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Sample records for progenitor rencell vm

  1. Exploiting VM/XA

    International Nuclear Information System (INIS)

    Boeheim, C.

    1990-03-01

    The Stanford Linear Accelerator Center has recently completed a conversion to IBM's VM/XA SP Release 2 operating system. The primary physics application had been constrained by the previous 16 megabyte memory limit. Work is underway to enable this application to exploit the new features of VM/XA. This paper presents a brief tutorial on how to convert an application to exploit VM/XA and discusses some of the SLAC experiences in doing so. 13 figs

  2. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    Science.gov (United States)

    D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

    2015-01-01

    Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

  3. Delta-like 1 participates in the specification of ventral midbrain progenitor derived dopaminergic neurons

    DEFF Research Database (Denmark)

    Bauer, Matthias; Szulc, Jolanta; Meyer, Morten

    2008-01-01

    function of Dlk1 in VM neuron development, we investigated the effect of soluble Dlk1 protein as well as the intrinsic Dlk1 function in the course of VM progenitor expansion and dopaminergic (DA) neuron differentiation in vitro. Dlk1 treatment during expansion increased DA progenitor proliferation...

  4. CernVM Online and Cloud Gateway: a uniform interface for CernVM contextualization and deployment

    International Nuclear Information System (INIS)

    Lestaris, G; Charalampidis, I; Berzano, D; Blomer, J; Buncic, P; Ganis, G; Meusel, R

    2014-01-01

    In a virtualized environment, contextualization is the process of configuring a VM instance for the needs of various deployment use cases. Contextualization in CernVM can be done by passing a handwritten context to the user data field of cloud APIs, when running CernVM on the cloud, or by using CernVM web interface when running the VM locally. CernVM Online is a publicly accessible web interface that unifies these two procedures. A user is able to define, store and share CernVM contexts using CernVM Online and then apply them either in a cloud by using CernVM Cloud Gateway or on a local VM with the single-step pairing mechanism. CernVM Cloud Gateway is a distributed system that provides a single interface to use multiple and different clouds (by location or type, private or public). Cloud gateway has been so far integrated with OpenNebula, CloudStack and EC2 tools interfaces. A user, with access to a number of clouds, can run CernVM cloud agents that will communicate with these clouds using their interfaces, and then use one single interface to deploy and scale CernVM clusters. CernVM clusters are defined in CernVM Online and consist of a set of CernVM instances that are contextualized and can communicate with each other.

  5. Status and Roadmap of CernVM

    Science.gov (United States)

    Berzano, D.; Blomer, J.; Buncic, P.; Charalampidis, I.; Ganis, G.; Meusel, R.

    2015-12-01

    Cloud resources nowadays contribute an essential share of resources for computing in high-energy physics. Such resources can be either provided by private or public IaaS clouds (e.g. OpenStack, Amazon EC2, Google Compute Engine) or by volunteers computers (e.g. LHC@Home 2.0). In any case, experiments need to prepare a virtual machine image that provides the execution environment for the physics application at hand. The CernVM virtual machine since version 3 is a minimal and versatile virtual machine image capable of booting different operating systems. The virtual machine image is less than 20 megabyte in size. The actual operating system is delivered on demand by the CernVM File System. CernVM 3 has matured from a prototype to a production environment. It is used, for instance, to run LHC applications in the cloud, to tune event generators using a network of volunteer computers, and as a container for the historic Scientific Linux 5 and Scientific Linux 4 based software environments in the course of long-term data preservation efforts of the ALICE, CMS, and ALEPH experiments. We present experience and lessons learned from the use of CernVM at scale. We also provide an outlook on the upcoming developments. These developments include adding support for Scientific Linux 7, the use of container virtualization, such as provided by Docker, and the streamlining of virtual machine contextualization towards the cloud-init industry standard.

