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Eviatar Nevo - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE Habitat and Burrow System Characteristics of the Blind Mole Rat Spalax galili in an Area of
    2016
    Co-Authors: Matěj Lovy, Jan Skliba, Eviatar Nevo, Ema Hrouzková, Veronika Dvořáková, Radim Šumbera
    Abstract:

    A costly search for food in subterranean rodents resulted in various adaptations improving their foraging success under given ecological conditions. In Spalax ehrenbergi superspe-cies, adaptations to local ecological conditions can promote speciation, which was recently supposed to occur even in sympatry at sites where two soil types of contrasting characteris-tics abut each other. Quantitative description of ecological conditions in such a site has been, nevertheless, missing. We measured characteristics of food supply and soil within 16 home ranges of Blind Mole rats Spalax galili in an area subdivided into two parts formed by basaltic soil and pale rendzina. We also mapped nine complete Mole rat burrow systems to compare burrowing patterns between the soil types. Basaltic soil had a higher food sup-ply and was harder than rendzina even under higher moisture content and lower bulk den-sity. Population density of Mole rats was five-times lower in rendzina, possibly due to the lower food supply and higher cover of Sarcopoterium shrubs which seem to be avoided by Mole rats. A combination of food supply and soil parameters probably influences burrowing patterns resulting in shorter and more complex burrow systems in basaltic soil

  • activity of free living subterranean Blind Mole rats spalax galili rodentia spalacidae in an area of supposed sympatric speciation
    Biological Journal of The Linnean Society, 2016
    Co-Authors: Jan Skliba, Matěj Lovy, Stephan C W Koeppen, Lucie Plestilova, Milos Vitamvas, Eviatar Nevo, Radim Šumbera
    Abstract:

    Subterranean rodents forage underground, which is energetically costly. Therefore, they can be expected to economize burrowing activity in response to food supply and soil characteristics. We analyzed the activity of radio-tracked Blind Mole rats, Spalax galili, on a locality sharply subdivided into harder but relatively food-rich, basaltic soil and softer, relatively food-poor rendzina. It was recently proposed that the Mole rats in this locality are undergoing sympatric ecological speciation. We predicted that Mole rats from basaltic soil would be less active than those from rendzina as a result of the reduced need for burrowing to reach food. By contrast to our predictions, Mole rats from basaltic soil were more frequently located outside the nest and observed pushing soil above ground. We suggest that this is a result of territorial behaviour due to high population density. All Mole rats exhibited a unimodal daily activity pattern likely related to temperature. Large males had large but gradually decreasing home-ranges, likely indicating the end of the mating season. We conclude that the ecological differences between the habitats cause behavioural differences in the Mole rats, which indicates different selection pressures. The genetic divergence previously found between the populations might have arisen via density-dependent selection.

  • Mechanisms regulating proteostasis are involved in sympatric speciation of the Blind Mole rat, Spalax galili
    Autophagy, 2016
    Co-Authors: Karl A. Rodriguez, Eviatar Nevo, Rochelle Buffenstein
    Abstract:

    Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between Blind Mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants.

  • correction corrigendum genome wide adaptive complexes to underground stresses in Blind Mole rats spalax
    Nature Communications, 2015
    Co-Authors: Xiaodong Fang, Aaron Avivi, Erez Y Levanon, Xuanting Jiang, Sergey Feranchuk, Alla Fishman, Eviatar Nevo, Denis M Larkin, Jing Zhao, Yue Feng
    Abstract:

    Nature Communications 5: Article number: 3966 (2014); Published online: 3 June 2014; Updated: 12 Aug 2015. In Fig. 2 of this Article, the CLOCK protein sequence of the Blind Mole rat (Spalax) was inadvertently used to represent that of the naked Mole rat (Heterocephalus glaber) in both the sequence alignment (Fig.

