Fumiko eSeki

    2013-12-01

    Full Text Available Naked mole-rats have a variety of distinctive features such as the organisation of a hierarchical society (known as eusociality, extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI. Advanced MRI techniques such as diffusion tensor imaging (DTI, which generates high contrast images of fibre structures, can characterise unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography (CT were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualisation of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

  6. Naked mole-rat acid-sensing ion channel 3 forms nonfunctional homomers, but functional heteromers.

    Science.gov (United States)

    Schuhmacher, Laura-Nadine; Callejo, Gerard; Srivats, Shyam; Smith, Ewan St John

    2018-02-02

    Acid-sensing ion channels (ASICs) form both homotrimeric and heterotrimeric ion channels that are activated by extracellular protons and are involved in a wide range of physiological and pathophysiological processes, including pain and anxiety. ASIC proteins can form both homotrimeric and heterotrimeric ion channels. The ASIC3 subunit has been shown to be of particular importance in the peripheral nervous system with pharmacological and genetic manipulations demonstrating a role in pain. Naked mole-rats, despite having functional ASICs, are insensitive to acid as a noxious stimulus and show diminished avoidance of acidic fumes, ammonia, and carbon dioxide. Here we cloned naked mole-rat ASIC3 (nmrASIC3) and used a cell-surface biotinylation assay to demonstrate that it traffics to the plasma membrane, but using whole-cell patch clamp electrophysiology we observed that nmrASIC3 is insensitive to both protons and the non-proton ASIC3 agonist 2-guanidine-4-methylquinazoline. However, in line with previous reports of ASIC3 mRNA expression in dorsal root ganglia neurons, we found that the ASIC3 antagonist APETx2 reversibly inhibits ASIC-like currents in naked mole-rat dorsal root ganglia neurons. We further show that like the proton-insensitive ASIC2b and ASIC4, nmrASIC3 forms functional, proton-sensitive heteromers with other ASIC subunits. An amino acid alignment of ASIC3s between 9 relevant rodent species and human identified unique sequence differences that might underlie the proton insensitivity of nmrASIC3. However, introducing nmrASIC3 differences into rat ASIC3 (rASIC3) produced only minor differences in channel function, and replacing the nmrASIC3 sequence with that of rASIC3 did not produce a proton-sensitive ion channel. Our observation that nmrASIC3 forms nonfunctional homomers may reflect a further adaptation of the naked mole-rat to living in an environment with high-carbon dioxide levels. © 2018 by The American Society for Biochemistry and Molecular

  7. Androgen receptor distribution in the social decision-making network of eusocial naked mole-rats.

    Science.gov (United States)

    Holmes, Melissa M; Van Mil, Spencer; Bulkowski, Camila; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

    2013-11-01

    Naked mole-rats are highly social rodents that live in large groups and exhibit a strict reproductive and social hierarchy. Only a few animals in each colony breed; the remainder are non-reproductive and are socially subordinate to breeders. We have examined androgen receptor immunoreactive (AR+) cells in brain regions comprising the recently described social decision-making network in subordinate and breeder naked mole-rats of both sexes. We find that subordinates have a significantly higher percentage of AR+ cells in all brain regions expressing this protein. By contrast, there were no significant effects of sex and no sex-by-status interactions on the percentage of AR+ cells. Taken together with previous findings, the present data complete a systematic assessment of the distribution of AR protein in the social decision-making network of the eusocial mammalian brain and demonstrate a significant role for social status in the regulation of this protein throughout many nodes of this network. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Differential effects of chronic fluoxetine on the behavior of dominant and subordinate naked mole-rats.

    Science.gov (United States)

    Mongillo, Daniel L; Kosyachkova, Ekaterina A; Nguyen, Tam M; Holmes, Melissa M

    2014-01-01

    Naked mole-rats are eusocial rodents that live in large subterranean colonies with a strict reproductive and social hierarchy. The breeding female (referred to as the queen) and 1 to 3 breeding males are the only reproductive members of the colony. Breeders are socially dominant and all other colony members are non-reproductive subordinates. The effects of manipulating the serotonergic neurotransmitter system on aggression and dominance behaviors are well studied in many species, but not in eusocial rodents like the naked mole-rat. The current study investigated how the serotonergic system influences aggressive/dominant behaviors in this species. To do this, two separate but related experiments were conducted: the effects of fluoxetine hydrochloride (FLX) on status-specific behaviors of subordinates (Experiment 1) and dominant queens (Experiment 2) were evaluated both in-colony and in a social-pairing paradigm. In accordance with our main hypothesis, chronic treatment of FLX attenuated the frequency and duration of aggression in queens, but not subordinates, when paired with an unfamiliar conspecific. Further exploration of pharmacological manipulation on status-specific behaviors of this eusocial species may elucidate the neurobiological mechanisms underlying their unique and rigid social hierarchy. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

    Science.gov (United States)

    MacRae, Sheila L; Zhang, Quanwei; Lemetre, Christophe; Seim, Inge; Calder, Robert B; Hoeijmakers, Jan; Suh, Yousin; Gladyshev, Vadim N; Seluanov, Andrei; Gorbunova, Vera; Vijg, Jan; Zhang, Zhengdong D

    2015-04-01

    Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  11. Adaptation of pelage color and pigment variations in Israeli subterranean blind mole rats, Spalax ehrenbergi [corrected].

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    Natarajan Singaravelan

    Full Text Available Concealing coloration in rodents is well established. However, only a few studies examined how soil color, pelage color, hair-melanin content, and genetics (i.e., the causal chain synergize to configure it. This study investigates the causal chain of dorsal coloration in Israeli subterranean blind mole rats, Spalax ehrenbergi.We examined pelage coloration of 128 adult animals from 11 populations belonging to four species of Spalax ehrenbergi superspecies (Spalax galili, Spalax golani, Spalax carmeli, and Spalax judaei and the corresponding coloration of soil samples from the collection sites using a digital colorimeter. Additionally, we quantified hair-melanin contents of 67 animals using HPLC and sequenced the MC1R gene in 68 individuals from all four mole rat species.Due to high variability of soil colors, the correlation between soil and pelage color coordinates was weak and significant only between soil hue and pelage lightness. Multiple stepwise forward regression revealed that soil lightness was significantly associated with all pelage color variables. Pelage color lightness among the four species increased with the higher southward aridity in accordance to Gloger's rule (darker in humid habitats and lighter in arid habitats. Darker and lighter pelage colors are associated with darker basalt and terra rossa, and lighter rendzina soils, respectively. Despite soil lightness varying significantly, pelage lightness and eumelanin converged among populations living in similar soil types. Partial sequencing of the MC1R gene identified three allelic variants, two of which were predominant in northern species (S. galili and S. golani, and the third was exclusive to southern species (S. carmeli and S. judaei, which might have caused the differences found in pheomelanin/eumelanin ratio.Darker dorsal pelage in darker basalt and terra rossa soils in the north and lighter pelage in rendzina and loess soils in the south reflect the combined results of

  12. Vocalisations of the silvery mole-rat: comparasion of vocal repertoires in subterrane an rodents with different socials systems

    Czech Academy of Sciences Publication Activity Database

    Knotková, E.; Veitl, S.; Šumbera, R.; Sedláček, František; Burda, H.

    2009-01-01

    Roč. 18, č. 3 (2009), s. 241-257 ISSN 0952-4622 Institutional research plan: CEZ:AV0Z60870520 Keywords : silvery mole-rat * bathyergidae * vocal communication Subject RIV: EG - Zoology Impact factor: 1.050, year: 2009

  13. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

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    Antje Brand

    Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  14. A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition

    Science.gov (United States)

    Rodriguez, Karl A.; Osmulski, Pawel A.; Pierce, Anson; Weintraub, Susan T.; Gaczynska, Maria; Buffenstein, Rochelle

    2015-01-01

    The naked mole-rat maintains robust proteostasis and high levels of proteasome-mediated proteolysis for most of its exceptional (~31y) life span. Here, we report that the highly active proteasome from the naked mole-rat liver resists attenuation by a diverse suite of proteasome-specific small molecule inhibitors. Moreover, mouse, human, and yeast proteasomes exposed to the proteasome-depleted, naked mole-rat cytosolic fractions, recapitulate the observed inhibition resistance, and mammalian proteasomes also show increased activity. Gel filtration coupled with mass spectrometry and atomic force microscopy indicates that these traits are supported by a protein factor that resides in the cytosol. This factor interacts with the proteasome and modulates its activity. Although HSP72 and HSP40 (Hdj1) are among the constituents of this factor, the observed phenomenon, such as increasing peptidase activity and protecting against inhibition cannot be reconciled with any known chaperone functions. This novel function may contribute to the exceptional protein homeostasis in the naked mole-rat and allow it to successfully defy aging. PMID:25018089

  15. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Science.gov (United States)

    Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

    2010-12-21

    Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  16. Photic induction of Fos in the suprachiasmatic nucleus of African mole-rats: responses to increasing irradiance.

    Science.gov (United States)

    Oosthuizen, Maria K; Bennett, Nigel C; Cooper, Howard M

    2010-09-01

    African mole-rats (family Bathyergidae) are strictly subterranean rodent species that are rarely exposed to environmental light. Morphological and physiological adaptations to the underground environment include a severely reduced eye size and regressed visual system. Responses of the circadian system to light, however, appear to be intact, since mole-rats are able to entrain their circadian activity rhythms to the light-dark cycle and light induces Fos expression in the suprachiasmatic nucleus (SCN). Social organization varies from solitary species to highly elaborated eusocial structures, characterized by a distinct division of labor and in which one reproductive female regulates the behavior and reproductive physiology of other individuals in the colony. The authors studied light-induced Fos expression in the SCN to increasing light intensities in four mole-rat species, ranging from strictly solitary to highly social. In the solitary Cape mole-rat, light induces significant Fos expression in the SCN, and the number of Fos-immunopositive cells increases with increasing light intensity. In contrast, Fos induction in the SCN of social species was slightly greater than, but not statistically different from, the dark-control animals as is typical of most rodents. One species showed a trend for an increase in expression with increased light, whereas a second species showed no trend in expression. In the naked mole-rat, Fos expression appeared higher in the dark-controls than in the animals exposed to light, although the differences in Fos expression were not significant. These results suggest a gradient in the sensitivity of the circadian system to light in mole-rats, with a higher percentage of individuals that are unresponsive to light in correlation with the degree of sociality. In highly social species, such as the naked mole-rat that live in a relatively stable subterranean milieu in terms of food availability, temperature, constant darkness, and devoid of 24-h

  17. Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

    Science.gov (United States)

    Schuhmacher, Laura-Nadine; Smith, Ewan St John

    2016-12-13

    Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

  18. Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

    Science.gov (United States)

    Peterson, Bethany L; Park, Thomas J; Larson, John

    2012-01-11

    Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Li Tan

    2017-11-01

    Full Text Available Naked mole rat (NMR is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming. Analysis of the global histone landscape revealed that NMR had higher levels of repressive H3K27 methylation marks and lower levels of activating H3K27 acetylation marks than mouse. ATAC-seq revealed that in NMR, promoters of reprogramming genes were more closed than mouse promoters, while expression of LT led to massive opening of the NMR promoters. These results suggest that NMR displays a more stable epigenome that resists de-differentiation, contributing to the cancer resistance and longevity of this species.

  20. Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera

    Directory of Open Access Journals (Sweden)

    Sang-Goo Lee

    2017-11-01

    Full Text Available Naked mole rats (NMRs are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.

  1. Functional characteristics of the naked mole rat μ-opioid receptor.

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    Melanie Busch-Dienstfertig

    Full Text Available While humans and most animals respond to µ-opioid receptor (MOR agonists with analgesia and decreased aggression, in the naked mole rat (NMR opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1 can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.

  2. Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

    Science.gov (United States)

    Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

    2014-03-01

    The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

  3. Cessation of reproduction-related spine elongation after multiple breeding cycles in female naked mole-rats.

    Science.gov (United States)

    Dengler-Crish, Christine M; Catania, Kenneth C

    2009-01-01

    The breeding female or "queen" naked mole-rat has a uniquely elongated body morphology attributed to the lengthening of the lumbar vertebral column that occurs during pregnancy. It is unknown whether this vertebral growth is a continuous process, or associated only with early reproductive experience. We compared pregnancy-related bone elongation in nascent primiparous queens and established queens to determine if this vertebral expansion was a lifelong process in these females. We also investigated the impact of lactation on vertebral elongation in these mole-rats because it is known to be a time of significant bone loss in other mammals. Our data show that after eight or more pregnancies, established queens no longer experienced a net gain in lumbar spine length over the reproductive cycle, whereas the nascent breeders demonstrated significant spine lengthening over this time. Despite the lack of net spine lengthening in established breeders, our results indicated that these queens still experienced some pregnancy-specific vertebral elongation. In naked mole-rats, pregnancy-induced bone elongation may serve the dual purposes of first lengthening the spine, and then once optimal spine size is achieved, serving as a homeostatic mechanism that prepares the spine for the mineral demands of lactation. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

  4. Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

    Science.gov (United States)

    Henning, Yoshiyuki; Mladěnková, Nella; Burda, Hynek; Szafranski, Karol; Begall, Sabine

    2018-03-12

    Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

  5. Non-invasive assessment of glucocorticoid and androgen metabolite levels in cooperatively breeding Damaraland mole-rats (Fukomys damarensis).

    Science.gov (United States)

    Medger, Katarina; Bennett, Nigel C; Lutermann, Heike; Ganswindt, Andre

    2018-05-18

    Dominant females of cooperative breeding species often use aggression to suppress reproduction of subordinate females, resulting in subordinates experiencing stress-related increases in glucocorticoid levels, which may cause reproductive down-regulation. This would suggest a general pattern with higher glucocorticoid levels in subordinate compared to dominant individuals; however, the opposite was found in a number of cooperatively breeding species. Furthermore, breeding females of the cooperatively breeding Damaraland mole-rats (Fukomys damarensis) exhibit very high androgen concentrations during the wet season, presumably to support their breeding monopoly. Hormone analysis in Damaraland mole-rats have typically been measured using plasma and urine, but faecal analysis offers additional advantages especially for field studies on this species. The present study examines the suitability of Damaraland mole-rat faecal samples for determining glucocorticoid metabolite (fGCM) and androgen metabolite (fAM) concentrations using enzyme immunoassays. Using these assays, we further evaluated the effects of breeding status on fGCM and fAM concentrations in wild-caught and captive Damaraland mole-rats. Wild-caught breeding and non-breeding males and females exhibited no differences in fAM concentrations. Immunoreactive fGCM concentrations were only high in male breeders and comparatively low in non-breeders and breeding females. Concentrations of fAMs and fGCMs were similar in captive males and females, but fAM concentrations were elevated in captive compared to wild-caught individuals, which may be related to a higher reproductive activity due to removal from the breeding female. The relatively uniform fAM and fGCM concentrations found in wild-caught mole-rats may be explained by a stable colony structure during the dry season during which this study was conducted. Limited dispersal opportunities result in lower aggression and stress levels within a colony and as a result

  6. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

    Science.gov (United States)

    Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

    2014-01-01

    Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

  7. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Henning

    Full Text Available Ansell's mole-rats (Fukomys anselli are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a their thyroid hormone system shows any peculiarities on the genetic level, b these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs, and c reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

  8. Gis-approach for variability assessment of soil electric conductivity under pedoturbation activity of mole rat (Spalax microphthalmus

    Directory of Open Access Journals (Sweden)

    T. М. Konovalova

    2010-06-01

    Full Text Available The results of the investigation of the impact of the mole rat’s activity on soil electric conductivity have been presented. GIS-technology have been shown to be effective for assessment of the pedoturbation activity effect on the soil surface heterogeneity formation. Method of the one-dimension spatial coordinated array transformation into matrix form has been proposed for following multidimension statistic analysis application. The quantity estimation of the mole rats role in formation of the habitat nanorelief-level diversity has been obtained by means of indexes of the landscape complexity and diversity.