  6. Developing the Value Management Maturity Model (VM

    Directory of Open Access Journals (Sweden)

    Saipol Bari Abd Karim

    2013-06-01

    Full Text Available Value management (VM practices have been expanded and became a well-received technique globally. Organisations are now progressing towards a better implementation of VM and should be assessing their strengths and weaknesses in order to move forward competitively. There is a need to benchmark the existing VM practices to reflect their maturing levels which is currently not available. This paper outlines the concept of Value Management Maturity Model (VM3' as a structured plan of maturity and performance growth for businesses. It proposes five levels of maturity and each level has its own criteria or attributes to be achieved before progressing to a higher level. The framework for VM3' has been developed based on the review of literatures related to VM and maturity models (MM. Data is collected through questionnaire surveys to organisations that have implemented VM methodology. Additionally, semi-structured interviews were conducted to select individuals involved in implementing VM. The questions were developed to achieve the research objectives; investigating the current implementation of VM and, exploring the organisation's MM knowledge and practices. However, this research was limited to VM implementation in the Malaysian government's projects and programmes. VM3' introduces a new paradigm in VM as it provides a rating method for capabilities or performance. It is advocated that this VM3' framework is still being refined in the advance stage in order to provide a comprehensive and well accepted method to provide ratings for organisations' maturity.

  7. Security model for VM in cloud

    Science.gov (United States)

    Kanaparti, Venkataramana; Naveen K., R.; Rajani, S.; Padmvathamma, M.; Anitha, C.

    2013-03-01

    Cloud computing is a new approach emerged to meet ever-increasing demand for computing resources and to reduce operational costs and Capital Expenditure for IT services. As this new way of computation allows data and applications to be stored away from own corporate server, it brings more issues in security such as virtualization security, distributed computing, application security, identity management, access control and authentication. Even though Virtualization forms the basis for cloud computing it poses many threats in securing cloud. As most of Security threats lies at Virtualization layer in cloud we proposed this new Security Model for Virtual Machine in Cloud (SMVC) in which every process is authenticated by Trusted-Agent (TA) in Hypervisor as well as in VM. Our proposed model is designed to with-stand attacks by unauthorized process that pose threat to applications related to Data Mining, OLAP systems, Image processing which requires huge resources in cloud deployed on one or more VM's.

  8. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  9. Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

    Science.gov (United States)

    Rharass, Tareck; Lantow, Margareta; Gbankoto, Adam; Weiss, Dieter G; Panáková, Daniela; Lucas, Stéphanie

    2017-10-16

    Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA

  10. Moving to a total VM environment

    International Nuclear Information System (INIS)

    Johnston, T.Y.

    1981-01-01

    The Stanford Linear Accelerator Center is a single purpose laboratory operated by Stanford University for the Department of Energy. Its mission is to do research in High Energy (particle) physics. This research involves the use of large and complex electronic detectors. Each of these detectors is a multi-million dollar device. A part of each detector is a computer for process control and data logging. Most detectors at SLAC now use VAX 11/780s for this purpose. Most detectors record digital data via this process control computer. Consequently, physics today is not bounded by the cost of analog to digital conversion as it was in the past, and the physicist is able to run larger experiments than were feasible a decade ago. Today a medium sized experiment will produce several hundred full reels of 6250 BPI tape whereas a large experiment is a couple of thousand reels. The raw data must first be transformed into physics events using data transformation programs. The physicists then use subsets of the data to understand what went on. The subset may be anywhere from a few megabytes to 5 or 6 gigabytes of data (30 or 40 full reels of tape). This searching would be best solved interactively (if computers and I/0 devices were fast enough). Instead what we find are very dynamic batch programs that are generally changed every run. The result is that on any day there are probably around 50 to 100 physicists interacting with a half dozen different experiments who are causing us to mount around 750 to 1000 tapes a day. This has been the style of computing for the last decade. Our going to VM is part of our effort to change this style of computing and to make physics computing more effective

  11. Enabling μCernVM for the Interactive Use Case

    CERN Document Server

    Nicolaou, Vasilis

    2013-01-01

    The $\\mu$CernVM will be the successor of the CernVM as a new appliance to help with accessing LHC for data analysis and development. CernVM has a web appliance agent that facilitates user interaction with the virtual machine and reduces the need for executing shell commands or installing graphical applications for displaying basic information such as memory usage or performing simple tasks such as updating the operating system. The updates are done differently in the $\\mu$CernVM than mainstream Linux distributions. Its filesystem is a composition of a read-only layer that exists in the network and a read/write layer that is initilised on first boot and keeps the user changes afterwards. Thus, means are provided to avoid loss of user data and system instabilities when the operating system is updated by fetching a new read-only layer.