  • corrigendum genome wide adaptive complexes to underground stresses in Blind Mole rats spalax
    Nature Communications, 2015
    Co-Authors: Xiaodong Fang, Aaron Avivi, Erez Y Levanon, Xuanting Jiang, Sergey Feranchuk, Alla Fishman, Eviatar Nevo, Denis M Larkin, Jing Zhao, Yue Feng
    Abstract:

    Corrigendum: Genome-wide adaptive complexes to underground stresses in Blind Mole rats Spalax

Joseph Terkel - One of the best experts on this subject based on the ideXlab platform.

  • SEASONAL CHANGES IN THE OVARY OF THE Blind Mole RAT (SPALAX EHRENBERGI)
    Israel Journal of Zoology, 2013
    Co-Authors: Uri Shanas, Ruth Shalgi, Joseph Terkel
    Abstract:

    ABSTRACT The present study is the first to examine closely the ovary of the Blind Mole rat (Spalax ehrenbergi), a solitary, highly aggressive subterranean rodent. It provides basic data on the female reproductive biology which should assist in the notoriously difficult attempts to breed this unique species. Although the Mole rat is considered a seasonal breeder, large antral follicles were found to be present in the ovary throughout the year. Constant darkness and high temperatures simulating the natural burrow environment in the summer did not cause the ovary to regress. This was evident from the surprising abundance of large antral follicles, some even in the preovulatory state. Because injection of human chorionic gonadotropin (hCG) during the summer induces ovulation of these follicles, it would appear that Mole rats are potentially able to reproduce outside of the known winter breeding season. The present work further strengthens previous assumptions (based on vaginal smears) that the Mole rat is a r...

  • FIRST SUCCESSFUL BREEDING OF THE Blind Mole RAT (SPALAX EHRENBERGI) IN CAPTIVITY
    Israel Journal of Zoology, 2013
    Co-Authors: Irit Gazit, Uri Shanas, Joseph Terkel
    Abstract:

    ABSTRACT Breeding solitary fossorial mammals in captivity is notoriously difficult. To date, all attempts to breed the Blind Mole rat (Spalax ehrenbergi), a solitary and highly aggressive subterranean rodent, have failed. Consequently, its reproductive biology remains unknown. The present work is the first report of initiation of mating leading to successful pregnancy, delivery, and rearing of pups in captivity. Spalax ehrenbergi shows a 7–8 day periodicity in courtship behavior prior to the initiation of mounts. The length of pregnancy in this species is 34 days. A female and her son were housed for one year in a simulated burrow system where they established two independent adjacent territories. During the breeding season the animals had the option to avoid or initiate contact at will. This management concept of naturalistic conditions and minimal interference by the investigators undoubtedly contributed to the breeding success. The ability to breed this solitary aggressive fossorial rodent successfully...

  • Detours by the Blind Mole-rat follow assessment of location and physical properties of underground obstacles
    Animal Behaviour, 2003
    Co-Authors: Tali Kimchi, Joseph Terkel
    Abstract:

    Abstract Orientation by an animal inhabiting an underground environment must be extremely efficient if it is to contend effectively with the high energetic costs of excavating soil for a tunnel system. We examined, in the field, the ability of a fossorial rodent, the Blind Mole-rat, Spalax ehrenbergi, to detour different types of obstacles blocking its tunnel and rejoin the disconnected tunnel section. To create obstacles, we dug ditches, which we either left open or filled with stone or wood. Most (77%) Mole-rats reconnected the two parts of their tunnel and accurately returned to their orginal path by digging a parallel bypass tunnel around the obstacle at a distance of 10–20 cm from the open ditch boundaries or 3–8 cm from the filled ditch boundaries. When the ditch was placed asymmetrically across the tunnel, the Mole-rats detoured around the shorter side. These findings demonstrate that Mole-rats seem to be able to assess the nature of an obstacle ahead and their own distance from the obstacle boundaries, as well as the relative location of the far section of disconnected tunnel. We suggest that Mole-rats mainly use reverberating self-produced seismic vibrations as a mechanism to determine the size, nature and location of the obstacle, as well as internal self-generated references to determine their location relative to the disconnected tunnel section. Copyright 2003 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