  9. Fos expression in the suprachiasmatic nucleus in response to light stimulation in a solitary and social species of African mole-rat (family Bathyergidae).

    Science.gov (United States)

    Oosthuizen, M K; Bennett, N C; Cooper, H M

    2005-01-01

    Mole-rats are strictly subterranean rodents that are rarely exposed to environmental light. They are well adapted to their environment and have reduced eyes and a severely regressed visual system. It has been shown, however, that mole-rats do exhibit endogenous circadian rhythms that can be entrained, suggesting an intact and functional circadian system. To determine whether light is the entraining agent in these animals, Fos expression in response to light pulses at different circadian times was investigated to obtain phase response curves. Light is integrated effectively in the suprachiasmatic nucleus of the Cape mole-rat (Georychus capensis), and Fos expression is gated according to the phase of the circadian clock. The Fos response in the Cape mole-rat was comparable to that of aboveground rodents. In contrast, the highveld mole-rat (Cryptomys hottentotus pretoriae) was less sensitive to light and did not show a selective Fos response according to the phase of the circadian cycle. Social species appear to be less sensitive to light than their solitary counterparts, which compares well with results from locomotor activity studies.

  10. Transcriptome sequencing of the blind subterranean mole rat, Spalax galili: Utility and potential for the discovery of novel evolutionary patterns

    KAUST Repository

    Malik, Assaf

    2011-08-12

    The blind subterranean mole rat (Spalax ehrenbergi superspecies) is a model animal for survival under extreme environments due to its ability to live in underground habitats under severe hypoxic stress and darkness. Here we report the transcriptome sequencing of Spalax galili, a chromosomal type of S. ehrenbergi. cDNA pools from muscle and brain tissues isolated from animals exposed to hypoxic and normoxic conditions were sequenced using Sanger, GS FLX, and GS FLX Titanium technologies. Assembly of the sequences yielded over 51,000 isotigs with homology to ~12,000 mouse, rat or human genes. Based on these results, it was possible to detect large numbers of splice variants, SNPs, and novel transcribed regions. In addition, multiple differential expression patterns were detected between tissues and treatments. The results presented here will serve as a valuable resource for future studies aimed at identifying genes and gene regions evolved during the adaptive radiation associated with underground life of the blind mole rat. 2011 Malik et al.

  11. Exceptional Chromosomal Evolution and Cryptic Speciation of Blind Mole Rats Nannospalax leucodon (Spalacinae, Rodentia from South-Eastern Europe

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    Ivo Savić

    2017-10-01

    Full Text Available Mole rats are exclusively subterranean and highly specialized rodents. Their long lifespans, remarkable anti-cancer mechanisms, and various distinctive adaptive features make them a useful research model. Moreover, opposing convergence of morphological traits, they have developed extremely high karyotype variability. Thus, 74 chromosomal forms have been described so far and new ones are being revealed continuously. These evolved during the process of rapid radiation and occur in different biogeographical regions. During research into their reproductive biology we have already provided substantial evidence for species-level separation of these taxa. Here, we review diverse chromosomal forms of the lesser blind mole rat, Mediterranean Nannospalax leucodon, distributed in South-eastern Europe, their karyotype records, biogeography, origin, and phylogeny from our extensive research. In the light of new data from molecular genetic studies, we question some former valuations and propose a cryptospecies rank for seven reproductively isolated chromosomal forms with sympatric and parapatric distribution and clear ecogeographical discrepances in their habitats, as well as new experimental and theoretical methods for understanding the courses of speciation of these unique fossorial mammals.

  12. The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Susanne Kurz

    Full Text Available Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

  13. The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

    Science.gov (United States)

    Kurz, Susanne; Thieme, René; Amberg, Ronny; Groth, Marco; Jahnke, Heinz-Georg; Pieroh, Philipp; Horn, Lars-Christian; Kolb, Marlen; Huse, Klaus; Platzer, Matthias; Volke, Daniela; Dehghani, Faramarz; Buzdin, Anton; Engel, Kathrin; Robitzki, Andrea; Hoffmann, Ralf; Gockel, Ines; Birkenmeier, Gerd

    2017-01-01

    Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

  14. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species.

    Science.gov (United States)

    Buffenstein, Rochelle

    2008-05-01

    Aging refers to a gradual deterioration in function that, over time, leads to increased mortality risk, and declining fertility. This pervasive process occurs in almost all organisms, although some long-lived trees and cold water inhabitants reportedly show insignificant aging. Negligible senescence is characterized by attenuated age-related change in reproductive and physiological functions, as well as no observable age-related gradual increase in mortality rate. It was questioned whether the longest living rodent, the naked mole-rat, met these three strict criteria. Naked mole-rats live in captivity for more than 28.3 years, approximately 9 times longer than similar-sized mice. They maintain body composition from 2 to 24 years, and show only slight age-related changes in all physiological and morphological characteristics studied to date. Surprisingly breeding females show no decline in fertility even when well into their third decade of life. Moreover, these animals have never been observed to develop any spontaneous neoplasm. As such they do not show the typical age-associated acceleration in mortality risk that characterizes every other known mammalian species and may therefore be the first reported mammal showing negligible senescence over the majority of their long lifespan. Clearly physiological and biochemical processes in this species have evolved to dramatically extend healthy lifespan. The challenge that lies ahead is to understand what these mechanisms are.

  15. Walking the oxidative stress tightrope: a perspective from the naked mole-rat, the longest-living rodent.

    Science.gov (United States)

    Rodriguez, Karl A; Wywial, Ewa; Perez, Viviana I; Lambert, Adriant J; Edrey, Yael H; Lewis, Kaitlyn N; Grimes, Kelly; Lindsey, Merry L; Brand, Martin D; Buffenstein, Rochelle

    2011-01-01

    Reactive oxygen species (ROS), by-products of aerobic metabolism, cause oxidative damage to cells and tissue and not surprisingly many theories have arisen to link ROS-induced oxidative stress to aging and health. While studies clearly link ROS to a plethora of divergent diseases, their role in aging is still debatable. Genetic knock-down manipulations of antioxidants alter the levels of accrued oxidative damage, however, the resultant effect of increased oxidative stress on lifespan are equivocal. Similarly the impact of elevating antioxidant levels through transgenic manipulations yield inconsistent effects on longevity. Furthermore, comparative data from a wide range of endotherms with disparate longevity remain inconclusive. Many long-living species such as birds, bats and mole-rats exhibit high-levels of oxidative damage, evident already at young ages. Clearly, neither the amount of ROS per se nor the sensitivity in neutralizing ROS are as important as whether or not the accrued oxidative stress leads to oxidative-damage-linked age-associated diseases. In this review we examine the literature on ROS, its relation to disease and the lessons gleaned from a comparative approach based upon species with widely divergent responses. We specifically focus on the longest lived rodent, the naked mole-rat, which maintains good health and provides novel insights into the paradox of maintaining both an extended healthspan and lifespan despite high oxidative stress from a young age.

  16. The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

    Science.gov (United States)

    Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

    2017-12-01

    The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

  17. Spatial and temporal activity patterns of the free-living giant mole-rat (Fukomys mechowii, the largest social bathyergid.

    Directory of Open Access Journals (Sweden)

    Matěj Lövy

    Full Text Available Despite the considerable attention devoted to the biology of social species of African mole-rats (Bathyergidae, Rodentia, knowledge is lacking about their behaviour under natural conditions. We studied activity of the largest social bathyergid, the giant mole-rat Fukomys mechowii, in its natural habitat in Zambia using radio-telemetry. We radio-tracked six individuals during three continuous 72-h sessions. Five of these individuals, including a breeding male, belonged to a single family group; the remaining female was probably a solitary disperser. The non-breeders of the family were active (i.e. outside the nest 5.8 hours per 24h-day with the activity split into 6.5 short bouts. The activity was more concentrated in the night hours, when the animals also travelled longer distances from the nest. The breeding male spent only 3.2 hours per day outside the nest, utilizing less than 20% of the whole family home range. The dispersing female displayed a much different activity pattern than the family members. Her 8.0 hours of outside-nest activity per day were split into 4.6 bouts which were twice as long as in the family non-breeders. Her activity peak in the late afternoon coincided with the temperature maximum in the depth of 10 cm (roughly the depth of the foraging tunnels. Our results suggest that the breeding individuals (at least males contribute very little to the work of the family group. Nevertheless, the amount of an individual's activity and its daily pattern are probably flexible in this species and can be modified in response to actual environmental and social conditions.

  18. Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat.

    Science.gov (United States)

    Triplett, Judy C; Swomley, Aaron; Kirk, Jessime; Lewis, Katilyn; Orr, Miranda; Rodriguez, Karl; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

    2015-08-01

    Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground in a thermally stable ecological niche, NMRs have evolved certain exceptional traits, resulting in sustained health spans, negligible cognitive decline, and a pronounced resistance to age-related disease. Uncovering insights into mechanisms underlying these extraordinary traits involved in successful aging may conceivably provide crucial clues to extend the human life span and health span. One of the most fundamental processes inside the cell is the production of ATP, which is an essential fuel in driving all other energy-requiring cellular activities. Not surprisingly, a prominent hallmark in age-related diseases, such as neurodegeneration and cancer, is the impairment and dysregulation of metabolic pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics approach, alterations in expression and phosphorylation levels of metabolic proteins in the brains of NMRs, aged 2-24 years, were evaluated in an age-dependent manner. We identified 13 proteins with altered levels and/or phosphorylation states that play key roles in various metabolic pathways including glycolysis, β-oxidation, the malate-aspartate shuttle, the Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH production, as well as the production of glutamate. New insights into potential pathways involved in metabolic aspects of successful aging have been obtained by the identification of key proteins through which the NMR brain responds and adapts to the aging process and how the NMR brain adapted to resist age-related degeneration. This study examines the changes in the proteome and phosphoproteome in the brain of the naked mole-rat aged 2-24 years. We identified 13 proteins (labeled in red) with altered expression and/or phosphorylation levels that are conceivably associated with sustained metabolic functions in the oldest NMRs that may promote a sustained health span and life span.

  19. Parentage analysis of Ansell’s mole-rat family groups indicates a high reproductive skew despite relatively relaxed ecological constraints on dispersal

    Czech Academy of Sciences Publication Activity Database

    Patzenhauerová, Hana; Šklíba, J.; Bryja, Josef; Šumbera, R.

    2013-01-01

    Roč. 22, č. 19 (2013), s. 4988-5000 ISSN 0962-1083 R&D Projects: GA AV ČR IAA601410802; GA ČR GAP506/10/0983 Institutional support: RVO:68081766 Keywords : African mole-rat * dispersal * eusociality * Fukomys * mating system * reproductive skew Subject RIV: EH - Ecology, Behaviour Impact factor: 5.840, year: 2013

  20. Variability of space-use patterns in a free living eusocial rodent, Ansell’s mole-rat indicates age-based rather than caste polyethism

    Czech Academy of Sciences Publication Activity Database

    Šklíba, Jan; Lövy, M.; Burda, H.; Šumbera, R.

    2016-01-01

    Roč. 6, DEC 06 (2016), č. článku 37497. ISSN 2045-2322 EU Projects: European Commission(XE) 669609 - Diversity6continents Institutional support: RVO:60077344 Keywords : eusocial rodent * mole-rats * Fukomys anselli Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 4.259, year: 2016 https://www.nature.com/articles/srep37497

  1. Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice.

    Science.gov (United States)

    Andziak, Blazej; Buffenstein, Rochelle

    2006-12-01

    A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P naked mole-rats is independent of oxidative stress parameters.

  2. Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis).

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    Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

    2013-01-01

    A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar environments and reference memory in the solitary Cape mole-rat (Georychus capensis). Our data showed that both wild and captive animals readily explore open spaces and tunnels. Wild animals were however more active than their captive counterparts. In the Y maze two trial discrimination task, wild animals failed to discriminate between novel and familiar environments, while laboratory housed mole-rats showed preferential spatial discrimination in terms of the length of time spent in the novel arm. The performance of the laboratory and wild animals were similar when tested for reference memory in the Y maze, both groups showed a significant improvement compared to the first day, from the 3rd day onwards. Wild animals made more mistakes whereas laboratory animals were slower in completing the task. The difference in performance between wild and laboratory animals in the Y-maze may be as a result of the lower activity of the laboratory animals. Laboratory maintained Cape mole-rats show classic behaviours resulting from a lack of stimulation such as reduced activity and increased aggression. However, they do display an improved novelty discrimination compared to the wild animals. Slower locomotion rate of the laboratory animals may increase the integration time of stimuli, hence result in a more thorough inspection of the surroundings. Unlike the captive animals, wild animals show flexibility in their responses to unpredictable events, which is an important requirement under

  3. Low sulfide levels and a high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat.

    Science.gov (United States)

    Dziegelewska, Maja; Holtze, Susanne; Vole, Christiane; Wachter, Ulrich; Menzel, Uwe; Morhart, Michaela; Groth, Marco; Szafranski, Karol; Sahm, Arne; Sponholz, Christoph; Dammann, Philip; Huse, Klaus; Hildebrandt, Thomas; Platzer, Matthias

    2016-08-01

    Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Low sulfide levels and a high degree of cystathionine β-synthase (CBS activation by S-adenosylmethionine (SAM in the long-lived naked mole-rat

    Directory of Open Access Journals (Sweden)

    Maja Dziegelewska

    2016-08-01

    Full Text Available Hydrogen sulfide (H2S is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS, an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration.

  5. They live in the land down under: thyroid function and basal metabolic rate in the Blind Mole Rat, Spalax.

    Science.gov (United States)

    Avivi, Aaron; Nevo, Eviatar; Cohen, Keren; Sotnichenko, Nick; Hercbergs, Aleck; Band, Mark; Davis, Paul J; Ellis, Martin; Ashur-Fabian, Osnat

    2014-01-01

    The Israeli blind subterranean mole rat (Spalax ehrenbergi superspecies) lives in sealed underground burrows under extreme, hypoxic conditions. The four Israeli Spalax allospecies have adapted to different climates, the cool-humid (Spalax galili, 2 n = 52 chromosomes), semihumid (S. golani, 2 n = 54) north regions, warm-humid (S. carmeli, 2 n = 58) central region and the warm-dry S. judaei, 2 n = 60) southern regions. A dramatic interspecies decline in basal metabolic rate (BMR) from north to south, even after years of captivity, indicates a genetic basis for this BMR trait. We examined the possibility that the genetically-conditioned interspecies BMR difference was expressed via circulating thyroid hormone. An unexpected north to south increase in serum free thyroxine (FT4) and total 3, 5, 3'-triiodo-L-thyronine (T3) (p BMR measurements. The increases in serum FT4 and T3 were symmetrical, so that the T3:FT4 ratio - interpretable as an index of conversion of T4 to T3 in nonthyroidal tissues - did not support relative decrease in production of T3 as a contributor to BMR. Increased north-to-south serum FT4 and T3 levels also correlated negatively with hemoglobin/hematocrit. North-to-south adaptations in spalacids include decreased BMR and hematocrit/hemoglobin in the face of increasing thyroid hormone levels, arguing for independent control of hormone secretion and BMR/hematocrit/hemoglobin. But the significant inverse relationship between thyroid hormone levels and BMR/hematocrit/hemoglobin is also consistent with a degree of cellular resistance to thyroid hormone action that protects against hormone-induced increase in oxygen consumption in a hostile, hypoxic environment.