  12. CernVM - a virtual software appliance for LHC applications

    International Nuclear Information System (INIS)

    Buncic, P; Sanchez, C Aguado; Blomer, J; Franco, L; Mato, P; Harutyunian, A; Yao, Y

    2010-01-01

    CernVM is a Virtual Software Appliance capable of running physics applications from the LHC experiments at CERN. It aims to provide a complete and portable environment for developing and running LHC data analysis on any end-user computer (laptop, desktop) as well as on the Grid, independently of Operating System platforms (Linux, Windows, MacOS). The experiment application software and its specific dependencies are built independently from CernVM and delivered to the appliance just in time by means of a CernVM File System (CVMFS) specifically designed for efficient software distribution. The procedures for building, installing and validating software releases remains under the control and responsibility of each user community. We provide a mechanism to publish pre-built and configured experiment software releases to a central distribution point from where it finds its way to the running CernVM instances via the hierarchy of proxy servers or content delivery networks. In this paper, we present current state of CernVM project and compare performance of CVMFS to performance of traditional network file system like AFS and discuss possible scenarios that could further improve its performance and scalability.

  13. Porting of $\\mu$CernVM to AArch64

    CERN Document Server

    Scheffler, Felix

    2016-01-01

    $\\mu$CernVM is a virtual appliance that contains a stripped-down Linux OS connecting to a CernVM-Filesystem (CVMFS) repository that resides on a dedicated web server. In contrast to “usual” VMs, anything that is needed from this repository is only downloaded on demand, aggressively cached and eventually released again. Currently, $\\mu$CernVM is only distributed for x86-64. Recently, ARM (market leader in mobile computing) has started to enter the server market, which is still dominated by x86-64 infrastructure. However, in terms of performance/watt, AArch64 (latest ARM 64bit architecture) is a promising alternative. Facing millions of jobs to compute every day, it is thus desirable to have an HEP virtualisation solution for AArch64. In this project, $\\mu$CernVM was successfully ported to AArch64. Native and virtualised runtime performance was evaluated using ROOT6 and CMS benchmarks. It was found that VM performance is inferior to host performance across all tests. Respective numbers greatly vary between...

  14. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

    Science.gov (United States)

    Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

    2018-01-01

    Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  15. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

    Directory of Open Access Journals (Sweden)

    Yuki Fujiwara

    2018-02-01

    Full Text Available Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA, which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF, an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP, and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  16. Progenitor Epithelium

    Science.gov (United States)

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  17. Optimization of CernVM early boot process

    CERN Document Server

    Mazdin, Petra

    2015-01-01

    CernVM virtual machine is a Linux based virtual appliance optimized for High Energy Physics experiments. It is used for cloud computing, volunteer computing, and software development by the four large LHC experiments. The goal of this project is proling and optimizing the boot process of the CernVM. A key part was the development of a performance profiler for shell scripts as an extension to the popular BusyBox open source UNIX tool suite. Based on the measurements, costly shell code was replaced by more efficient, custom C programs. The results are compared to the original ones and successful optimization is proven.

  18. PEMILIHAN DAN MIGRASI VM MENGGUNAKAN MCDM UNTUK PENINGKATAN KINERJA LAYANAN PADA CLOUD COMPUTING

    Directory of Open Access Journals (Sweden)

    Abdullah Fadil

    2016-08-01

    Full Text Available Komputasi awan atau cloud computing merupakan lingkungan yang heterogen dan terdistribusi, tersusun atas gugusan jaringan server dengan berbagai kapasitas sumber daya komputasi yang berbeda-beda guna menopang model layanan yang ada di atasnya. Virtual machine (VM dijadikan sebagai representasi dari ketersediaan sumber daya komputasi dinamis yang dapat dialokasikan dan direalokasikan sesuai dengan permintaan. Mekanisme live migration VM di antara server fisik yang terdapat di dalam data center cloud digunakan untuk mencapai konsolidasi dan memaksimalkan utilisasi VM. Pada prosedur konsoidasi vm, pemilihan dan penempatan VM sering kali menggunakan kriteria tunggal dan statis. Dalam penelitian ini diusulkan pemilihan dan penempatan VM menggunakan multi-criteria decision making (MCDM pada prosedur konsolidasi VM dinamis di lingkungan cloud data center guna meningkatkan layanan cloud computing. Pendekatan praktis digunakan dalam mengembangkan lingkungan cloud computing berbasis OpenStack Cloud dengan mengintegrasikan VM selection dan VM Placement pada prosedur konsolidasi VM menggunakan OpenStack-Neat. Hasil penelitian menunjukkan bahwa metode pemilihan dan penempatan VM melalui live migration mampu menggantikan kerugian yang disebabkan oleh down-times sebesar 11,994 detik dari waktu responnya. Peningkatan response times terjadi sebesar 6 ms ketika terjadi proses live migration VM dari host asal ke host tujuan. Response times rata-rata setiap vm yang tersebar pada compute node setelah terjadi proses live migration sebesar 67 ms yang menunjukkan keseimbangan beban pada sistem cloud computing.