  • Magnetic compass orientation in the Blind Mole rat Spalax ehrenbergi
    The Journal of Experimental Biology, 2001
    Co-Authors: Tali Kimchi, Joseph Terkel
    Abstract:

    The Blind Mole rat Spalax ehrenbergi is a solitary, subterranean rodent that digs and inhabits a system of branching tunnels, with no above-ground exits, which it never leaves unless forced to. To survive, the Mole rat must be able to orient efficiently in its tunnel system. The sensory channels available for spatial orientation in the subterranean environment are restricted in comparison with those existing above ground. This study examined the possibility that the Mole rat is able to perceive and use the earth9s magnetic field to orient in space. Experiments were performed using a device constructed from a pair of electromagnetic ‘Helmholtz coils’, which create a magnetic field whose direction and strength can be altered. In the first experiment, we tested a group of Mole rats (N=33) in an eight-armed maze under the earth9s natural magnetic field to determine whether they have directional preferences for the location of their sleeping nest, food chamber and toilet site. A second group of Mole rats (N=30) was tested for their directional preference after the earth9s magnetic field had been experimentally shifted by 180 degrees. We found that the first group exhibited a significant preference (P

  • STRUCTURE AND FUNCTION OF ACCESSORY SEX GLANDS IN THE MALE Blind Mole RAT (SPALAX EHRENBERGI)
    Journal of Mammalogy, 2001
    Co-Authors: A. Gottreich, Ilan Hammel, Leah Yogev, Benjamin Bartoov, Joseph Terkel
    Abstract:

    Abstract The Blind Mole rat (Spalax ehrenbergi) is a solitary and aggressive subterranean rodent. Our study revealed the unique anatomical structure of reproductive glands, ejaculate, and spermatozoon of the male Blind Mole rat and the effect of testosterone on those glands. Unlike other rodents, only the prostate and Cowper's accessory sex glands are present, whereas coagulating gland, seminal vesicle, and preputial gland are absent. Three groups of male Blind Mole rats were examined: intact, injected, and castrated animals, and resulting differences in morphology of reproductive glands were examined histologically using quantitative measurements. Lowered testosterone levels in castrated Blind Mole rats caused a reduction in weight and star volume (υ*) of the prostate and Cowper's glands. Testosterone injection produced an increase in mass of the prostate gland but not in Cowper's glands, whereas both prostate tubuli υ* and Cowper's gland tubuli υ* also increased. The Blind Mole rat possesses only 2 acce...

Imad Shams - One of the best experts on this subject based on the ideXlab platform.

  • The transcriptome landscape of the carcinogenic treatment response in the Blind Mole rat: insights into cancer resistance mechanisms
    BMC Genomics, 2019
    Co-Authors: Robert Altwasser, Aaron Avivi, Irena Manov, Abraham Korol, Imad Shams
    Abstract:

    Background Spalax , the Blind Mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax ’ cancer-resistance. Results We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway. Conclusion The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax . Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection.

  • The transcriptome landscape of the carcinogenic treatment response in the Blind Mole rat: insights into cancer resistance mechanisms.
    BMC genomics, 2019
    Co-Authors: Robert Altwasser, Aaron Avivi, Irena Manov, Abraham B. Korol, A. Paz, Imad Shams
    Abstract:

    Spalax, the Blind Mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax’ cancer-resistance. We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway. The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax. Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection.

  • adipose derived stem cells of Blind Mole rat spalax exhibit reduced homing ability Molecular mechanisms and potential role in cancer suppression
    Stem Cells, 2018
    Co-Authors: Anatolii Mamchur, Aaron Avivi, Imad Shams, Eva Leman, Safaa Salah, Irena Manov
    Abstract:

    Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant Blind Mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2'-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax's cancer resistance. Learning more about the Molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630-1642.

  • Adipose‐Derived Stem Cells of Blind Mole Rat Spalax Exhibit Reduced Homing Ability: Molecular Mechanisms and Potential Role in Cancer Suppression
    Stem cells (Dayton Ohio), 2018
    Co-Authors: Anatolii Mamchur, Aaron Avivi, Imad Shams, Eva Leman, Safaa Salah, Irena Manov
    Abstract:

    Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant Blind Mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2'-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax's cancer resistance. Learning more about the Molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630-1642.