  6. Reproduction is associated with a tissue-dependent reduction of oxidative stress in eusocial female Damaraland mole-rats (Fukomys damarensis.

    Directory of Open Access Journals (Sweden)

    Christina M Schmidt

    Full Text Available Oxidative stress has been implicated as both a physiological cost of reproduction and a driving force on an animal's lifespan. Since increased reproductive effort is generally linked with a reduction in survival, it has been proposed that oxidative stress may influence this relationship. Support for this hypothesis is inconsistent, but this may, in part, be due to the type of tissues that have been analyzed. In Damaraland mole-rats the sole reproducing female in the colony is also the longest lived. Therefore, if oxidative stress does impact the trade-off between reproduction and survival in general, this species may possess some form of enhanced defense. We assessed this relationship by comparing markers of oxidative damage (malondialdehyde, MDA; protein carbonyls, PC and antioxidants (total antioxidant capacity, TAC; superoxide dismutase, SOD in various tissues including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between wild-caught reproductive and non-reproductive female Damaraland mole-rats. Reproductive females exhibited significantly lower levels of PC across all tissues, and lower levels of MDA in heart, kidney and liver relative to non-reproductive females. Levels of TAC and SOD did not differ significantly according to reproductive state. The reduction in oxidative damage in breeding females may be attributable to the unusual social structure of this species, as similar relationships have been observed between reproductive and non-reproductive eusocial insects.

  7. How attractive is the girl next door? An assessment of spatial mate acquisition and paternity in the solitary Cape dune mole-rat, Bathyergus suillus.

    Directory of Open Access Journals (Sweden)

    Timothy C Bray

    Full Text Available Behavioural observations of reproduction and mate choice in wild fossorial rodents are extremely limited and consequently indirect methods are typically used to infer mating strategies. We use a combination of morphological, reproductive, spatial, and genetic data to investigate the reproductive strategy of a solitary endemic species, the Cape dune mole-rat Bathyergus suillus. These data provide the first account on the population dynamics of this species. Marked sexual dimorphism was apparent with males being both significantly larger and heavier than females. Of all females sampled 36% had previously reproduced and 12% were pregnant at the time of capture. Post-partum sex ratio was found to be significantly skewed in favour of females. The paternity of fifteen litters (n = 37 was calculated, with sires assigned to progeny using both categorical and full probability methods, and including a distance function. The maximum distance between progeny and a putative sire was determined as 2149 m with males moving between sub-populations. We suggest that above-ground movement should not be ignored in the consideration of mate acquisition behaviour of subterranean mammals. Estimated levels of multiple paternity were shown to be potentially as high as 26%, as determined using sibship and sire assignment methods. Such high levels of multiple paternity have not been found in other solitary mole-rat species. The data therefore suggest polyandry with no evidence as yet for polygyny.

  8. Reaching Out to Send a Message: Proteins Associated with Neurite Outgrowth and Neurotransmission are Altered with Age in the Long-Lived Naked Mole-Rat.

    Science.gov (United States)

    Triplett, Judy C; Swomley, Aaron M; Kirk, Jessime; Grimes, Kelly M; Lewis, Kaitilyn N; Orr, Miranda E; Rodriguez, Karl A; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

    2016-07-01

    Aging is the greatest risk factor for developing neurodegenerative diseases, which are associated with diminished neurotransmission as well as neuronal structure and function. However, several traits seemingly evolved to avert or delay age-related deterioration in the brain of the longest-lived rodent, the naked mole-rat (NMR). The NMR remarkably also exhibits negligible senescence, maintaining an extended healthspan for ~75 % of its life span. Using a proteomic approach, statistically significant changes with age in expression and/or phosphorylation levels of proteins associated with neurite outgrowth and neurotransmission were identified in the brain of the NMR and include: cofilin-1; collapsin response mediator protein 2; actin depolymerizing factor; spectrin alpha chain; septin-7; syntaxin-binding protein 1; synapsin-2 isoform IIB; and dynamin 1. We hypothesize that such changes may contribute to the extended lifespan and healthspan of the NMR.

  9. Extended postnatal brain development in the longest-lived rodent: prolonged maintenance of neotenous traits in the naked mole-rat brain

    Directory of Open Access Journals (Sweden)

    Miranda E. Orr

    2016-11-01

    Full Text Available The naked mole-rat (NMR is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to three years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At four months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until nine months of age in NMRs, and synaptic protein expression continues to change throughout the first three years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through six weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short

  10. Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain.

    Science.gov (United States)

    Orr, Miranda E; Garbarino, Valentina R; Salinas, Angelica; Buffenstein, Rochelle

    2016-01-01

    The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.

  11. Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease.

    Science.gov (United States)

    Edrey, Yael H; Medina, David X; Gaczynska, Maria; Osmulski, Pawel A; Oddo, Salvatore; Caccamo, Antonella; Buffenstein, Rochelle

    2013-10-01

    Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2-20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Origin and diversification of Hibiscus glaber, species endemic to the oceanic Bonin Islands, revealed by chloroplast DNA polymorphism.

    Science.gov (United States)

    Takayama, Koji; Ohi-Toma, Tetsuo; Kudoh, Hiroshi; Kato, Hidetoshi

    2005-04-01

    Abstract Two woody Hibiscus species co-occur in the Bonin Islands of the northwestern Pacific Ocean: Hibiscus glaber Matsum. is endemic to the islands, and its putative ancestral species, Hibiscus tiliaceus L., is widely distributed in coastal areas of the tropics and subtropics. To infer isolating mechanisms that led to speciation of H. glaber and the processes that resulted in co-occurrence of the two closely related species on the Bonin Islands, we conducted molecular phylogenetic analyses on chloroplast DNA (cpDNA) sequences. Materials collected from a wide area of the Pacific and Indian Oceans were used, and two closely related species, Hibiscus hamabo Siebold Zucc. and Hibiscus macrophyllus Roxb., were also included in the analyses. The constructed tree suggested that H. glaber has been derived from H. tiliaceus, and that most of the modern Bonin populations of H. tiliaceus did not share most recent ancestry with H. glaber. Geographic isolation appears to be the most important mechanism in the speciation of H. glaber. The co-occurrence of the two species can be attributed to multiple migrations of different lineages into the islands. While a wide and overlapping geographical distribution of haplotypes was found in H. tiliaceus, localized geographical distribution of haplotypes was detected in H. glaber. It is hypothesized that a shift to inland habitats may have affected the mode of seed dispersal from ocean currents to gravity and hence resulted in geographical structuring of H. glaber haplotypes.

  13. And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat.

    Science.gov (United States)

    Grimes, Kelly M; Reddy, Anilkumar K; Lindsey, Merry L; Buffenstein, Rochelle

    2014-08-01

    The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans.

  14. Characterization of gonadotrophin-releasing hormone precursor cDNA in the Old World mole-rat Cryptomys hottentotus pretoriae: high degree of identity with the New World guinea pig sequence.

    Science.gov (United States)

    Kalamatianos, T; du Toit, L; Hrabovszky, E; Kalló, I; Marsh, P J; Bennett, N C; Coen, C W

    2005-05-01

    Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as 'mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the 'mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the 'mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic 'mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63-45 million years ago.

  15. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

    Science.gov (United States)

    Thieme, René; Kurz, Susanne; Kolb, Marlen; Debebe, Tewodros; Holtze, Susanne; Morhart, Michaela; Huse, Klaus; Szafranski, Karol; Platzer, Matthias; Hildebrandt, Thomas B; Birkenmeier, Gerd

    2015-01-01

    The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M. Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL) and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL) in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma. We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti

  16. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

    Directory of Open Access Journals (Sweden)

    René Thieme

    Full Text Available The naked mole-rat (NMR is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M.Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma.We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the

  17. Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

    DEFF Research Database (Denmark)

    Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

    2016-01-01

    The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer...... marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly...... synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells...

  18. Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

    Science.gov (United States)

    Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

    2014-02-07

    Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

  19. Metal accumulation in the smooth toadfish, Tetractenos glaber, in estuaries around Sydney, Australia

    International Nuclear Information System (INIS)

    Alquezar, Ralph; Markich, Scott J.; Booth, David J.

    2006-01-01

    This study determined the metal levels in sediments and tissues of a common estuarine fish, Tetractenos glaber (smooth toadfish), from two metal contaminated and two reference estuaries near Sydney, Australia. Metal levels were highest in sediments and fish from contaminated estuaries. Gonads contained the highest metal levels followed by muscle, gill and liver. Metal accumulation was gender-dependant (e.g. male gonads were >20 times higher in As than females; female gills were >30 times higher than males for Pb). Cadmium, Pb and Ni levels in fish tissues reflected sediment levels, indicating sediment and/or dietary metal uptake. Levels of As, Co, Cd and Pb in gills showed similar patterns to other tissues, suggesting that metals may have been taken up by gills through contaminated water. Similar metal patterns in tissues and sediments suggest more than one uptake pathway. This study indicates that multiple factors influence metal accumulation in fish. - Metal levels in toadfish tissues reflect sediment metal levels and show gender differences

  20. Oxidative and interactive challenge of cadmium and ocean acidification on the smooth scallop Flexopecten glaber.

    Science.gov (United States)

    Nardi, Alessandro; Benedetti, Maura; Fattorini, Daniele; Regoli, Francesco

    2018-03-01

    Ocean acidification (OA) may affect sensitivity of marine organisms to metal pollution modulating chemical bioavailability, bioaccumulation and biological responsiveness of several cellular pathways. In this study, the smooth scallop Flexopecten glaber was exposed to various combinations of reduced pH (pH/pCO 2 7.4/∼3000 μatm) and Cd (20 μg/L). The analyses on cadmium uptake were integrated with those of a wide battery of biomarkers including metallothioneins, single antioxidant defenses and total oxyradical scavenging capacity in digestive gland and gills, lysosomal membrane stability and onset of genotoxic damage in haemocytes. Reduced pH slightly increased concentration of Cd in scallop tissues, but no effects were measured in terms of metallothioneins. Induction of some antioxidants by Cd and/or low pH in the digestive gland was not reflected in variations of the total oxyradical scavenging capacity, while the investigated stressors caused a certain inhibition of antioxidants and reduction of the scavenging capacity toward peroxyl radical in the gills. Lysosomal membrane stability and onset of genotoxic damages showed high sensitivity with possible synergistic effects of the investigated factors. The overall results suggest that indirect effects of ocean acidification on metal accumulation and toxicity are tissue-specific and modulate oxidative balance through different mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. HPLC, NMR and MALDI-TOF MS analysis of condensed tannins from Lithocarpus glaber leaves with potent free radical scavenging activity.

    Science.gov (United States)

    Zhang, Liang Liang; Lin, Yi Ming

    2008-12-04

    Using acid-catalyzed degradation in the presence of cysteamine, the condensed tannins from Lithocarpus glaber leaves were characterized, following thiolysis, by means of reversed-phase HPLC, 13C-NMR and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analyses. The thiolysis reaction products showed the presence of the procyanidin (PC) and prodelphinidin (PD) structures. The 13C-NMR spectrum revealed that the condensed tannins were comprised of PD (72.4%) and PC (27.6%), and with a greater content of cis configuration rather than the trans configuration of C2-C3. The MALDI-TOF MS analysis proved the presence of PD units, and the maximum degree of polymerization (DP) was an undecamer. The antioxidant activity of condensed tannins from L. glaber leaves was evaluated by using a free radical scavenging activity assay.

  2. HPLC, NMR and MALDI-TOF MS Analysis of Condensed Tannins from Lithocarpus glaber Leaves with Potent Free Radical Scavenging Activity

    OpenAIRE

    Zhang, Liang Liang; Lin, Yi Ming

    2008-01-01

    Using acid-catalyzed degradation in the presence of cysteamine, the condensed tannins from Lithocarpus glaber leaves were characterized, following thiolysis, by means of reversed-phase HPLC, 13C-NMR and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analyses. The thiolysis reaction products showed the presence of the procyanidin (PC) and prodelphinidin (PD) structures. The 13C-NMR spectrum revealed that the condensed tannins were comprised of PD (7...

  3. Oxidative Stress in Aging: Advances in Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Daniel Ortuño-Sahagún

    2014-01-01

    Full Text Available Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL. Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS], which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8, naked mole-rat (Heterocephalus glaber, and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS and oxidative stress in aging.

  4. Comparative accumulation of 109Cd and 75Se from water and food by an estuarine fish (Tetractenos glaber)

    International Nuclear Information System (INIS)

    Alquezar, Ralph; Markich, Scott J.; Twining, John R.

    2008-01-01

    Few data are available on the comparative accumulation of metal(loid)s from water and food in estuarine/marine fish. Smooth toadfish (Tetractenos glaber), commonly found in estuaries in south-eastern Australia, were separately exposed to radio-labelled seawater (14 kBq L -1 of 109 Cd and 24 kBq L -1 of 75 Se) and food (ghost shrimps; Trypaea australiensis: 875 Bq g -1109 Cd and 1130 Bq g -175 Se) for 25 days (uptake phase), followed by exposure to radionuclide-free water or food for 30 days (loss phase). Toadfish accumulated 109 Cd predominantly from water (85%) and 75 Se predominantly from food (62%), although the latter was lower than expected. For both the water and food exposures, 109 Cd was predominantly located in the gut lining (60-75%) at the end of the uptake phase, suggesting that the gut may be the primary pathway of 109 Cd uptake. This may be attributed to toadfish drinking large volumes of water to maintain osmoregulation. By the end of the loss phase, 109 Cd had predominantly shifted to the excretory organs - the liver (81%) in toadfish exposed to radio-labelled food, and in the liver, gills and kidney (82%) of toadfish exposed to radio-labelled water. In contrast, 75 Se was predominantly located in the excretory organs (gills, kidneys and liver; 66-76%) at the end of the uptake phase, irrespective of the exposure pathway, with minimal change in percentage distribution (76-83%) after the loss phase. This study emphasises the importance of differentiating accumulation pathways to better understand metal(loid) transfer dynamics and subsequent toxicity, in aquatic biota

  5. Development and characterization of microsatellite markers for Hibiscus glaber Matsum. ex Nakai, an endemic tree species of the oceanic Bonin Islands, Japan.

