180 research outputs found
Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres
Full text linkUltrastructural Findings in the Murine Nonciliated Bronchiolar Cells (NCBC) after Subacute Inhalation of Lead Acetate
Full text linkLong-Term Socio-Ecological Research in the Biosphere Reserve in Mapimi, Mexico: A Multidimensional Participatory Observatory of Rangeland/Pastoral Systems
Get PDFSince the creation of the UNESCO Biosphere Reserve Mapimi (BRM) in Mexico 45 years ago, pastoralism has undergone a series of transformations. Upon the arrival of the Spaniards, horse breeding flourished until 1900; thereafter extensive cattle production lasted for six decades. Only recently, farmers have adopted alternative management types for organic meat production. National and international efforts to achieve the Sustainable Development Goals (SDGs) require basic, applied, and participatory research efforts. In the socio-ecological pastoral system BRM, first halophytic ecosystems were examined for their ecohydrological role in rangeland productivity. In 1996, a long-term ecological research site was installed to monitor the effects of herbivores on the composition and biodiversity of desert communities. Shortly thereafter, the National Commission of Natural Protected Areas began a rigorous monitoring and conservation program to guarantee both the sustainable management of natural resources and the sustainable development of reserve dwellers. Soon international multisectoral institutions joined Mexican efforts to protect the natural, cultural, and social diversity of the BRM and to strengthen its socio-ecological resilience to climate change and land degradation. Hence, the BRM is currently a space of participatory monitoring and research, with emphasis on the health of this important socio-ecological pastoralist system. It is examined whether institutional programs promoting organic livestock farming are compatible with this desert system and how biological soil crust is developing as a fundamental indicator of soil functioning and the provision of ecosystem services and human wellbeing. The formation of multisectoral partnerships to foster dryland sustainability have led to the foundation of the International Network for Dryland Sustainability; it is currently coordinating a national network of participatory socio-ecological observatories (PSEOs) to promote the SDGs. Mapimi is one of the first PSEOs to promote local governance and social and ecological sustainable development in the drylands of Mexico and world-wide
Participatory Observatories to Connect Multifunctional Landscapes, Link Smallholder Farmers, and Collectively Diversify Income
Get PDFCattle ranching was introduced to Baja California, Mexico (semiarid and arid climates) by the Spaniards, who brought the animals and the techniques. One important activity was moving livestock from the mountains (forests and few kinds of grass) to the coast crossing poor shrublands known as chaparrals. Fire was a common practice to promote grass growth and pastoralists could move through the land freely. Pastoralism became a common practice when English workers built the Ensenada port and became ranching landowners. They followed the practice of livestock movement through the exorreic watersheds. Native Indians, as well as other Mexicans known as ejidatarios, who had access to communal land, and wealthy livestock managers learned the same transhumance practices. They followed them until recently when privatizing the land began fragmenting the rangeland by installing fences; besides insecure places emerged due to illegal crop production. The Guadalupe watershed in Baja California is an interesting place to study rangelands as dynamic socio-ecological systems driven by institutional changes. Its land-use history has provoked interesting questions oriented to enlighten the future of livestock and rangeland management. This talk deals with the project of a citizen\u27s observatory where results from good local land and water management practices are being compiled and presented in a portal for its out-reach. The internet site will also make available scientific papers translated into infographics to make high-quality information accessible. Before and after special techniques like keyline design, holistic management, and other locally adapted techniques are being measured by ranchers and students as a citizen science program. We think that co-monitoring and improving data availability will facilitate local decision-making and deal with the multifunctionality of future rangelands in a better way
Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair
Get PDFKu70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70-/- cells and ku80 -/- cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase β (Pol β). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80-/- mice had a shorter life span than dna-pkcs-/- mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. © 2014 Choi et al
Effect of Ku80 Deficiency on Mutation Frequencies and Spectra at a LacZ Reporter Locus in Mouse Tissues and Cells
Get PDFNon-homologous end joining (NHEJ) is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs) and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and γH2AX DNA damage foci in Ku80−/− as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements
Current Bioengineering and Regenerative Strategies for the Generation of Kidney Grafts on Demand
Full text link[EN] Currently in the USA, one name is added to the organ transplant waiting list every 15 min. As this list grows rapidly, fewer than one-third of waiting patients can receive matched organs from donors. Unfortunately, many patients who require a transplant have to wait for long periods of time, and many of them die before receiving the desired organ. In the USA alone, over 100,000 patients are waiting for a kidney transplant. However, it is a problem that affects around 6% of the word population. Therefore, seeking alternative solutions to this problem is an urgent work. Here, we review the current promising regenerative technologies for kidney function replacement. Despite many approaches being applied in the different ways outlined in this work, obtaining an organ capable of performing complex functions such as osmoregulation, excretion or hormone synthesis is still a long-term goal. However, in the future, the efforts in these areas may eliminate the long waiting list for kidney transplants, providing a definitive solution for patients with end-stage renal disease.This study was supported by a grant from ALCER-TURIA, ASTELLAS and PRECIPITA CROWDFUNDING.Garcia-Dominguez, X.; Vicente Antón, JS.; Vera Donoso, CD.; Marco-Jiménez, F. (2017). Current Bioengineering and Regenerative Strategies for the Generation of Kidney Grafts on Demand. Current Urology Reports. 18(1):1-8. https://doi.org/10.1007/s11934-017-0650-6S18181Ott HC, Mathisen DJ. Bioartificial tissues and organs: are we ready to translate? Lancet. 2011;378:1977–8.Salvatori M, Peloso A, Katari R, Orlando G. Regeneration and bioengineering of the kidney: current status and future challenges. Curr Urol Rep. 2014;15:379.D’Agati VD. Growing new kidneys from embryonic cell suspensions: fantasy or reality? J Am Soc Nephrol. 2002;11:1763–6.Abouna GM. Organ shortage crisis: problems and possible solutions. Transplant Proc. 2008;40:34–8.Ozbolat IT, Yu Y. Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng. 2013;60:691–9.Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53.Meeus F, Kourilsky O, Guerin AP, Gaudry C, Marchais SJ, London GM. Pathophysiology of cardiovascular disease in hemodialysis patients. Kidney Int Suppl. 2000;76:140–7.Jofré R. Factores que afectan a la calidad de vida en pacientes en prediálisis, diálisis y trasplante renal. Nefrologia. 1999;19:84–90.Villa G, Rodríguez-Carmona A, Fernández-Ortiz L, Cuervo J, Rebollo P, Otero A, et al. Cost analysis of the Spanish renal replacement therapy programme. Nephrol Dial Transplant. 2011;26:3709–14.MJ C, Marshall D, Dilworth M, Bottomley M, Ashton N, Brenchley P. Immunosuppression is essential for successful allogeneic transplantation of the metanephroi. Transplantation. 2009;88:151–9.Xinaris C, Yokoo T. Reforming the kidney starting from a single-cell suspension. Nephron Exp Nephrol. 2014;126:107.Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin N Am. 2010;39:1–7.Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19:646–51.Hariharan K, Kurtz A, Schmidt-Ott KM. Assembling kidney tissues from cells: the long road from organoids to organs. Front Cell Dev Biol. 2015;3:70.Montserrat N, Garreta E, Izpisua Belmonte JC. Regenerative strategies for kidney engineering, FEBS J. 2016; in press. doi: 10.1111/febs.13704 .Hammerman MR. Transplantation of renal primordia: renal organogenesis. Pediatr Nephrol. 2007;22:1991–8.Basma H, Soto-Gutiérrez A, Yannam GR, Liu L, Ito R, Yamamoto T, et al. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology. 2009;136:990–9.Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27:275–80.Takahashi T, Lord B, Schulze PC, Fryer RM, Sarang SS, Gullans SR, et al. Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation. 2003;107:1912–6.Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res. 2009;19:429–38.Ledran MH, Krassowska A, Armstrong L, Dimmick I, Renström J, Lang R, et al. Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell. 2008;3:85–98.Yamanaka S, Yokoo T. Current bioengineering methods for whole kidney regeneration. Stem Cells Int. 2015;2015:724047.Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol. 2013;15:1507–15.Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, et al. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell. 2014;14:53–67.Simerman AA, Dumesic DA, Chazenbalk GD. Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy. Clin Transl Med. 2014;3:12.Verdi J, Tan A, Shoae-Hassani A, Seifalian AM. Endometrial stem cells in regenerative medicine. J Biol Eng. 2014;8:20.Maeshima A, Yamashita S, Nojima Y. Identification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney. J Am Soc Nephrol. 2003;14:3138–46.Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol. 2006;17:2443–56.Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest. 2004;114:795–804.Kitamura S, Yamasaki Y, Kinomura M, Sugaya T, Sugiyama H, Maeshima Y, et al. Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney. FASEB J. 2005;19:1789–97.Kitamura S, Sakurai H, Makino H. Single adult kidney stem/progenitor cells reconstitute three-dimensional nephron structures in vitro. Stem Cells. 2015;33:774–84.Li M, Suzuki K, Kim NY, Liu GH, Izpisua Belmonte JC. A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J Biol Chem. 2014;289:4594–9.Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015;6:8715.Hu J, Lei Y, Wong WK, Liu S, Lee KC, He X, et al. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. Nucleic Acids Res. 2014;42:4375–90.Den Hartogh SC, Schreurs C, Monshouwer-Kloots JJ, Davis RP, Elliott DA, Mummery CL, et al. Dual reporter MESP1 mCherry/w-NKX2-5 eGFP/w hESCs enable studying early human cardiac differentiation. Stem Cells. 2015;33:56–67.Fukui A, Yokoo T. Kidney regeneration using developing xenoembryo. Curr Opin Organ Transplant. 2015;20:160–4.Chen J, Lansford R, Stewart V, Young F, Alt FW. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc Natl Acad Sci U S A. 1993;90:4528–32.Ueno H, Turnbull BB, Weissman IL. Two-step oligoclonal development of male germ cells. Proc Natl Acad Sci U S A. 2009;106:175–80.Fraidenraich D, Stillwell E, Romero E, Wilkes D, Manova K, Basson CT, et al. Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science. 2004;306:247–52.Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata M, et al. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010;142:787–99.Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, et al. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proc Natl Acad Sci U S A. 2013;110:4557–62.Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, et al. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest. 2010;120:3120–6.Usui J, Kobayashi T, Yamaguchi T, Knisely AS, Nishinakamura R, Nakauchi H. Generation of kidney from pluripotent stem cells via blastocyst complementation. Am J Pathol. 2012;180:2417–26.Aggarwal S, Moggio A, Bussolati B. Concise review: stem/progenitor cells for renal tissue repair: current knowledge and perspectives. Stem Cells Transl Med. 2013;2:1011–9.Yokote S, Yokoo T. Organogenesis for kidney regeneration. Curr Opin Organ Transplant. 2013;18:186–90.Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32:3233–43.Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2011;2:403–30.Badylak SF. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol. 2004;12:367–77.Badylak SF. The extracellular matrix as a biologic scaffold material. Biomaterials. 2007;28:3587–93.Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.Yokoo T. Kidney regeneration with stem cells: an overview. Nephron Exp Nephrol. 2014;126(2):54.Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16:814–20.Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010;16:927–33.Montserrat N, Garreta E, Izpisua Belmonte JC. Regenerative strategies for kidney engineering. FEBS J. 2016. doi: 10.1111/febs.13704 .Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32:773–85.Groll J, Boland T, Blunk T, Burdick JA, Cho DW, Dalton PD, et al. Biofabrication: reappraising the definition of an evolving field. Biofabrication. 2016;8:013001.Mandrycky C, Wang Z, Kim K, Kim DH. 3D bioprinting for engineering complex tissues. Biotechnol Adv. 2016;34:422–34.Uzarski JS, Xia Y, Belmonte JC, Wertheim JA. New strategies in kidney regeneration and tissue engineering. Curr Opin Nephrol Hypertens. 2014;23:399–405.Humes HD, Buffington DA, MacKay SM, Funke AJ, Weitzel WF. Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol. 1999;17:451–5.Chevtchik NV, Fedecostante M, Jansen J, Mihajlovic M, Wilmer M, Rüth M, Masereeuw R, Stamatialis D. Upscaling of a living membrane for bioartificial kidney device. Eur J Pharmacol. 2016.Humes HD, Sobota JT, Ding F, Song JH. A selective cytopheretic inhibitory device to treat the immunological dysregulation of acute and chronic renal failure. Blood Purif. 2010;29:183–90.Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, et al. Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol. 2008;19:1034–40.Yokoo T, Ohashi T, Shen JS, Sakurai K, Miyazaki Y, Utsunomiya Y, et al. Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues. Proc Natl Acad Sci U S A. 2005;102(9):3296–300.Yokoo T, Fukui A, Ohashi T, Miyazaki Y, Utsunomiya Y, Kawamura T, et al. Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo. J Am Soc Nephrol. 2006;17:1026–34.Cooper DK. A brief history of cross-species organ transplantation. Proc (Bayl Univ Med Cent). 2012;25:49–57.Costa MR, Fischer N, Gulich B, Tönjes RR. Comparison of porcine endogenous retroviruses infectious potential in supernatants of producer cells and in cocultures. Xenotransplantation. 2014;21:162–73.Takeda S, Rogers SA, Hammerman MR. Differential origin for endothelial and mesangial cells after transplantation of pig fetal renal primordia into rats. Transpl Immunol. 2006;15:211–5.Yasutomi Y. Establishment of specific pathogen-free macaque colonies in Tsukuba Primate Research Center of Japan for AIDS research. Vaccine. 2010;28:75–7.Dekel B, Burakova T, Arditti FD, Reich-Zeliger S, Milstein O, Aviel-Ronen S, et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med. 2003;9:53–60.Hammerman MR. Classic and current opinion in embryonic organ transplantation. Curr Opin Organ Transplant. 2014;19:133–9.Rogers SA, Hammerman MR. Prolongation of life in anephric rats following de novo renal organogenesis. Organogenesis. 2004;1:22–5.•• Yokote S, Matsunari H, Iwai S, Yamanaka S, Uchikura A, Fujimoto E, et al. Urine excretion strategy for stem cell-generated embryonic kidneys. Proc Natl Acad Sci U S A. 2015;112:12980–5. This manuscript describes the developed-metanephros ability to produce urine when it was connected to the excretory system of the recipient organism. They demonstrated the potential of this technique as a possible solution to the kidneys shortage.Yokote S, Yokoo T, Matsumoto K, Utsunomiya Y, Kawamura T, Hosoya T. The effect of metanephroi transplantation on blood pressure in anephric rats with induced acute hypotension. Nephrol Dial Transplant. 2012;27:3449–55.Matsumoto K, Yokoo T, Yokote S, Utsunomiya Y, Ohashi T, Hosoya T. Functional development of a transplanted embryonic kidney: effect of transplantation site. J Nephrol. 2012;25:50–5.Yokote S, Yokoo T, Matsumoto K, Ohkido I, Utsunomiya Y, Kawamura T, et al. Metanephroi transplantation inhibits the progression of vascular calcification in rats with adenine-induced renal failure. Nephron Exp Nephrol. 2012;120:e32–40.Matsumoto K, Yokoo T, Matsunari H, Iwai S, Yokote S, Teratani T, et al. Xeno‐transplanted embryonic kidney provides a niche for endogenous mesenchymal stem cell differentiation into erythropoietin-producing tissue. Stem Cells. 