  • Resistance to DNA damage and enhanced DNA repair capacity in the hypoxia-tolerant Blind Mole rat Spalax carmeli.
    The Journal of experimental biology, 2018
    Co-Authors: Vered Domankevich, Hossam Eddini, Amani Odeh, Imad Shams
    Abstract:

    Blind Mole rats of the genus Spalax are the only mammalian species to date for which spontaneous cancer has never been reported and resistance to carcinogen-induced cancers has been demonstrated. However, the underlying mechanisms are still poorly understood. The fact that Spalax spp. are also hypoxia-tolerant and long-lived species implies the presence of Molecular adaptations to prevent genomic instability, which underlies both cancer and aging. We previously demonstrated the upregulation of transcripts related to DNA replication and repair pathways in Spalax Yet, to date, no direct experimental evidence for improved genomic maintenance has been demonstrated for this genus. Here, we show that compared with skin fibroblasts of the above-ground rat, Spalax carmeli skin fibroblasts in culture resist several types of genotoxic insult, accumulate fewer genotoxic lesions and exhibit an enhanced DNA repair capacity. Our results strongly support that this species has evolved efficient mechanisms to maintain DNA integrity as an adaptation to the stressful conditions in the subterranean habitat.

Aaron Avivi - One of the best experts on this subject based on the ideXlab platform.

  • The transcriptome landscape of the carcinogenic treatment response in the Blind Mole rat: insights into cancer resistance mechanisms.
    BMC genomics, 2019
    Co-Authors: Robert Altwasser, Aaron Avivi, Irena Manov, Abraham B. Korol, A. Paz, Imad Shams
    Abstract:

    Spalax, the Blind Mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax’ cancer-resistance. We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway. The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax. Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection.

  • The transcriptome landscape of the carcinogenic treatment response in the Blind Mole rat: insights into cancer resistance mechanisms
    BMC Genomics, 2019
    Co-Authors: Robert Altwasser, Aaron Avivi, Irena Manov, Abraham Korol, Imad Shams
    Abstract:

    Background Spalax , the Blind Mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 years of Spalax research, no spontaneous cancer development has been observed. The mechanisms underlying this resistance are still not clarified. We investigated the genetic difference between Spalax and mice that might enable the Spalax relative resistance to cancer development. We compared Spalax and mice responses to a treatment with the carcinogen 3-Methylcholantrene, as a model to assess Spalax ’ cancer-resistance. Results We compared RNA-Seq data of untreated Spalax to Spalax with a tumor and identified a high number of differentially expressed genes. We filtered these genes by their expression in tolerant Spalax that resisted the 3MCA, and in mice, and found 25 genes with a consistent expression pattern in the samples susceptible to cancer among species. Contrasting the expressed genes in Spalax with benign granulomas to those in Spalax with malignant fibrosarcomas elucidated significant differences in several pathways, mainly related to the extracellular matrix and the immune system. We found a central cluster of ECM genes that differ greatly between conditions. Further analysis of these genes revealed potential microRNA targets. We also found higher levels of gene expression of some DNA repair pathways in Spalax than in other murines, like the majority of Fanconi Anemia pathway. Conclusion The comparison of the treated with the untreated tissue revealed a regulatory complex that might give an answer how Spalax is able to restrict the tumor growth. By remodeling the extracellular matrix, the possible growth is limited, and the proliferation of cancer cells was potentially prevented. We hypothesize that this regulatory cluster plays a major role in the cancer resistance of Spalax . Furthermore, we identified 25 additional candidate genes that showed a distinct expression pattern in untreated or tolerant Spalax compared to animals that developed a developed either a benign or malignant tumor. While further study is necessary, we believe that these genes may serve as candidate markers in cancer detection.