    Science.gov (United States)

    Ohtani, Masato; Tani, Naoki; Yoshimaru, Hiroshi

    2008-11-01

    Polymorphic microsatellite markers were developed for Hibiscus glaber, an endemic tree of the Bonin Islands. Eighty-seven of the 208 sequences from an enriched library were unique and containing microsatellites. Ten loci were proved to be highly polymorphic among 78 individuals from the Nishi-jima Island. Total exclusionary powers for the first and the second parents were 99.989% and 99.999%, respectively. Nine loci also amplified single fragment from genomic DNA of H. tiliaceus, a related and widespread congener. Our markers can be reliably used for the estimation of current gene flow within/among populations of the two woody Hibiscus species. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.

  6. ACTIVITY PATTERNS IN THE MOLE-RATS TACHYORYCTES ...

    African Journals Online (AJOL)

    Heilophoblus spends over 50 % of the day out of its nest, Tachyoryctes, ..... Surface foraging through an open hole and mole-hill formation could be directly ..... Heliophobius fed at irregular intervals throughout the day and night (Jarvis, ...

  7. Burrow architecture, family composition and habitat characteristics of the largest social African mole-rat: the giant mole-rat constructs really giant burrow systems

    Czech Academy of Sciences Publication Activity Database

    Šumbera, R.; Mazoch, V.; Patzenhauerová, Hana; Lövy, M.; Šklíba, J.; Bryja, Josef; Burda, H.

    2012-01-01

    Roč. 57, č. 2 (2012), s. 121-130 ISSN 0001-7051 R&D Projects: GA AV ČR IAA601410802 Institutional research plan: CEZ:AV0Z60930519 Keywords : Fukomys mechowii * subterranean rodent * burrow system * kin structure * Bathyergidae Subject RIV: EG - Zoology Impact factor: 0.949, year: 2012

  8. Poikilothermic traits in Mashona mole-rat (Fukomys darlingi). Reality or myth?

    Czech Academy of Sciences Publication Activity Database

    Zemanová, Milada; Šumbera, R.; Okrouhlík, J.

    2012-01-01

    Roč. 37, č. 7 (2012), s. 485-489 ISSN 0306-4565 Institutional support: RVO:60077344 Keywords : subterranean rodent * Bathyergidae * poikilothermy Subject RIV: ED - Physiology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 1.376, year: 2012 http://www.sciencedirect.com/science/article/pii/S0306456512000824

  9. The banded karyotype of the 2n=58 chromosomal race of mole rats from Erzincan, Turkey

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Zima, Jan

    2013-01-01

    Roč. 62, č. 1 (2013), s. 19-23 ISSN 0139-7893 Institutional support: RVO:68081766 Keywords : Ag-NOR staining * C-banding * Nannospalax xanthodon Subject RIV: EG - Zoology Impact factor: 0.741, year: 2013 http://hdl.handle.net/11104/0221259

  10. Review of chromosome races in blind mole rats (Spalax and Nannospalax)

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Kryštufek, B.; Matur, F.; Zima, Jan

    2016-01-01

    Roč. 65, č. 4 (2016), s. 249-301 ISSN 0139-7893 Institutional support: RVO:68081766 Keywords : karyotype * evolution * cytotypes * speciation Subject RIV: EG - Zoology Impact factor: 0.739, year: 2016

  11. Kinship structure and mating system in a solitary subterranean rodent, the silvery mole-rat

    Czech Academy of Sciences Publication Activity Database

    Patzenhauerová, Hana; Bryja, Josef; Šumbera, R.

    2010-01-01

    Roč. 64, č. 5 (2010), s. 757-767 ISSN 0340-5443 R&D Projects: GA AV ČR IAA601410802 Institutional research plan: CEZ:AV0Z60930519 Keywords : subterranean rodent * kinship structure * mating system * dispersal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.565, year: 2010

  12. The reproductive biology of the giant Zambian mole-rat, Cryptomys ...

    African Journals Online (AJOL)

    Cryptomys mechowi occurs in the mesic Miombo tropical woodland and savanna of Zambia, Zaïre and Angola. It is a colonial balhyergid in which reproduction is restricted lo a single female. Courtship and copulation are initiated by the female. Copulation is brief and does not involve multiple bouts. The gestation length is ...

  13. Seismic communication in demon African mole rat Tachyoryctes daemon from Tanzania

    Czech Academy of Sciences Publication Activity Database

    Hrouzková, E.; Dvořáková, V.; Jedlička, Petr; Šumbera, R.

    2013-01-01

    Roč. 31, č. 3 (2013), s. 255-259 ISSN 0289-0771 Institutional support: RVO:67985530 Keywords : seismic communication * substrate-borne vibration * subterranean mammal Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 0.790, year: 2013

  14. Oxygen-Binding Characteristics of Hemoglobins from Hypoxia and Hypercapnia Tolerant African Mole Rats

    DEFF Research Database (Denmark)

    Weber, Roy E.; Jarvis, Jennifer U. M; Fago, Angela

    2016-01-01

    ) originating from a range of different biomes and soil types. The study shows no evidence for distinguishing interspecific differences in hematological characters (e.g. DPG and Hb levels and isoHb differentiation). Additionally small differences observed in Hb’s intrinsic O2 affinity and in the effects of p...

  15. The chromosome banding pattern in two cytotypes (2n = 36 and 38) of blind mole rats from Turkey (Mammalia: Spalaxidae)

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Arisoy, A.; Zima, Jan

    2013-01-01

    Roč. 59, č. 2 (2013), s. 95-100 ISSN 0939-7140 Institutional support: RVO:68081766 Keywords : Nannospalax xanthodon * Ag-NOR staining * C-banding * Aydin * Manisa * western Anatolia Subject RIV: EG - Zoology Impact factor: 0.524, year: 2013

  16. Phylogeny of species and cytotypes of mole rats (Spalacidae) in Turkey inferred from mitochondrial cytochrome b gene sequencees

    Czech Academy of Sciences Publication Activity Database

    Kandemir, I.; Sozen, M.; Matur, F.; Kankilic, T.; Martínková, Natália; Colak, F.; Ozkurt, S. O.; Colak, E.

    2012-01-01

    Roč. 61, č. 1 (2012), s. 25-33 ISSN 0139-7893 Institutional support: RVO:68081766 Keywords : Nannospalax * molecular phylogeny * chromosomal form * Anatolia * Thrace Subject RIV: EG - Zoology Impact factor: 0.494, year: 2012

  17. Burrow systems of mole-rats as refuges for frogs in the Miombo woodlands of south-east Africa

    Czech Academy of Sciences Publication Activity Database

    Šklíba, J.; Jirků, Miloslav; Šumbera, R.

    2016-01-01

    Roč. 32, MAR (2016), s. 158-161 ISSN 0266-4674 R&D Projects: GA ČR GB14-36098G Institutional support: RVO:60077344 Keywords : aestivation * Anura * Bathyergidae * commensalism * ecosystem engineer * Malawi * subterranean rodent * Zambia Subject RIV: EG - Zoology Impact factor: 1.041, year: 2016

  18. The visual system in subterranean African mole-rats (Rodentia, Bathyergidae): Retina, subcortical visual nuclei and primary visual cortex

    Czech Academy of Sciences Publication Activity Database

    Němec, P.; Cveková, P.; Benada, Oldřich; Wielkopolska, E.; Olkowitz, S.; Turlejski, K.; Burda, H.; Bennett, N. C.; Peichl, L.

    2008-01-01

    Roč. 75, 2-4 (2008), s. 356-364 ISSN 0361-9230 Grant - others:GA AV ČR(CZ) GA206/06/1469; ZA(ZA) 2069070 Institutional research plan: CEZ:AV0Z50200510 Keywords : microphthalmia * ocular regression * subterranean mammals Subject RIV: EE - Microbiology, Virology Impact factor: 2.281, year: 2008

  19. Transcriptome sequencing of the blind subterranean mole rat, Spalax galili: Utility and potential for the discovery of novel evolutionary patterns

    KAUST Repository

    Malik, Assaf; Korol, Abraham; Hü bner, Sariel; Hernandez, Alvaro G.; Thimmapuram, Jyothi; Ali, Shahjahan; Glaser, Fabian; Paz, Arnon; Avivi, Aaron; Band, Mark

    2011-01-01

    sequencing of Spalax galili, a chromosomal type of S. ehrenbergi. cDNA pools from muscle and brain tissues isolated from animals exposed to hypoxic and normoxic conditions were sequenced using Sanger, GS FLX, and GS FLX Titanium technologies. Assembly

  20. The Predictive Power of Evolutionary Biology and the Discovery of Eusociality in the Naked Mole-Rat.

    Science.gov (United States)

    Braude, Stanton

    1997-01-01

    Discusses how biologists use evolutionary theory and provides examples of how evolutionary biologists test hypotheses on specific modes of selection and evolution. Presents an example of the successful predictive power of one evolutionary hypothesis. Contains 38 references. (DDR)

  1. A maze-lover's dream: Burrow architecture, natural history and habitat characteristics of Ansell's mole-rat (Fukomys anselli)

    Czech Academy of Sciences Publication Activity Database

    Šklíba, J.; Mazoch, V.; Patzenhauerová, Hana; Hrouzková, E.; Lövy, M.; Kott, O.; Šumbera, R.

    2012-01-01

    Roč. 77, č. 6 (2012), s. 420-427 ISSN 1616-5047 R&D Projects: GA AV ČR IAA601410802 Institutional support: RVO:68081766 Keywords : Bathyergidae * Burrow system * Sociality * Habitat characteristics * Subterranean mammal * Fukomys anselli Subject RIV: EG - Zoology Impact factor: 1.246, year: 2012

  2. Variation in C-heterochromatin and NOR distribution among chromosomal races of mole rats (Spalacidae) from Central Anatolia,Turkey

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Sükrüye, A.; Zima, Jan

    2011-01-01

    Roč. 76, č. 1 (2011), s. 28-35 ISSN 1616-5047 R&D Projects: GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : Nannospalax nehringi * Karyotype evolution * Speciation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.609, year: 2011

  3. Spatial variability of soil electrical conductivity under the mole rats (Spalax microphthalmus digging activity at the different scales

    Directory of Open Access Journals (Sweden)

    A. V. Zhukov

    2012-07-01

    Full Text Available The soil mounds emerged owing to the mole rats’ digging activity have been shown to be characterised by less electrical conductivity than surrounded soil. This effect is due to the changes of the mounds bulk’s density and moisture. The effect of the mole rats’ digging activity on the soil electrical conductivity has been found not to be restricted by the geometrical border of the mounds. The mounds are surrounded by 1–1.5 m halo of increased soil electrical conductivity. The halo size is increased with the aging of the mound and with the compacting of their aggregation.

  4. Regulation of Gene Expression by DNA Methylation and RNA Editing in Animals

    DEFF Research Database (Denmark)

    Li, Qiye

    , there has been growing interest in exploring the modifications occurring at the RNA level, which can impact the fate and function of mRNA. One fascinating type of such modifications is RNA editing, which alters specific nucleotides in transcribed RNA and thus can produce transcripts that are not encoded...... (Heterocephalus glaber), a eusocial mammal living in cooperative colonies. Finally, I introduce a software package that I developed that is specifically designed for the genome-wide identification of RNA-editing sites in animals, with the ultimate aim of promoting the evolutionary and functional study of RNA...... editing in different species....

  5. Incisors as digging tools in molerats (Bathyergidae)

    African Journals Online (AJOL)

    1998-03-26

    Xa and Vb) at which the upper and lower incisors (lines a- ..... JARVIS. JU.M., BENNETT. N.C. 1991. Introducing the Alriean mole-rats (family Bathyergidae). In: The biology of the naked mole-rat: 66 - 96. (Eds) Sherman. R. W ..

  6. Field evidence for colony size and aseasonality of breeding and in ...

    African Journals Online (AJOL)

    Ansell's mole-rat, Fukomys anselli, is a cooperatively breeding bathyergid endemic to the Lusaka Province of Zambia. During a 12-month field study involving the capture of 33 colonies of mole-rats, the number of occupants, breeding females and sex ratio within colonies were recorded. While thirty of these social groups ...

  7. Stemcell Information: SKIP000887 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available NICATIONS 2015 7 11471 ... http://www.ncbi.nlm.nih.gov/pubmed/27161380 ... ...Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Shingo Miyawaki, Hideyuki Okano et al. NATURE COMMU

  8. Animal remains of the Neolithic Ritual Burial Complex near Krum Village (Haskovo Region, SE Bulgaria

    Directory of Open Access Journals (Sweden)

    Zlatozar Boev

    2014-10-01

    Full Text Available From a total of 389 highly fragmented animal bone and tooth finds, dated ca. 6500-6300 B.P. have been identified 7 taxa: Lesser mole rat, Eurasian beaver, Cattle, Sheep, Goat, Pig, and Donkey.

  9. Chromosome banding pattern retrieves an independent origin of 2n = 50 chromosome populations of Nannospalax xanthodon from Turkey

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Zima, Jan

    2015-01-01

    Roč. 80, č. 5 (2015), s. 440-445 ISSN 1616-5047 Institutional support: RVO:68081766 Keywords : Karyotype * Chromosomal races * Mole rats * Anatolia Subject RIV: EG - Zoology Impact factor: 1.595, year: 2015

  10. Seasonal variation in plasma and corpus luteum oestradiol.17[3and ...

    African Journals Online (AJOL)

    Flemming 1993) and, in males, with circulating sex steroid concentrations ..... biology of the Cape mole-rat, Georychus capensis (Rodentia. Bathycrgidac), j, Zool" ... brain. and behavior: an emerging discipline in herpetology. In: Biology of the ...

  11. Proč rypoši nestárnou?

    OpenAIRE

    Jelínková, Alena

    2016-01-01

    Naked mole rat and blind mole rat are useful model organisms for human age-associated diaseases studies. Unlike human, their long lifespan is not accompanied by physical health impairment. In both species, the genes involved in aging process or carcinogenesis are under positive selection or their regulation differs from the regulatory pattern known in other rodents or human. Some genes are present in higher number of copies, missing or entirely new and not observed in other organisms. In nake...

  12. Light perception in two strictly subterranean rodents: life in the dark or blue?

    Directory of Open Access Journals (Sweden)

    Ondrej Kott

    Full Text Available BACKGROUND: The African mole-rats (Bathyergidae, Rodentia are strictly subterranean, congenitally microphthalmic rodents that are hardly ever exposed to environmental light. Because of the lack of an overt behavioural reaction to light, they have long been considered to be blind. However, recent anatomical studies have suggested retention of basic visual capabilities. In this study, we employed behavioural tests to find out if two mole-rat species are able to discriminate between light and dark, if they are able to discriminate colours and, finally, if the presence of light in burrows provokes plugging behaviour, which is assumed to have a primarily anti-predatory function. METHODOLOGY/PRINCIPAL FINDING: We used a binary choice test to show that the silvery mole-rat Heliophobius argenteocinereus and the giant mole-rat Fukomys mechowii exhibit a clear photoavoidance response to full-spectrum ("white", blue and green-yellow light, but no significant reaction to ultraviolet or red light during nest building. The mole-rats thus retain dark/light discrimination capabilities and a capacity to perceive short to medium-wavelength light in the photopic range of intensities. These findings further suggest that the mole-rat S opsin has its absorption maximum in the violet/blue part of the spectrum. The assay did not yield conclusive evidence regarding colour discrimination. To test the putative role of vision in bathyergid anti-predatory behaviour, we examined the reaction of mole-rats to the incidence of light in an artificial burrow system. The presence of light in the burrow effectively induced plugging of the illuminated tunnel. CONCLUSION/SIGNIFICANCE: Our findings suggest that the photopic vision is conserved and that low acuity residual vision plays an important role in predator avoidance and tunnel maintenance in the African mole-rats.

