113 research outputs found

    Tractability in Constraint Satisfaction Problems: A Survey

    Get PDF
    International audienceEven though the Constraint Satisfaction Problem (CSP) is NP-complete, many tractable classes of CSP instances have been identified. After discussing different forms and uses of tractability, we describe some landmark tractable classes and survey recent theoretical results. Although we concentrate on the classical CSP, we also cover its important extensions to infinite domains and optimisation, as well as #CSP and QCSP

    Understanding single-station ground motion variability and uncertainty (sigma) – Lessons learnt from EUROSEISTEST

    Get PDF
    Accelerometric data from the well-studied valley EUROSEISTEST are used to investigate ground motion uncertainty and variability. We define a simple local ground motion prediction equation (GMPE) and investigate changes in standard deviation (σ) and its components, the between-event variability (τ) and within-event variability (φ). Improving seismological metadata significantly reduces τ (30-50%), which in turn reduces the total σ. Improving site information reduces the systematic site-to-site variability, φS2S (20-30%), in turn reducing φ, and ultimately, σ. Our values of standard deviations are lower than global values from literature, and closer to path-specific than site-specific values. However, our data have insufficient azimuthal coverage for single-path analysis. Certain stations have higher ground-motion variability, possibly due to topography, basin edge or downgoing wave effects. Sensitivity checks show that 3 recordings per event is a sufficient data selection criterion, however, one of the dataset’s advantages is the large number of recordings per station (9-90) that yields good site term estimates. We examine uncertainty components binning our data with magnitude from 0.01 to 2 s; at smaller magnitudes, τ decreases and φSS increases, possibly due to κ and source-site trade-offs Finally, we investigate the alternative approach of computing φSS using existing GMPEs instead of creating an ad hoc local GMPE. This is important where data are insufficient to create one, or when site-specific PSHA is performed. We show that global GMPEs may still capture φSS, provided that: 1. the magnitude scaling errors are accommodated by the event terms; 2. there are no distance scaling errors (use of a regionally applicable model). Site terms (φS2S) computed by different global GMPEs (using different site-proxies) vary significantly, especially for hard-rock sites. This indicates that GMPEs may be poorly constrained where they are sometimes most needed, i.e. for hard rock

    Explaining why simple liquids are quasi-universal

    Get PDF
    It has been known for a long time that many simple liquids have surprisingly similar structure as quantified, e.g., by the radial distribution function. A much more recent realization is that the dynamics are also very similar for a number of systems with quite different pair potentials. Systems with such non-trivial similarities are generally referred to as "quasi-universal". From the fact that the exponentially repulsive pair potential has strong virial potential-energy correlations in the low-temperature part of its thermodynamic phase diagram, we here show that a liquid is quasi-universal if its pair potential can be written approximately as a sum of exponential terms with numerically large prefactors. Based on evidence from the literature we moreover conjecture the converse, i.e., that quasi-universality only applies for systems with this property

    GATA2 Mediates Thyrotropin-Releasing Hormone-Induced Transcriptional Activation of the Thyrotropin β Gene

    Get PDF
    Thyrotropin-releasing hormone (TRH) activates not only the secretion of thyrotropin (TSH) but also the transcription of TSHβ and α-glycoprotein (αGSU) subunit genes. TSHβ expression is maintained by two transcription factors, Pit1 and GATA2, and is negatively regulated by thyroid hormone (T3). Our prior studies suggest that the main activator of the TSHβ gene is GATA2, not Pit1 or unliganded T3 receptor (TR). In previous studies on the mechanism of TRH-induced activation of the TSHβ gene, the involvements of Pit1 and TR have been investigated, but the role of GATA2 has not been clarified. Using kidney-derived CV1 cells and pituitary-derived GH3 and TαT1 cells, we demonstrate here that TRH signaling enhances GATA2-dependent activation of the TSHβ promoter and that TRH-induced activity is abolished by amino acid substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHβ gene. In CV1 cells transfected with TRH receptor expression plasmid, GATA2-dependent transactivation of αGSU and endothelin-1 promoters was enhanced by TRH. In the gel shift assay, TRH signal potentiated the DNA-binding capacity of GATA2. While inhibition by T3 is dominant over TRH-induced activation, unliganded TR or the putative negative T3-responsive element are not required for TRH-induced stimulation. Studies using GH3 cells showed that TRH-induced activity of the TSHβ promoter depends on protein kinase C but not the mitogen-activated protein kinase, suggesting that the signaling pathway is different from that in the prolactin gene. These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHβ expression

    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

    Gene Expression Programs of Mouse Endothelial Cells in Kidney Development and Disease

    Get PDF
    Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease

    The critical care management of poor-grade subarachnoid haemorrhage

    Full text link
    corecore