  • adipose derived stem cells of Blind Mole rat spalax exhibit reduced homing ability Molecular mechanisms and potential role in cancer suppression
    Stem Cells, 2018
    Co-Authors: Anatolii Mamchur, Aaron Avivi, Imad Shams, Eva Leman, Safaa Salah, Irena Manov
    Abstract:

    Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant Blind Mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2'-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax's cancer resistance. Learning more about the Molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630-1642.

  • Adipose‐Derived Stem Cells of Blind Mole Rat Spalax Exhibit Reduced Homing Ability: Molecular Mechanisms and Potential Role in Cancer Suppression
    Stem cells (Dayton Ohio), 2018
    Co-Authors: Anatolii Mamchur, Aaron Avivi, Imad Shams, Eva Leman, Safaa Salah, Irena Manov
    Abstract:

    Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant Blind Mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2'-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax's cancer resistance. Learning more about the Molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630-1642.

  • Genome maintenance and bioenergetics of the long-lived hypoxia-tolerant and cancer-resistant Blind Mole rat, Spalax: a cross-species analysis of brain transcriptome.
    Scientific reports, 2016
    Co-Authors: Assaf Malik, Aaron Avivi, Vered Domankevich, Abraham B. Korol, Han Lijuan, Fang Xiaodong, Imad Shams
    Abstract:

    The subterranean Blind Mole rat, Spalax, experiences acute hypoxia-reoxygenation cycles in its natural subterranean habitat. At the cellular level, these conditions are known to promote genomic instability, which underlies both cancer and aging. However, Spalax is a long-lived animal and is resistant to both spontaneous and induced cancers. To study this apparent paradox we utilized a computational procedure that allows detecting differences in transcript abundance between Spalax and the closely related above-ground Rattus norvegicus in individuals of different ages. Functional enrichment analysis showed that Spalax whole brain tissues maintain significantly higher normoxic mRNA levels of genes associated with DNA damage repair and DNA metabolism, yet keep significantly lower mRNA levels of genes involved in bioenergetics. Many of the genes that showed higher transcript abundance in Spalax are involved in DNA repair and metabolic pathways that, in other species, were shown to be downregulated under hypoxia, yet are required for overcoming replication- and oxidative-stress during the subsequent reoxygenation. We suggest that these differentially expressed genes may prevent the accumulation of DNA damage in mitotic and post-mitotic cells and defective resumption of replication in mitotic cells, thus maintaining genome integrity as an adaptation to acute hypoxia-reoxygenation cycles.

Shay Tzur - One of the best experts on this subject based on the ideXlab platform.

  • Adaptation of Pelage Color and Pigment Variations in Israeli Subterranean Blind Mole Rats, Spalax Ehrenbergi
    2016
    Co-Authors: Natarajan Singaravelan, Avigdor Beiles, Shirli Belifante, Shay Tzur, Tomáš Pavlíček, Shmuel Raz, Shosuke Ito
    Abstract:

    Background: 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. Methods: 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. Results: 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

  • adaptation of pelage color and pigment variations in israeli subterranean Blind Mole rats spalax ehrenbergi
    PLOS ONE, 2013
    Co-Authors: Natarajan Singaravelan, Avigdor Beiles, Shirli Belifante, Shay Tzur, Tomáš Pavlíček, Kazumasa Wakamatsu, Eviatar Nevo
    Abstract:

    The word "ehrenbergi," as part of a species name, was incorrectly capitalized in the title. The correct title is: Adaptation of Pelage Color and Pigment Variations in Israeli Subterranean Blind Mole Rats, Spalax ehrenbergi. The correct citation is: Singaravelan N, Raz S, Tzur S, Belifante S, Pavlicek T, et al. (2013) Adaptation of Pelage Color and Pigment Variations in Israeli Subterranean Blind Mole Rats, Spalax ehrenbergi. PLoS ONE 8(7): e69346. doi:10.1371/journal.pone.0069346.