  13. Flower color changes in three Japanese hibiscus species: further quantitative variation of anthocyanin and flavonols.

    Science.gov (United States)

    Shimokawa, Satoshi; Iwashina, Tsukasa; Murakami, Noriaki

    2015-03-01

    One anthocyanin and four flavonols were detected from the petals of Hibiscus hamabo, H. tiliaceus and H. glaber. They were identified as cyanidin 3-0- sambubioside, gossypetin 3-O-glucuronide-8-O-glucoside, quercetin 7-O-rutinoside, gossypetin 3-O-glucoside and gossypetin 8-O-glucuronide by UV spectra, LC-MS, acid hydrolysis and HPLC. The flavonoid composition was essentially the same among the petals ofH. hamabo, H. tiliaceus and H. glaber, and there was little quantitative variation, except for cyanidin 3-O-sambubioside, the content of which in the petals ofH. tiliaceus and H. glaber was much higher than in that of H. hamabo. Flower colors of H. tiliaceus and H. glaber change from yellow to red, and that of H. hamabo changes from yellow to orange. These changes were caused by contents of anthocyanin and flavonols, which increased after flowering of H. hamabo, H. tiliaceus and H. glaber.

  14. Heterochromatin distribution and localization of NORs in the 2n = 48 cytotypes of Nannospalax xanthodon and N. ehrenbergi

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Zima, Jan

    2017-01-01

    Roč. 41, č. 3 (2017), s. 390-396 ISSN 1300-0179 Institutional support: RVO:68081766 Keywords : karyotype * chromosomal races * mole rats * Anatolia * Turkey Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 0.785, year: 2016

  15. Possible modulatory effects of male cues and social system on ...

    African Journals Online (AJOL)

    ... circulating levels of luteinizing hormone (LH) and the response of the pituitary to an exogenous gonadotropin-releasing hormone (GnRH) challenge in two mole-rat species with induced ovulation but contrasting mating and social systems. Females were either kept in isolation, allowed only olfactory and auditory contact or ...

  16. The retina of Spalax ehrenbergi: novel histologic features supportive of a modified photosensory role.

    NARCIS (Netherlands)

    Cernuda-Cernuda, R.; Grip, W.J. de; Cooper, H.M.; Nevo, E.; Garcia-Fernandez, J.M.

    2002-01-01

    PURPOSE: The retina of the blind mole rat Spalax ehrenbergi was compared with other vertebrate photosensitive organs in an attempt to correlate its histologic organization with a presumptive nonvisual photoreceptor role. METHODS: The eyes of eight adult animals were analyzed by light and electron

  17. A new cytotype (2n=46) of Nannospalax xanthodon from Turkey

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Zima, Jan; Yorulmaz, T.; Arslan, E.

    2014-01-01

    Roč. 60, č. 4 (2014), s. 283-287 ISSN 0939-7140 Institutional support: RVO:68081766 Keywords : Mole rats * Chromosomes * C-banding * NOR staining * Osmaniye * Anatolia Subject RIV: EG - Zoology Impact factor: 0.411, year: 2014

  18. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Clipboard: Of pungency, pain, and naked mole rats: chili peppers revisited · Renee M Borges · More Details Fulltext PDF. Volume 34 Issue 4 October 2009 pp 605-611 Articles. Phenotypic plasticity and longevity in plants and animals: cause and effect? Renee M Borges · More Details Abstract Fulltext PDF. Immobile plants ...

  19. case of natural queen succession in a captive colony of naked mole ...

    African Journals Online (AJOL)

    Naked mole-rats occur in large colonies where usually a single queen monopolizes reproduction. Queen succession occurs from within usually as a result of aggressive encounters with subordinate females that queue for reproductive succession following colony instability, which inevitably results in death of either the ...

  20. An example of burrow system architecture of dispersing Damaraland ...

    African Journals Online (AJOL)

    The Damaraland mole-rat (Fukomys damarensis) is a social, subterranean rodent that occurs in the red Kalahari sands. This species exhibits extreme reproductive skew with a single breeding female whereas reproduction in subordinate group members is completely blocked. Rainfall, as it greatly facilitates burrowing, ...

  1. Ontogenetic variation and craniometric sexual dimorphism in the ...

    African Journals Online (AJOL)

    The degree of maxillary molar tooth-row eruption and wear were used to assign samples of the social giant mole-rat, Fukomys mechowii, from Zambia, into nine relative age classes in order to assess ontogenetic (age) variation and craniometric sexual dimorphism, with reference to body mass. Univariate and multivariate ...

  2. Life history comparison of two terrestrial isopods in relation to habitat specialization

    Science.gov (United States)

    Quadros, Aline Ferreira; Caubet, Yves; Araujo, Paula Beatriz

    2009-03-01

    For many animal species, there is a relationship between life history strategies, as predicted by the r- K-selection theory, degree of habitat specialization and response to habitat alteration and loss. Here we compare two sympatric woodlice species with contrasting patterns of habitat use and geographical distribution. We predict that Atlantoscia floridana (Philosciidae), considered a habitat generalist, would exhibit the r-selected traits, whereas Balloniscus glaber (Balloniscidae), considered a habitat specialist, should have the K-selected traits. We analyzed several life history traits as well as life and fecundity tables using 715 and 842 females of A. floridana and B. glaber, respectively, from populations living in syntopy in southern Brazil. As predicted, most evaluated traits allow A. floridana to be considered an r-strategist and B. glaber a K-strategist: A. floridana showed a shorter lifetime, faster development, earlier reproduction, a smaller parental investment, higher net reproductive rate ( R0), a higher growth rate ( r) and a shorter generation time ( T) in comparison to B. glaber. A. floridana seems to be a successful colonizer with a high reproductive output. These characteristics explain its local abundance, commonness and wide geographical distribution. On the contrary, B. glaber has a restricted geographical distribution that is mainly associated with Atlantic forest fragments, a biome threatened by deforestation and replacement by monocultures. Its narrow distribution combined with the K-selected traits may confer to this species an increased extinction risk.

  3. Molecular and Physiological Factors of Neuroprotection in Hypoxia-tolerant Models: Pharmacological Clues for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Thomas I. Nathaniel

    2015-01-01

    Full Text Available The naked mole-rat possesses several unique physiological and molecular features that underlie their remarkably and exceptional resistance to tissue hypoxia. Elevated pattern of Epo, an erythropoietin (Epo factor; c-fos; vascular endothelial growth factor (VEGF; and hypoxia-inducible factors (HIF-1α contribute to the adaptive strategy to cope with hypoxic stress. Moreover, the naked mole-rat has a lower metabolic rate than any other eutherian mammal of comparable size that has been studied. The ability to actively reduce metabolic rate represents a strategy widely used in the face of decreased tissue oxygen availability. Understanding the different molecular and physiological factors that induce metabolic suppression could guide the development of pharmacological agents for the clinical management of stroke patient.

  4. Vibrational communication of subterranean rodents

    OpenAIRE

    HROUZKOVÁ, Ema

    2012-01-01

    This PhD. thesis focuses on the vibrational communication of subterranean mammals, in particular, vocal communication of bathyergids (Heliophobius argenteocinereus, Fukomys mechowii, Fukomys darlingi) and seismic communication of Tachyoryctes. We recorded and analyzed the vocalization of three species and discussed the physical parameters of their vocalization in relationship to the special underground acoustic environment. Moreover, social systems of African mole-rats range from solitary to ...

  5. Seismic communication in a blind subterranean mammal: a major somatosensory mechanism in adaptive evolution underground.

    OpenAIRE

    Nevo, E; Heth, G; Pratt, H

    1991-01-01

    Seismic communication, through low-frequency and patterned substrate-borne vibrations that are generated by head thumping, and which travel long distances underground, is important in the nonvisual communication of subterranean mole rats of the Spalax ehrenbergi superspecies (2n = 52, 54, 58, and 60) in Israel. This importance pertains both intraspecifically in adaptation and interspecifically in speciation. Neurophysiologic, behavioral, and anatomic findings in this study suggest that the me...

  6. Cellular Basis for Learning Impairment in Fragile X Syndrome

    Science.gov (United States)

    2014-08-01

    advances in therapy for neurological conditions such as stroke and epilepsy. KEY WORDS: Arctic ground squirrel, Cetacean, Hypoxia, Naked mole-rat...including migration and hibernation. Oxygen levels also vary widely, with animals adapted to sea level, high-altitude, underground and aquatic habitats...adapted for life in specific ecological niches as well as inform advances in therapy for neurological conditions such as stroke and epilepsy. Down for

  7. Florae Malesianae Precursores III. Dialium L. (Caesalpiniaceae)

    NARCIS (Netherlands)

    Wit, de H.C.D.

    1953-01-01

    Dialium hydnocarpoides, sp. nov. — Foliola (15)17—19, elliptice oblonga, 4.5—6.5(8.5) cm longa, 2—2.5(3) cm lata, apice abrupte breviter acuminata. Sepala extus pubescentia, intus puberula. Stamina 2, raro 3. Ovarium in receptaculo plano, lato, strigoso excentrice insertum. Stylus glaber. Legumen

  8. Attempted molecular detection of the thermally dimorphic human fungal pathogen Emergomyces africanus in terrestrial small mammals in South Africa.

    Science.gov (United States)

    Cronjé, Nadine; Schwartz, Ilan S; Retief, Liezl; Bastos, Armanda D S; Matthee, Sonja; Preiser, Wolfgang; Bennett, Nigel C; Maphanga, Tsidiso; Govender, Nelesh P; Colebunders, Robert; Kenyon, Chris

    2018-06-01

    The ecological niche of Emergomyces africanus (formerly Emmonsia species), a dimorphic fungus that causes an AIDS-related mycosis in South Africa, is unknown. We hypothesized that natural infection with E. africanus occurs in wild small mammals. Using molecular detection with primers specific for E. africanus, we examined 1402 DNA samples from 26 species of mole-rats, rodents, and insectivores trapped in South Africa that included 1324 lung, 37 kidney, and 41 liver specimens. DNA of E. africanus was not detected in any animals. We conclude that natural infection of wild small mammals in South Africa with E. africanus has not been proven.

  9. Mapping Ad Hoc Communications Network of a Large Number Fixed-Wing UAV Swarm

    Science.gov (United States)

    2017-03-01

    shows like "Agents of S.H.I.E.L.D". Inspiration can come from the imaginative minds of people or from the world around us. Swarms have demonstrated a...high degree of success. Bees , ants, termites, and naked mole rats maintain large groups that distribute tasks among individuals in order to achieve...the application layer and not the transport layer. Real- world vehicle-to-vehicle packet delivery rates for the 50-UAV swarm event were de- scribed in

  10. Consideraciones taxonómicas en especies de Senecio de Argentina Taxonomic considerations on Argentine species of Senecio

    Directory of Open Access Journals (Sweden)

    Roberto D. Tortosa

    2010-12-01

    Full Text Available Se incluyen algunas especies de Senecio de Argentina, reconocidas hasta el presente como especies válidas, en la sinonimia de otras: S. francisci Phil. en S. polygaloides Phil.; S. gymnocaulos Phil. en S. kingii Hook. f.; S. molinae Phil. en S. glaber Less.; S. mustersii Speg. y su var. dentatus Cabrera en S. subumbellatus Phil. Senecio microcephalus Phil. y su var. angustifolius Cabrera son consideradas una variedad de S. subumbellatus y S. schreiteri Cabrera una variedad de S. leucostachys Baker. No se acepta la validez de las variedades Senecio gilliesii Hook. et Arn. var. dasycarpus Cabrera, S. glaber Less. var. pratensis (Phil. Cabrera, S. gnidioides Phil. var. gilvus (Phil. Cabrera, S. kingii Hook. f. var. paradoxus (Albov ex Kurtz Cabrera, S. leucomallus A. Gray var. incisus A. Gray, S. linariifolius Poepp. ex DC. var. heliophytoides (Phil. Reiche y var. subtomentosus Cabrera y de la forma S. perezii Cabrera fo. integerrimus Cabrera.

  11. Diversity and population characteristics of terrestrial isopods (Crustacea, Oniscidea across three forest environments in southern Brazil

    Directory of Open Access Journals (Sweden)

    Priscila da Silva Bugs

    2014-09-01

    Full Text Available Terrestrial isopods are important and dominant component of meso and macrodecomposer soil communities. The present study investigates the diversity and species composition of terrestrial isopods on three forests on the Serra Geral of the state of Rio Grande do Sul, Brazil. The area has two natural formations (Primary Woodland and Secondary Woodland and one plantation of introduced Pinus. The pitfall traps operated from March 2001 to May 2002, with two summer periods and one winter. There were 14 sampling dates overall. Of the five species found: Alboscia silveirensis Araujo, 1999, Atlantoscia floridana (van Name, 1940, Benthana araucariana Araujo & Lopes, 2003 (Philoscidae, Balloniscus glaber Araujo & Zardo, 1995 (Balloniscidae and Styloniscus otakensis (Chilton, 1901 (Styloniscidae; only A. floridana is abundant on all environments and B. glaber is nearly exclusive for the native forests. The obtained data made it possible to infer about population characteristics of this species. The Similarity Analysis showed a quantitative difference among the Secondary forest and Pinus plantation, but not a qualitative one. The operational sex ratio (OSR analysis for A. floridana does not reveal significant differences in male and female proportions among environments. The reproductive period identified in the present study for A. floridana was from spring to autumn in the primary forest and Pinus plantation and during all year for the secondary forest. The OSR analysis for B. glaber reveals no significant differences in abundance between males and females for secondary forest, but the primary forest was a significant difference. The reproductive period for B. glaber extended from summer to autumn (for primary and secondary forest. This is the first record for Brazil of an established terrestrial isopod population in a Pinus sp. plantation area, evidenced by the presence of young, adults and ovigerous females, balanced sex ratio, expected fecundity and

  12. First record of Wolbachia in South American terrestrial isopods: prevalence and diversity in two species of Balloniscus (Crustacea, Oniscidea

    Directory of Open Access Journals (Sweden)

    Mauricio Pereira Almerão

    2012-01-01

    Full Text Available Wolbachia are endosymbiotic bacteria that commonly infect arthropods, inducing certain phenotypes in their hosts. So far, no endemic South American species of terrestrial isopods have been investigated for Wolbachia infection. In this work, populations from two species of Balloniscus (B. sellowii and B. glaber were studied through a diagnostic PCR assay. Fifteen new Wolbachia 16S rDNA sequences were detected. Wolbachia found in both species were generally specific to one population, and five populations hosted two different Wolbachia 16S rDNA sequences. Prevalence was higher in B. glaber than in B. sellowii, but uninfected populations could be found in both species. Wolbachia strains from B. sellowii had a higher genetic variation than those isolated from B. glaber. AMOVA analyses showed that most of the genetic variance was distributed among populations of each species rather than between species, and the phylogenetic analysis suggested that Wolbachia strains from Balloniscus cluster within Supergroup B, but do not form a single monophyletic clade, suggesting multiple infections for this group. Our results highlight the importance of studying Wolbachia prevalence and genetic diversity in Neotropical species and suggest that South American arthropods may harbor a great number of diverse strains, providing an interesting model to investigate the evolution of Wolbachia and its hosts.