2012;30:1228–35.Abrahamson DR. Glomerular development in intraocular and intrarenal graft of fetal kidney. Lab Investig. 1991;64:629–39.Woolf AS, Palmer SJ, Snow ML, Fine LG. Creation of functioning chimeric mammalian kidney. Kidney Int. 1990;38:991–7.Robert B, St John PL, Hyink DP, Abrahamson DR. Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts. Am J Physiol. 1996;271:F744–53.Koseki C, Herzlinger D, Al-Awqati Q. Integration of embryonic nephrogenic cells carrying a reporter gene into functioning nephrons. Am J Physiol. 1991;261:C550–4.Rogers SA, Lowell JA, Hammerman NA, Hammerman MR. Transplantation of developing metanephroi into adult rats. Kidney Int. 1998;54:27–37.Barakat TL, Harrison RG. The capacity of fetal and neonatal renal tissues to regenerate and differentiate in a heterotropic allogenic subcutaneous tissue site in the rat. J Anat. 1971;110:393–407.Rogers SA, Liapis H, Hammerman MR. Transplantation of metanephroi across the major histocompatibility complex in rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R132–6.Vera-Donoso CD, García-Dominguez X, Jiménez-Trigos E, García-Valero L, Vicente JS, Marco-Jiménez F. Laparoscopic transplantation of metanephroi: a first step to kidney xenotransplantation. Actas Urol Esp. 2015;39:527–34.•• Marco-Jiménez F, Garcia-Dominguez X, Jimenez-Trigos E, Vera-Donoso CD, Vicente JS. Vitrification of kidney precursors as a new source for organ transplantation. Cryobiology. 2015;70:278–82. This study found that it is possible to create a long-term biobank of kidney precursors as an unlimited source of organs for transplantation and open new therapeutic possibilities for the patients with chronic renal failure.Garcia-Dominguez X, Vicente JS, Vera-Donoso C, Jimenez-Trigos E, Marco-Jiménez F. First steps towards organ banks: vitrification of renal primordia. CryoLetters. 2016;37:47–52.•• García-Domínguez X, Vera-Donoso CD, García-Valero L, Vicente JS, Marco-Jiménez F. Embryonic organ transplantation: the new era of xenotransplantation. In: Abdeldayem H, El-Kased AF, El-Shaarawy A, editors. Frontiers in transplantology. 2016. pp. 26–46. This manuscript describes for the first time the protocol for transplantation of embryonic kidneys as an organ replacement therapy using laparoscopic surgery.Bottomley MJ, Baicu S, Boggs JM, Marshall DP, Clancy M, Brockbank KG, et al. Preservation of embryonic kidneys for transplantation. Transplant Proc. 2005;37:280–4.Hara J, Tottori J, Anders M, Dadhwal S, Asuri P, Mobed-Miremadi M. Trehalose effectiveness as a cryoprotectant in 2D and 3D cell cultures of human embryonic kidney cells. Artif Cells Nanomed Biotechnol. 2016. doi: 10.3109/21691401.2016.1167698 .Xu Y, Zhao G, Zhou X, Ding W, Shu Z, Gao D. Biotransport and intracellular ice formation phenomena in freezing human embryonic kidney cells (HEK293T). Cryobiology. 2014;68:294–302
The Candida albicans Ku70 Modulates Telomere Length and Structure by Regulating Both Telomerase and Recombination
Get PDFThe heterodimeric Ku complex has been shown to participate in DNA repair and telomere regulation in a variety of organisms. Here we report a detailed characterization of the function of Ku70 in the diploid fungal pathogen Candida albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type colony and cellular morphology, and are not sensitive to MMS or UV light. Interestingly, we observed complex effects of KU70 gene dosage on telomere lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres, and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of combination mutants suggests that the telomere elongation in the ku70 null mutant is due mostly to unregulated telomerase action. In addition, elevated levels of extrachromosomal telomeric circles were detected in the null mutant, consistent with activation of aberrant telomeric recombination. Altogether, our observations point to multiple mechanisms of the Ku complex in telomerase regulation and telomere protection in C. albicans, and reveal interesting similarities and differences in the mechanisms of the Ku complex in disparate systems
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