  • possible incipient sympatric ecological speciation in Blind Mole rats spalax
    Proceedings of the National Academy of Sciences of the United States of America, 2013
    Co-Authors: Yarin Hadid, Avigdor Beiles, Radim Šumbera, Jan Skliba, Matěj Lovy, Shay Tzur, Tomáš Pavlíček, Ori Fragmansapir, Ran Arieli
    Abstract:

    Sympatric speciation has been controversial since it was first proposed as a mode of speciation. Subterranean Blind Mole rats (Spalacidae) are considered to speciate allopatrically or peripatrically. Here, we report a possible incipient sympatric adaptive ecological speciation in Spalax galili (2n = 52). The study microsite (0.04 km2) is sharply subdivided geologically, edaphically, and ecologically into abutting barrier-free ecologies divergent in rock, soil, and vegetation types. The Pleistocene Alma basalt abuts the Cretaceous Senonian Kerem Ben Zimra chalk. Only 28% of 112 plant species were shared between the soils. We examined mitochondrial DNA in the control region and ATP6 in 28 Mole rats from basalt and in 14 from chalk habitats. We also sequenced the complete mtDNA (16,423 bp) of four animals, two from each soil type. Remarkably, the frequency of all major haplotype clusters (HC) was highly soil-biased. HCI and HCII are chalk biased. HC-III was abundant in basalt (36%) but absent in chalk; HC-IV was prevalent in basalt (46.5%) but was low (20%) in chalk. Up to 40% of the mtDNA diversity was edaphically dependent, suggesting constrained gene flow. We identified a homologous recombinant mtDNA in the basalt/chalk studied area. Phenotypically significant divergences differentiate the two populations, inhabiting different soils, in adaptive oxygen consumption and in the amount of outside-nest activity. This identification of a possible incipient sympatric adaptive ecological speciation caused by natural selection indirectly refutes the allopatric alternative. Sympatric ecological speciation may be more prevalent in nature because of abundant and sharply abutting divergent ecologies.

  • Adaptation of Pelage Color and Pigment Variations in Israeli Subterranean Blind Mole Rats, Spalax Ehrenbergi
    2013
    Co-Authors: Natarajan Singaravelan, Avigdor Beiles, Shirli Belifante, Shay Tzur, Tomáš Pavlíček, Kazumasa Wakamatsu, Shmuel Raz, Shosuke Ito, Eviatar Nevo
    Abstract:

    BackgroundConcealing 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.MethodsWe 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.ResultsDue 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.Conclusion/SignificanceDarker 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 crypsis and thermoregulatory function following Gloger's rule.

  • odour genes covariance within a natural population of subterranean spalax galili Blind Mole rats
    Biological Journal of The Linnean Society, 2009
    Co-Authors: Shay Tzur, Eviatar Nevo, Josephine Todrank, Andreas Juergens, Giora Heth
    Abstract:

    Previous research, using habituation techniques with multiple rodent species as subjects, has demonstrated (from kin to across species) the greater perceptual similarity in the qualities of individual odours of more closely genetically related individuals (‘odour–genes covariance’, abbreviated ‘OGC’). This predictable relationship between individual genotypes and individual odours has only been assessed in rodents in which the genetic similarities and dissimilarities are known either through laboratory breeding or by selecting odour donors from different populations or species. To study OGC within a natural population of rodents, we genotyped Spalax galili Blind Mole rats using ten microsatellite markers, and conducted pairwise genetic distance comparisons to estimate genetic similarity and to calculate the relatedness coefficient between pairs of individuals. We then used habituation-generalization techniques to assess whether perceived odour similarities covaried with the genetic similarities we had identified. Indeed, animals treated odours from genetically closer donors as more similar than odours from less genetically similar donors. The results suggest an accurate and subtle ability to resolve genetically determined odour distinctions among familially unrelated animals within a population. Graded differential responses to conspecific odours based on degrees of similarity between other individuals' odours and one's own have been demonstrated in kinship and species discriminations and preferences. The evidence presented here provides the basis for hypothesizing a similar process that could promote optimal outbreeding and inclusive fitness within populations of conspecifics. The evolutionary implications of these findings are discussed. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 96, 483–490.