  13. Efficiency of producing anion and relative humidity of the indigenous woody plants in Jeju islands

    Science.gov (United States)

    Son, S.-G.; Kim, K.-J.; Kim, H.-J.; Kim, C.-M.; Byun, K.-O.

    2009-04-01

    This study is to evaluate the ability of interior plants to produce anion and relative humidity that can purify polluted indoor air. Four indigenous woody plants in Jeju islands such as Sarcandra glaber (Thunb.) Nakai, Illicium anisatum L, Cleyera japonica Thunb. and Ilex rotunda Thunb. were used. Sansevieria trifasciata cv. Laurentii was also used as a comparative plant. The amount of anion and increment of relative humidity produced by five species of indoor plants was assessed by anion measurement (ITC-201A)in a sealed acryl chamber (118Ã-118Ã-119.5cm). The highest amount of anion was 515 ea/cm3produced by I. rotunda. The amounts of anion were 293 ea/cm3, 273 ea/cm3, and 211 ea/cm3 in S. glaber, I. anisatum and C. japonica, respecively while it was 220 ea/cm3 in S. trifasciata. The increment of relative humidity was highest in I. anisatum as 27.4% while it was lowest in S. trifasciata as 14.0%. This result suggested that all four indigenous plants tested were more effective to purify the indoor polluted air than S. trifasciata. Key words: interior plant, S. glaber, I. anisatum, C. japonica, I. rotunda, indoor polluted air

  14. A Trickster in Disguise: Hyaluronan’s Ambivalent Roles in the Matrix

    Directory of Open Access Journals (Sweden)

    Lena Bohaumilitzky

    2017-10-01

    Full Text Available Hyaluronan (HA is a simple but diverse glycosaminoglycan. It plays a major role in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA affects the surrounding tissues greatly depends on the molecular weight of HA. Whereas high molecular weight HA is associated with homeostasis and protective effects, HA fragments tend to be linked to the pathologic state. Furthermore, the interaction of HA with its binding partners, the hyaladherins, such as CD44, is essential for sustaining tissue integrity and is likewise related to cancer. The naked mole rat, a rodent species, possesses a special form of very high molecular weight (vHMW HA, which is associated with the extraordinary cancer resistance and longevity of those animals. This review addresses HA and its diverse facets: from HA synthesis to degradation, from oligomeric HA to vHMW-HA and from its beneficial properties to the involvement in pathologies. We further discuss the functions of HA in the naked mole rat and compare them to human conditions. Though intensively researched, this simple polymer bears some secrets that may hold the key for a better understanding of cellular processes and the development of diseases, such as cancer.

  15. Sex- and brain region-specific patterns of gene expression associated with socially-mediated puberty in a eusocial mammal.

    Directory of Open Access Journals (Sweden)

    Mariela Faykoo-Martinez

    Full Text Available The social environment can alter pubertal timing through neuroendocrine mechanisms that are not fully understood; it is thought that stress hormones (e.g., glucocorticoids or corticotropin-releasing hormone influence the hypothalamic-pituitary-gonadal axis to inhibit puberty. Here, we use the eusocial naked mole-rat, a unique species in which social interactions in a colony (i.e. dominance of a breeding female suppress puberty in subordinate animals. Removing subordinate naked mole-rats from this social context initiates puberty, allowing for experimental control of pubertal timing. The present study quantified gene expression for reproduction- and stress-relevant genes acting upstream of gonadotropin-releasing hormone in brain regions with reproductive and social functions in pre-pubertal, post-pubertal, and opposite sex-paired animals (which are in various stages of pubertal transition. Results indicate sex differences in patterns of neural gene expression. Known functions of genes in brain suggest stress as a key contributing factor in regulating male pubertal delay. Network analysis implicates neurokinin B (Tac3 in the arcuate nucleus of the hypothalamus as a key node in this pathway. Results also suggest an unappreciated role for the nucleus accumbens in regulating puberty.

  16. Living in a ``stethoscope'': burrow-acoustics promote auditory specializations in subterranean rodents

    Science.gov (United States)

    Lange, Simone; Burda, Hynek; Wegner, Regina E.; Dammann, Philip; Begall, Sabine; Kawalika, Mathias

    2007-02-01

    Subterranean mammals rely to a great extent on audition for communication and to be alerted to danger. The only hitherto published report on burrow acoustics revealed that in tunnels of blind mole-rats ( Spalax ehrenbergi), airborne sounds of 440 Hz propagated best whereas lower and higher frequencies were effectively attenuated. Morpho-functional analyses classify the ear of subterranean mammals as a low-sensitivity and low-frequency device. Concordantly, hearing is characterized by low sensitivity and a restricted frequency range tuned to low frequencies (0.5-4 kHz). Some authors considered the restricted hearing in subterranean mammals vestigial and degenerate due to under-stimulation. In contrast to this view stand a rich (mostly low-frequency) vocal repertoire and progressive structural specializations of the middle and inner ear. Thus, other authors considered these hearing characteristics adaptive. To test the hypothesis that acoustical environment in burrows of different species of subterranean mammals is similar, we measured sound attenuation in burrows of Fukomys mole-rats (formerly known as Cryptomys, cf. Kock et al. 2006) of two differently sized species at different locations in Zambia. We show that in these burrows, low-frequency sounds (200-800 Hz) are not only least attenuated but also their amplitude may be amplified like in a stethoscope (up to two times over 1 m). We suggest that hearing sensitivity has decreased during evolution of subterranean mammals to avoid over-stimulation of the ear in their natural environment.

  17. Region-specific associations between sex, social status, and oxytocin receptor density in the brains of eusocial rodents.

    Science.gov (United States)

    Mooney, S J; Coen, C W; Holmes, M M; Beery, A K

    2015-09-10

    Naturally occurring variations in neuropeptide receptor distributions in the brain contribute to numerous mammalian social behaviors. In naked mole-rats, which live in large social groups and exhibit remarkable reproductive skew, colony-related social behaviors vary with reproductive status. Here we examined whether variation in social status is associated with variations in the location and/or density of oxytocin binding in this species. Autoradiography was performed to assess forebrain oxytocin receptor (OTR) densities in breeding and non-breeding naked mole-rats of both sexes. Overall, males exhibited higher OTR binding in the medial amygdala in comparison to females. While there were no main effects of reproductive status in any region, a sex difference in OTR binding in the nucleus accumbens was mediated by status. Specifically, breeding males tended to have more OTR binding than breeding females in the nucleus accumbens, while no sex difference was observed in subordinates. These effects suggest that oxytocin may act in a sex- and region-specific way that corresponds to reproductive status and associated social behaviors. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. The role of host traits, season and group size on parasite burdens in a cooperative mammal.

    Directory of Open Access Journals (Sweden)

    Hermien Viljoen

    Full Text Available The distribution of parasites among hosts is often characterised by a high degree of heterogeneity with a small number of hosts harbouring the majority of parasites. Such patterns of aggregation have been linked to variation in host exposure and susceptibility as well as parasite traits and environmental factors. Host exposure and susceptibility may differ with sexes, reproductive effort and group size. Furthermore, environmental factors may affect both the host and parasite directly and contribute to temporal heterogeneities in parasite loads. We investigated the contributions of host and parasite traits as well as season on parasite loads in highveld mole-rats (Cryptomys hottentotus pretoriae. This cooperative breeder exhibits a reproductive division of labour and animals live in colonies of varying sizes that procreate seasonally. Mole-rats were parasitised by lice, mites, cestodes and nematodes with mites (Androlaelaps sp. and cestodes (Mathevotaenia sp. being the dominant ecto- and endoparasites, respectively. Sex and reproductive status contributed little to the observed parasite prevalence and abundances possibly as a result of the shared burrow system. Clear seasonal patterns of parasite prevalence and abundance emerged with peaks in summer for mites and in winter for cestodes. Group size correlated negatively with mite abundance while it had no effect on cestode burdens and group membership affected infestation with both parasites. We propose that the mode of transmission as well as social factors constrain parasite propagation generating parasite patterns deviating from those commonly predicted.

  19. Long-lived cancer-resistant rodents as new model species for cancer research

    Directory of Open Access Journals (Sweden)

    Jorge eAzpurua

    2013-01-01

    Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

  20. Spontaneous expression of magnetic compass orientation in an epigeic rodent: the bank vole, Clethrionomys glareolus

    Science.gov (United States)

    Oliveriusová, Ludmila; Němec, Pavel; Pavelková, Zuzana; Sedláček, František

    2014-07-01

    Magnetoreception has been convincingly demonstrated in only a few mammalian species. Among rodents, magnetic compass orientation has been documented in four species of subterranean mole rats and two epigeic (i.e. active above ground) species—the Siberian hamster and the C57BL/6J mouse. The mole rats use the magnetic field azimuth to determine compass heading; their directional preference is spontaneous and unimodal, and their magnetic compass is magnetite-mediated. By contrast, the primary component of orientation response is learned in the hamster and the mouse, but both species also exhibit a weak spontaneous bimodal preference in the natural magnetic field. To determine whether the magnetic compass of wild epigeic rodents features the same functional properties as that of laboratory rodents, we investigated magnetic compass orientation in the bank vole Clethrionomys glareolus (Cricetidae, Rodentia). The voles exhibited a robust spontaneous bimodal directional preference, i.e. built nests and slept preferentially along the north-south axis, and deflected their directional preference according to a shift in the direction of magnetic north, clearly indicating that they were deriving directional information from the magnetic field. Thus, bimodal, axially symmetrical directional choice seems to be a common feature shared by epigeic rodents. However, spontaneous directional preference in the bank vole appeared to be more pronounced than that reported in the hamster and the mouse. These findings suggest that bank voles are well suited for future studies investigating the adaptive significance and mechanisms of magnetic orientation in epigeic rodents.

  1. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance

    Directory of Open Access Journals (Sweden)

    Elliott Ferris

    2018-03-01

    Full Text Available The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.

  2. Spatial and seasonal variations of leaf area index (LAI) in subtropical secondary forests related to floristic composition and stand characters

    Science.gov (United States)

    Zhu, Wenjuan; Xiang, Wenhua; Pan, Qiong; Zeng, Yelin; Ouyang, Shuai; Lei, Pifeng; Deng, Xiangwen; Fang, Xi; Peng, Changhui

    2016-07-01

    Leaf area index (LAI) is an important parameter related to carbon, water, and energy exchange between canopy and atmosphere and is widely applied in process models that simulate production and hydrological cycles in forest ecosystems. However, fine-scale spatial heterogeneity of LAI and its controlling factors have yet to be fully understood in Chinese subtropical forests. We used hemispherical photography to measure LAI values in three subtropical forests (Pinus massoniana-Lithocarpus glaber coniferous and evergreen broadleaved mixed forests, Choerospondias axillaris deciduous broadleaved forests, and L. glaber-Cyclobalanopsis glauca evergreen broadleaved forests) from April 2014 to January 2015. Spatial heterogeneity of LAI and its controlling factors were analysed using geostatistical methods and the generalised additive models (GAMs) respectively. Our results showed that LAI values differed greatly in the three forests and their seasonal variations were consistent with plant phenology. LAI values exhibited strong spatial autocorrelation for the three forests measured in January and for the L. glaber-C. glauca forest in April, July, and October. Obvious patch distribution pattern of LAI values occurred in three forests during the non-growing period and this pattern gradually dwindled in the growing season. Stem number, crown coverage, proportion of evergreen conifer species on basal area basis, proportion of deciduous species on basal area basis, and forest types affected the spatial variations in LAI values in January, while stem number and proportion of deciduous species on basal area basis affected the spatial variations in LAI values in July. Floristic composition, spatial heterogeneity, and seasonal variations should be considered for sampling strategy in indirect LAI measurement and application of LAI to simulate functional processes in subtropical forests.

  3. A new species of Cladotanytarsus (Lenziella) from Oregon supports the systematic concept of the subgenus (Diptera: Chironomidae).

    Science.gov (United States)

    Puchalski, Mateusz; Giłka, Wojciech

    2017-05-18

    A new species of the genus Cladotanytarsus Kieffer, 1921 and the small subgenus Lenziella Kieffer, 1922 is described from Southern Oregon, USA. The adult male of C. (L.) glaber Giłka et Puchalski, sp. nov., featuring tibial lobes armed with dense setae and a large globular swelling of the hypopygial inferior volsella, supports the recently defined systematic concept for Lenziella. This subgenus is known from seven species distributed in the Northern Hemisphere (1 European, 1 Palaearctic and 5 Nearctic), the males of which are included in an updated identification key.

  4. Development of 12 genic microsatellite loci for a biofuel grass, Miscanthus sinensis (Poaceae).

    Science.gov (United States)

    Ho, Chuan-Wen; Wu, Tai-Han; Hsu, Tsai-Wen; Huang, Jao-Ching; Huang, Chi-Chun; Chiang, Tzen-Yuh

    2011-08-01

    Miscanthus, a nonfood plant with high potential as a biofuel, has been used in Europe and the United States. The selection of a cultivar with high biomass, photosynthetic efficiency, and stress resistance from wild populations has become an important issue. New genic microsatellite markers will aid the assessment of genetic diversity for different strains. Twelve polymorphic microsatellite markers derived from the transcriptome of Miscanthus sinensis fo. glaber were identified and screened on 80 individuals of M. sinensis. The number of alleles per locus ranged from 6 to 12, and the mean expected heterozygosity was 0.75. Cross-taxa transferability revealed that all loci can be applied to all varieties of M. sinensis, as well as the closely related species M. floridulus. These new genic microsatellite markers are useful for characterizing different traits in breeding programs or to select genes useful for biofuel.

  5. Roadside Survey of Ants on Oahu, Hawaii

    Science.gov (United States)

    Tong, Reina L.; Grace, J. Kenneth; Krushelnycky, Paul D.

    2018-01-01

    Hawaii is home to over 60 ant species, including five of the six most damaging invasive ants. Although there have been many surveys of ants in Hawaii, the last island-wide hand-collection survey of ants on Oahu was conducted in 1988–1994. In 2012, a timed hand-collection of ants was made at 44 sites in a systematic, roadside survey throughout Oahu. Ants were identified and species distribution in relation to elevation, precipitation and soil type was analyzed. To assess possible convenience sampling bias, 15 additional sites were sampled further from roads to compare with the samples near roads. Twenty-four species of ants were found and mapped; Pheidole megacephala (F.), Ochetellus glaber (Mayr), and Technomyrmex difficilis Forel were the most frequently encountered ants. For six ant species, a logistic regression was performed with elevation, average annual precipitation, and soil order as explanatory variables. O. glaber was found in areas with lower precipitation around Oahu. Paratrechina longicornis (Latrielle) and Tetramorium simillimum (Smith, F.) were found more often in lower elevations and in areas with the Mollisol soil order. Elevation, precipitation, and soil type were not significant sources of variation for P. megacephala, Plagiolepis alluaudi Emery, and T. difficilis. P. megacephala was associated with fewer mean numbers of ants where it occurred. Ant assemblages near and far from roads did not significantly differ. Many species of ants remain established on Oahu, and recent invaders are spreading throughout the island. Mapping ant distributions contributes to continued documentation and understanding of these pests. PMID:29439503

  6. Recovery of Physiological Traits in Saplings of Invasive Bischofia Tree Compared with Three Species Native to the Bonin Islands under Successive Drought and Irrigation Cycles.

    Science.gov (United States)

    Yazaki, Kenichi; Kuroda, Katsushi; Nakano, Takashi; Kitao, Mitsutoshi; Tobita, Hiroyuki; Ogasa, Mayumi Y; Ishida, Atsushi

    2015-01-01

    Partial leaf shedding induced by hydraulic failure under prolonged drought can prevent excess water consumption, resulting in delayed recovery of carbon productivity following rainfall. To understand the manner of water use of invasive species in oceanic island forests under a fluctuating water regime, leaf shedding, multiple physiological traits, and the progress of embolism in the stem xylem under repeated drought-irrigation cycles were examined in the potted saplings of an invasive species, Bischofia javanica Blume, and three endemic native species, Schima mertensiana (Sieb. Et Zucc,) Koitz., Hibiscus glaber Matsum, and Distylium lepidotum Nakai, from the Bonin Islands, Japan. The progress of xylem embolism was observed by cryo-scanning electron microscopy. The samples exhibited different processes of water saving and drought tolerance based on the different combinations of partial leaf shedding involved in embolized conduits following repeated de-rehydration. Predawn leaf water potential largely decreased with each successive drought-irrigation cycle for all tree species, except for B. javanica. B. javanica shed leaves conspicuously under drought and showed responsive stomatal conductance to VPD, which contributed to recover leaf gas exchange in the remaining leaves, following a restored water supply. In contrast, native tree species did not completely recover photosynthetic rates during the repeated drought-irrigation cycles. H. glaber and D. lepidotum preserved water in vessels and adjusted leaf osmotic rates but did not actively shed leaves. S. mertensiana exhibited partial leaf shedding during the first cycle with an osmotic adjustment, but they showed less responsive stomatal conductance to VPD. Our data indicate that invasive B. javanica saplings can effectively use water supplied suddenly under drought conditions. We predict that fluctuating precipitation in the future may change tree distributions even in mesic or moist sites in the Bonin Islands.

  7. Recovery of Physiological Traits in Saplings of Invasive Bischofia Tree Compared with Three Species Native to the Bonin Islands under Successive Drought and Irrigation Cycles.

    Directory of Open Access Journals (Sweden)

    Kenichi Yazaki

    Full Text Available Partial leaf shedding induced by hydraulic failure under prolonged drought can prevent excess water consumption, resulting in delayed recovery of carbon productivity following rainfall. To understand the manner of water use of invasive species in oceanic island forests under a fluctuating water regime, leaf shedding, multiple physiological traits, and the progress of embolism in the stem xylem under repeated drought-irrigation cycles were examined in the potted saplings of an invasive species, Bischofia javanica Blume, and three endemic native species, Schima mertensiana (Sieb. Et Zucc, Koitz., Hibiscus glaber Matsum, and Distylium lepidotum Nakai, from the Bonin Islands, Japan. The progress of xylem embolism was observed by cryo-scanning electron microscopy. The samples exhibited different processes of water saving and drought tolerance based on the different combinations of partial leaf shedding involved in embolized conduits following repeated de-rehydration. Predawn leaf water potential largely decreased with each successive drought-irrigation cycle for all tree species, except for B. javanica. B. javanica shed leaves conspicuously under drought and showed responsive stomatal conductance to VPD, which contributed to recover leaf gas exchange in the remaining leaves, following a restored water supply. In contrast, native tree species did not completely recover photosynthetic rates during the repeated drought-irrigation cycles. H. glaber and D. lepidotum preserved water in vessels and adjusted leaf osmotic rates but did not actively shed leaves. S. mertensiana exhibited partial leaf shedding during the first cycle with an osmotic adjustment, but they showed less responsive stomatal conductance to VPD. Our data indicate that invasive B. javanica saplings can effectively use water supplied suddenly under drought conditions. We predict that fluctuating precipitation in the future may change tree distributions even in mesic or moist sites in the

  8. Novel treatment strategies for chronic kidney disease: insights from the animal kingdom.

    Science.gov (United States)

    Stenvinkel, Peter; Painer, Johanna; Kuro-O, Makoto; Lanaspa, Miguel; Arnold, Walter; Ruf, Thomas; Shiels, Paul G; Johnson, Richard J

    2018-04-01

    Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

  9. The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

    Science.gov (United States)

    Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

    2015-07-19

    Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  10. Evaluating land use changes by landscape historical examinations at the great pasture of Hajdúbagos (Eastern Hungary

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    Zsuzsanna ANTAL

    2010-05-01

    Full Text Available At an Eastern Hungarian protected grassland, namely at the Lesser Mole Rat (Spalax leucodon Nordmann, 1840. Reservation of Hajdúbagos Nature Conservation Area, grazing animal husbandry formed the façade of the land for hundreds of years. Though, due to the unfavourable changes of the last few decades in this sector of agriculture, the primeval sand steppe meadow (Pulsatillo hungaricae-Festucetum rupicolae (Soó 1938 Borhidi 1996 plant association is endangered by the increasingly accelerating succession. To stop or at least to slow down this process the rehabilitation of the area could be necessary. The target of the restoration ecology actions is to restore the previously existing, more favourable natural status of a particular area. However, the lack of knowledge according to the conditions that refer to the original circumstances often complicates this activity. To define these reference conditions the exploration of the history of a certain landscape is very important as restoration is only successful if the restored ecosystem is similar to the original. We examined the land use changes of the research area during the last 250 years according to historical and present geographical databases using GIS technology and completed this work with the study of archival data. By our results we stated that these examinations are crucial in the proper - agriculture related - management of protected areas.

  11. The First International Mini-Symposium on Methionine Restriction and Lifespan

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    Gene eAbles

    2014-05-01

    Full Text Available It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met ingestion by rats extends lifespan [1]. Since then, several studies have replicated the effects of dietary methionine restriction (MR in delaying age-related diseases [2–5]. We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY last September 2013. The goals were 1 to gather researchers with an interest in methionine restriction and lifespan, 2 to exchange knowledge, 3 to generate ideas for future investigations, and 4 to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH, and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g. the naked mole rat, Brandt’s bat and drosophila in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

  12. High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

    Science.gov (United States)

    Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.

    2012-01-01

    Abstract Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA[Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185–192. PMID:21854231

  13. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance.

    Science.gov (United States)

    Ferris, Elliott; Abegglen, Lisa M; Schiffman, Joshua D; Gregg, Christopher

    2018-03-06

    The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Molecular cloning, sequence identification and expression profile of domestic guinea pig (Cavia porcellus UGT1A1 gene

    Directory of Open Access Journals (Sweden)

    Yang Deming

    2016-01-01

    Full Text Available Domestic guinea pig is a model animal for human disease research. Uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1 is an important human disease-related gene. In this study, the complete coding sequence of domestic guinea pig gene UGT1A1 was amplified by reverse transcription-polymerase chain reaction. The open reading frame of the domestic guinea pig UGT1A1 gene is 1602 bp in length and was found to encode a protein of 533 amino acids. Sequence analysis revealed that the UGT1A1 protein of domestic guinea pig shared high homology with the UGT1A1 proteins of degu (84%, damara mole-rat (84%, human (80%, northern white-cheeked gibbon (80%, Colobus angolensis palliatus (80% and golden snub-nosed monkey (79%. This gene contains five exons and four introns, as revealed by the computer-assisted analysis. The results also showed that the domestic guinea pig UGT1A1 gene had a close genetic relationship with the UGT1A1 gene of degu. The prediction of transmembrane helices showed that domestic guinea pig UGT1A1 might be a transmembrane protein. Expression profile analysis indicated that the domestic guinea pig UGT1A1 gene was differentially expressed in detected domestic guinea pig tissues. Our experiment laid a primary foundation for using the domestic guinea pig as a model animal to study the UGT1A1-related human diseases.

  15. The transcriptome of the bowhead whale Balaena mysticetus reveals adaptations of the longest-lived mammal

    Science.gov (United States)

    Seim, Inge; Ma, Siming; Zhou, Xuming; Gerashchenko, Maxim V.; Lee, Sang-Goo; Suydam, Robert; George, John C.; Bickham, John W.; Gladyshev, Vadim N.

    2014-01-01

    Mammals vary dramatically in lifespan, by at least two-orders of magnitude, but the molecular basis for this difference remains largely unknown. The bowhead whale Balaena mysticetus is the longest-lived mammal known, with an estimated maximal lifespan in excess of two hundred years. It is also one of the two largest animals and the most cold-adapted baleen whale species. Here, we report the first genome-wide gene expression analyses of the bowhead whale, based on the de novo assembly of its transcriptome. Bowhead whale or cetacean-specific changes in gene expression were identified in the liver, kidney and heart, and complemented with analyses of positively selected genes. Changes associated with altered insulin signaling and other gene expression patterns could help explain the remarkable longevity of bowhead whales as well as their adaptation to a lipid-rich diet. The data also reveal parallels in candidate longevity adaptations of the bowhead whale, naked mole rat and Brandt's bat. The bowhead whale transcriptome is a valuable resource for the study of this remarkable animal, including the evolution of longevity and its important correlates such as resistance to cancer and other diseases. PMID:25411232

  16. No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates

    Science.gov (United States)

    Larson, John; Drew, Kelly L.; Folkow, Lars P.; Milton, Sarah L.; Park, Thomas J.

    2014-01-01

    Many vertebrates are challenged by either chronic or acute episodes of low oxygen availability in their natural environments. Brain function is especially vulnerable to the effects of hypoxia and can be irreversibly impaired by even brief periods of low oxygen supply. This review describes recent research on physiological mechanisms that have evolved in certain vertebrate species to cope with brain hypoxia. Four model systems are considered: freshwater turtles that can survive for months trapped in frozen-over lakes, arctic ground squirrels that respire at extremely low rates during winter hibernation, seals and whales that undertake breath-hold dives lasting minutes to hours, and naked mole-rats that live in crowded burrows completely underground for their entire lives. These species exhibit remarkable specializations of brain physiology that adapt them for acute or chronic episodes of hypoxia. These specializations may be reactive in nature, involving modifications to the catastrophic sequelae of oxygen deprivation that occur in non-tolerant species, or preparatory in nature, preventing the activation of those sequelae altogether. Better understanding of the mechanisms used by these hypoxia-tolerant vertebrates will increase appreciation of how nervous systems are adapted for life in specific ecological niches as well as inform advances in therapy for neurological conditions such as stroke and epilepsy. PMID:24671961

  17. High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

    Energy Technology Data Exchange (ETDEWEB)

    Malinouski, M.; Kehr, S.; Finney, L.; Vogt, S.; Carlson, B.A.; Seravalli, J.; Jin, R.; Handy, D.E.; Park, T.J.; Loscalzo, J.; Hatfield, D.L.; Gladyshev, V.N. (Harvard-Med)

    2012-04-17

    Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.

  18. Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

    Directory of Open Access Journals (Sweden)

    Malik Assaf

    2012-11-01

    Full Text Available Abstract Background The development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research. Results Using microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals. Conclusions This is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to

  19. Taxonomic separation of hippocampal networks: principal cell populations and adult neurogenesis

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    Roelof Maarten evan Dijk

    2016-03-01

    Full Text Available While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippocampal function, because multiple taxonomic levels need to be considered to associate behavioral and anatomical changes. To provide information on anatomical changes within and across taxonomic ranks, we present a quantitative assessment of hippocampal principal cell populations in 20 species or strain groups, with emphasis on rodents, the taxonomic group that provides most animals used in laboratory research. Of special interest is the importance of adult hippocampal neurogenesis in species-specific adaptations relative to other cell populations. Correspondence analysis of cell numbers shows that across taxonomic units, phylogenetically related species cluster together, sharing similar proportions of principal cell populations. CA3 and hilus are strong separators that place rodent species into a tight cluster based on their relatively large CA3 and small hilus while non-rodent species (including humans and non-human primates are placed on the opposite side of the spectrum. Hilus and CA3 are also separators within rodents, with a very large CA3 and rather small hilar cell populations separating mole-rats from other rodents that, in turn, are separated from each other by smaller changes in the proportions of CA1 and granule cells. When adult neurogenesis is included, the relatively small populations of young neurons, proliferating cells and hilar neurons become main drivers of taxonomic separation within rodents. The observations provide challenges to the computational modeling of hippocampal function, suggest differences in the organization of hippocampal information streams in rodent and non

  20. Comparative endocrinology of aging and longevity regulation

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    John eAllard

    2011-11-01

    Full Text Available Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, regulate the aging process. Findings from the major model organisms: worms, flies and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms.

  1. Phylogeny and divergence-date estimates of rapid radiations in muroid rodents based on multiple nuclear genes.

    Science.gov (United States)

    Steppan, Scott; Adkins, Ronald; Anderson, Joel

    2004-08-01

    The muroid rodents are the largest superfamily of mammals, containing nearly one third of all mammal species. We report on a phylogenetic study comprising 53 genera sequenced for four nuclear genes, GHR, BRCA1, RAG1, and c-myc, totaling up to 6400 nucleotides. Most relationships among the subfamilies are resolved. All four genes yield nearly identical phylogenies, differing only in five key regions, four of which may represent particularly rapid radiations. Support is very strong for a fundamental division of the mole rats of the subfamilies Spalacinae and Rhizomyinae from all other muroids. Among the other "core" muroids, a rapid radiation led to at least four distinct lineages: Asian Calomyscus, an African clade of at least four endemic subfamilies, including the diverse Nesomyinae of Madagascar, a hamster clade with maximum diversity in the New World, and an Old World clade including gerbils and the diverse Old World mice and rats (Murinae). The Deomyinae, recently removed from the Murinae, is well supported as the sister group to the gerbils (Gerbillinae). Four key regions appear to represent rapid radiations and, despite a large amount of sequence data, remain poorly resolved: the base of the "core" muroids, among the five cricetid (hamster) subfamilies, within a large clade of Sigmodontinae endemic to South America, and among major geographic lineages of Old World Murinae. Because of the detailed taxon sampling within the Murinae, we are able to refine the fossil calibration of a rate-smoothed molecular clock and apply this clock to date key events in muroid evolution. We calculate rate differences among the gene regions and relate those differences to relative contribution of each gene to the support for various nodes. The among-gene variance in support is greatest for the shortest branches. We present a revised classification for this largest but most unsettled mammalian superfamily.

  2. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    Science.gov (United States)

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

  3. Life in groups: the roles of oxytocin in mammalian sociality

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    Allison eAnacker

    2013-12-01

    Full Text Available In recent decades, scientific understanding of the many roles of oxytocin in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that oxytocin influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of oxytocin to life in mammalian social groups. We provide background on the functions of oxytocin in maternal attachments and the early social environment, and give an overview of the role of oxytocin circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of oxytocin in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in oxytocin receptor levels with seasonal changes in social behavior in female meadow voles, and the effects of oxytocin manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that oxytocin is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. Oxytocin’s effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying friendships, organization of broad social structures, and maintenance of established social relationships with individuals

  4. Erotylidae (Insecta, Coleoptera of Poland – problematic taxa, updated keys and new records

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    Rafal Ruta

    2011-10-01

    Full Text Available New data concerning the occurrence of pleasing fungus beetles (Coleoptera: Erotylidae in Poland are given, with a focus on rare and difficult to identify Central European taxa. Cryptophilus cf. integer (Heer (Cryptophilinae is reported from the Polish territory for the first time based on adult and larval specimens collected in the Wielkopolska-Kujawy Lowland. Identification problems concerning species of Cryptophilus introduced to Europe are discussed. Triplax carpathica Reitter (Erotylinae is recorded from the Białowieża Primeval Forest, which is the first known non-Carpathian finding of this species, located in the close proximity of the Polish-Belarussian UNESCO World Heritage Site “Białowieża Forest”. Discussion of T. carpathica being conspecific with Siberian T. rufiventris Gebler is provided. New Polish localities of several other Erotylidae are reported, and an updated key to Central European species of Triplax is given. The Triplax key is supplemented with dorsal and ventral habitus images of all treated Triplax species. One of the rarest Central European erotyline species Combocerus glaber (Schaller is recorded from xerothermic grasslands in North-West Poland.

  5. Erotylidae (Insecta, Coleoptera) of Poland - problematic taxa, updated keys and new records.

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    Ruta, Rafał; Jałoszyński, Paweł; Sienkiewicz, Paweł; Konwerski, Szymon

    2011-01-01

    New data concerning the occurrence of pleasing fungus beetles (Coleoptera: Erotylidae) in Poland are given, with a focus on rare and difficult to identify Central European taxa. Cryptophilus cf. integer (Heer) (Cryptophilinae) is reported from the Polish territory for the first time based on adult and larval specimens collected in the Wielkopolska-Kujawy Lowland. Identification problems concerning species of Cryptophilus introduced to Europe are discussed. Triplax carpathica Reitter (Erotylinae) is recorded from the Białowieża Primeval Forest, which is the first known non-Carpathian finding of this species, located in the close proximity of the Polish-Belarussian UNESCO World Heritage Site "Białowieża Forest". Discussion of Triplax carpathica being conspecific with Siberian Triplax rufiventris Gebler is provided. New Polish localities of several other Erotylidae are reported, and an updated key to Central European species of Triplax is given. The Triplax key is supplemented with dorsal and ventral habitus images of all treated Triplax species. One of the rarest Central European erotyline species Combocerus glaber (Schaller) is recorded from xerothermic grasslands in North-West Poland.

  6. Erotylidae (Insecta, Coleoptera) of Poland – problematic taxa, updated keys and new records

    Science.gov (United States)

    Ruta, Rafał; Jałoszyński, Paweł; Sienkiewicz, Paweł; Konwerski, Szymon

    2011-01-01

    Abstract New data concerning the occurrence of pleasing fungus beetles (Coleoptera: Erotylidae) in Poland are given, with a focus on rare and difficult to identify Central European taxa. Cryptophilus cf. integer (Heer) (Cryptophilinae) is reported from the Polish territory for the first time based on adult and larval specimens collected in the Wielkopolska-Kujawy Lowland. Identification problems concerning species of Cryptophilus introduced to Europe are discussed. Triplax carpathica Reitter (Erotylinae) is recorded from the Białowieża Primeval Forest, which is the first known non-Carpathian finding of this species, located in the close proximity of the Polish-Belarussian UNESCO World Heritage Site “Białowieża Forest”. Discussion of Triplax carpathica being conspecific with Siberian Triplax rufiventris Gebler is provided. New Polish localities of several other Erotylidae are reported, and an updated key to Central European species of Triplax is given. The Triplax key is supplemented with dorsal and ventral habitus images of all treated Triplax species. One of the rarest Central European erotyline species Combocerus glaber (Schaller) is recorded from xerothermic grasslands in North-West Poland. PMID:22140339

  7. Genetic diversity and symbiotic compatibility among rhizobial strains and Desmodium incanum and Lotus spp. plants

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    Camille E Granada

    2014-06-01

    Full Text Available This work aimed to evaluate the symbiotic compatibility and nodulation efficiency of rhizobia isolated from Desmodium incanum, Lotus corniculatus, L. subbiflorus, L. uliginosus and L. glaber plants by cross-inoculation. Twelve reference strains and 21 native isolates of rhizobia were genetically analyzed by the BOX-PCR technique, which showed a high genetic diversity among the rhizobia studied. The isolates were also characterized based on their production of indolic compounds and siderophores, as well as on their tolerance to salinity. Fifteen of the 33 rhizobia analyzed were able to produce indolic compounds, whereas 13 produced siderophores. All the tested rhizobia were sensitive to high salinity, although some were able to grow in solutions of up to 2% NaCl. Most of the native rhizobia isolated from L. uliginosus were able to induce nodulation in all plant species studied. In a greenhouse experiment using both D. incanum and L. corniculatus plants, the rhizobia isolate UFRGS Lu2 promoted the greatest plant growth. The results demonstrate that there are native rhizobia in the soils of southern Brazil that have low host specificity and are able to induce nodulation and form active nodules in several plant species.

  8. Aging as an evolvability-increasing program which can be switched off by organism to mobilize additional resources for survival.

    Science.gov (United States)

    Skulachev, Maxim V; Severin, Fedor F; Skulachev, Vladimir P

    2015-01-01

    During the last decade, several pieces of convincing evidence were published indicating that aging of living organisms is programmed, being a particular case of programmed death of organism (phenoptosis). Among them, the following observations can be mentioned. (1) Species were described that show negligible aging. In mammals, the naked mole rat is the most impressive example. This is a rodent of mouse size living at least 10-fold longer than a mouse and having fecundity higher than a mouse and no agerelated diseases. (2) In some species with high aging rate, genes responsible for active organization of aging by poisoning of the organism with endogenous metabolites have been identified. (3) In women, standard deviations divided by the mean are the same for age of menarche (an event controlled by the ontogenetic program) and for age of menopause (an aging-related event). (4) Inhibitors of programmed cell death (apoptosis and necrosis) retard and in certain cases even reverse the development of age-dependent pathologies. (5) In aging species, the rate of aging is regulated by the individual which responds by changes in this rate to changes in the environmental conditions. In this review, we consider point (5) in detail. Data are summarized suggesting that inhibition of aging rate by moderate food restriction can be explained assuming that such restriction is perceived by the organism as a signal of future starvation. In response to this dramatic signal, the organism switches off such an optional program as aging, mobilizing in such a way additional reserves for survival. A similar explanation is postulated for geroprotective effects of heavy muscle work, a lowering or a rise in the external temperature, small amounts of metabolic poisons (hormesis), low doses of radiation, and other deleterious events. On the contrary, sometimes certain positive signals can prolong life by inhibiting the aging program in individuals who are useful for the community (e

  9. [Biomass allometric equations of nine common tree species in an evergreen broadleaved forest of subtropical China].

    Science.gov (United States)

    Zuo, Shu-di; Ren, Yin; Weng, Xian; Ding, Hong-feng; Luo, Yun-jian

    2015-02-01

    Biomass allometric equation (BAE) considered as a simple and reliable method in the estimation of forest biomass and carbon was used widely. In China, numerous studies focused on the BAEs for coniferous forest and pure broadleaved forest, and generalized BAEs were frequently used to estimate the biomass and carbon of mixed broadleaved forest, although they could induce large uncertainty in the estimates. In this study, we developed the species-specific and generalized BAEs using biomass measurement for 9 common broadleaved trees (Castanopsis fargesii, C. lamontii, C. tibetana, Lithocarpus glaber, Sloanea sinensis, Daphniphyllum oldhami, Alniphyllum fortunei, Manglietia yuyuanensis, and Engelhardtia fenzlii) of subtropical evergreen broadleaved forest, and compared differences in species-specific and generalized BAEs. The results showed that D (diameter at breast height) was a better independent variable in estimating the biomass of branch, leaf, root, aboveground section and total tree than a combined variable (D2 H) of D and H (tree height) , but D2H was better than D in estimating stem biomass. R2 (coefficient of determination) values of BAEs for 6 species decreased when adding H as the second independent variable into D- only BAEs, where R2 value for S. sinensis decreased by 5.6%. Compared with generalized D- and D2H-based BAEs, standard errors of estimate (SEE) of BAEs for 8 tree species decreased, and similar decreasing trend was observed for different components, where SEEs of the branch decreased by 13.0% and 20.3%. Therefore, the biomass carbon storage and its dynamic estimates were influenced largely by tree species and model types. In order to improve the accuracy of the estimates of biomass and carbon, we should consider the differences in tree species and model types.

  10. Is the male dog comparable to human? A histological study of the muscle systems of the lower urinary tract.

    Science.gov (United States)

    Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Do, Minh; Dorschner, Wolfgang; Salomon, Franz-Viktor; Jurina, Konrad; Neuhaus, Jochen

    2002-08-01

    Because of their superficial anatomical resemblance, the male dog seems to be suitable for studying the physiologic and pathological alterations of the bladder neck of human males. The present study was carried out to compare and contrast the muscular anatomy of the male dog lower urinary tract with that of humans. The complete lower urinary tract, including the surrounding organs (bulb of penis, prostate, rectum and musculature of the pelvic floor) were removed from adult and newborn male dogs and histologically processed using serial section technique. Based on our own histological investigations, three-dimensional (3D)-models of the anatomy of the lower urinary tract were constructed to depict the corresponding structures and the differences between the species. The results of this study confirm that the lower urinary tract of the male dog bears some anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and membranous urethra) to man. As with human males, the two parts of the musculus sphincter urethrae (glaber and transversostriatus) are evident in the canine bladder neck. Nevertheless, considerable differences in formation of individual muscles should be noted. In male dogs, no separate anatomic entity can be identified as vesical or internal sphincter. The individual course of the ventral and lateral longitudinal musculature and of the circularly arranged smooth musculature of the urethra is different to that of humans. Differences in the anatomy of individual muscles of the bladder neck in the male dog and man suggest that physiological interpretations of urethral functions obtained in one species cannot be attributed without qualification to the other.

  11. New World species of the genus Calliscelio Ashmead (Hymenoptera, Platygastridae, Scelioninae

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    Hua-yan Chen

    2017-01-01

    Full Text Available The genus Calliscelio Ashmead is presumed to be a diverse group of parasitoids of the eggs of crickets (Orthoptera: Gryllidae. A least one species has been found to be an important factor in depressing cricket pest populations. The New World species of Calliscelio are revised. Forty-two species are recognized, 3 are redescribed: C. bisulcatus (Kieffer, C. laticinctus Ashmead, C. rubriclavus (Ashmead, comb. n.; and 38 are described as new: C. absconditum Chen & Johnson, sp. n., C. absum Chen & Johnson, sp. n., C. alcoa Chen & Masner, sp. n., C. amadoi Chen & Johnson, sp. n., C. armila Chen & Masner, sp. n., C. bidens Chen & Masner, sp. n., C. brachys Chen & Johnson, sp. n., C. brevinotaulus Chen & Johnson, sp. n., C. brevitas Chen & Johnson, sp. n., C. carinigena Chen & Johnson, sp. n., C. crater Chen & Johnson, sp. n., C. crena Chen & Johnson, sp. n., C. eboris Chen & Johnson, sp. n., C. extenuatus Chen & Johnson, sp. n., C. flavicauda Chen & Johnson, sp. n., C. foveolatus Chen & Johnson, sp. n., C. gatineau Chen & Johnson, sp. n., C. glaber Chen & Masner, sp. n., C. granulatus Chen & Masner, sp. n., C. latifrons Chen & Johnson, sp. n., C. levis Chen & Johnson, sp. n., C. longius Chen & Johnson, sp. n., C. magnificus Chen & Masner, sp. n., C. migma Chen & Johnson, sp. n., C. minutia Chen & Johnson, sp. n., C. paraglaber Chen & Johnson, sp. n., C. pararemigio Chen & Masner, sp. n., C. prolixus Chen & Johnson, sp. n., C. punctatifrons Chen & Johnson, sp. n., C. remigio Chen & Masner, sp. n., C. ruga Chen & Johnson, sp. n., C. rugicoxa Chen & Masner, sp. n., C. sfina Chen & Johnson, sp. n., C. storea Chen & Johnson, sp. n., C. suni Chen & Johnson, sp. n., C. telum Chen & Johnson, sp. n., C. torqueo Chen & Johnson, sp. n., C. virga Chen & Johnson, sp. n. Four species are treated as junior synonyms of Calliscelio rubriclavus (Ashmead: Anteris nigriceps Ashmead, syn. n., Caloteleia marlattii Ashmead, syn. n., Caloteleia grenadensis Ashmead, syn. n

  12. Ouabaina como Hormona

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    J. Hernando Ordoñez

    1996-04-01

    Full Text Available

    Comentario sobre su origen endógeno y sus aplicaciones terapéuticas

    Pocas drogas han sido más estudiadas que el grupo de los digitálicos, estrofantinas y ouabaina, cuyo estudio es objeto del presente trabajo.

    La ouabaina empezó a ser estudiada desde el siglo pasado. La primera referencia conocida corresponde a Pelikan, 1865 (1, como veneno que empleaban para las flechas en Gabón (Africa. (.

    (. Vinieron luego los trabajos de Fraser, 1869, (2, 3, 6, Polaillon, 1871 (4, Amaud, 1888 (5, Vaquez y Lutembacher, 1917 (7, Stoll, 1939 (8, Lapicque, 1929 (9, Wiggers, 1927 (10, Ytantos otros (11, 12, 13. En la obra de Kisch (14 aparecen más de 700 referencias bibliográficas sobre el particular.

    Ouabaina de origen endógeno. Purificación
    Durante muchos años se conoció la ouabaina como de origen vegetal, elaborada por las plantas Strophanthus Glaber(k-estrofantina,AcocantheraOuabaio(Ouabaina yStrophanthus Kombe (k-estrofantina y kestrofantósido. Una propiedad común a todos los digitálicos, estrofantina y ouabaina es que todos son inhibidores de la bomba de Na-K, encargada de regular la salida de Na y la entrada de K celular.

    Estudiando los inhibido res de esta bomba han encontrado en años recientes resultados extraordinarios en relación con el origen endógeno de algunos de estos inhibidores, entre ellos la ouabaina. Por considerarlos de extrema importancia y actualidad científica me permito citar algunos de ellos. Hamlyn y Manunta (15, 16, 17, 18, Y 19 hicieron estudios sobre el particular y lograron identificar en el plasma humano un compuesto igual a la ouabaina. Estos hallazgos fueron confirmados después por otros autores (20, 21, 22, 23 Y24.

    Ham bl yn (19 da varios argumentos que ponen en evidencia que el compuesto químico encontrado es ouabaina pura, y, lo que es más interesante, que tiene un origen endógeno. a Por espectroscopia de alta resoluci