  19. SIMPLE HEURISTIC ALGORITHM FOR DYNAMIC VM REALLOCATION IN IAAS CLOUDS

    Directory of Open Access Journals (Sweden)

    Nikita A. Balashov

    2018-03-01

    Full Text Available The rapid development of cloud technologies and its high prevalence in both commercial and academic areas have stimulated active research in the domain of optimal cloud resource management. One of the most active research directions is dynamic virtual machine (VM placement optimization in clouds build on Infrastructure-as-a-Service model. This kind of research may pursue different goals with energy-aware optimization being the most common goal as it aims at a urgent problem of green cloud computing - reducing energy consumption by data centers. In this paper we present a new heuristic algorithm of dynamic reallocation of VMs based on an approach presented in one of our previous works. In the algorithm we apply a 2-rank strategy to classify VMs and servers corresponding to the highly and lowly active VMs and solve four tasks: VM classification, host classification, forming a VM migration map and VMs migration. Dividing all of the VMs and servers into two classes we attempt to implement the possibility of risk reduction in case of hardware overloads under overcommitment conditions and to reduce the influence of the occurring overloads on the performance of the cloud VMs. Presented algorithm was developed based on the workload profile of the JINR cloud (a scientific private cloud with the goal of maximizing its usage, but it can also be applied in both public and private commercial clouds to organize the simultaneous use of different SLA and QoS levels in the same cloud environment by giving each VM rank its own level of overcommitment.

  20. 3D-e-Chem-VM: Structural Cheminformatics Research Infrastructure in a Freely Available Virtual Machine

    NARCIS (Netherlands)

    McGuire, R.; Verhoeven, S.; Vass, M.; Vriend, G.; Esch, I.J. de; Lusher, S.J.; Leurs, R.; Ridder, L.; Kooistra, A.J.; Ritschel, T.; Graaf, C. de

    2017-01-01

    3D-e-Chem-VM is an open source, freely available Virtual Machine ( http://3d-e-chem.github.io/3D-e-Chem-VM/ ) that integrates cheminformatics and bioinformatics tools for the analysis of protein-ligand interaction data. 3D-e-Chem-VM consists of software libraries, and database and workflow tools

  1. 3D-e-Chem-VM : Structural Cheminformatics Research Infrastructure in a Freely Available Virtual Machine

    NARCIS (Netherlands)

    McGuire, Ross; Verhoeven, Stefan; Vass, Márton; Vriend, Gerrit; De Esch, Iwan J P; Lusher, Scott J.; Leurs, Rob; Ridder, Lars; Kooistra, Albert J.; Ritschel, Tina; de Graaf, C.

    2017-01-01

    3D-e-Chem-VM is an open source, freely available Virtual Machine ( http://3d-e-chem.github.io/3D-e-Chem-VM/ ) that integrates cheminformatics and bioinformatics tools for the analysis of protein-ligand interaction data. 3D-e-Chem-VM consists of software libraries, and database and workflow tools

  2. Micro-CernVM: slashing the cost of building and deploying virtual machines

    International Nuclear Information System (INIS)

    Blomer, J; Berzano, D; Buncic, P; Charalampidis, I; Ganis, G; Lestaris, G; Meusel, R; Nicolaou, V

    2014-01-01

    The traditional virtual machine (VM) building and and deployment process is centered around the virtual machine hard disk image. The packages comprising the VM operating system are carefully selected, hard disk images are built for a variety of different hypervisors, and images have to be distributed and decompressed in order to instantiate a virtual machine. Within the HEP community, the CernVM File System (CernVM-FS) has been established in order to decouple the distribution from the experiment software from the building and distribution of the VM hard disk images. We show how to get rid of such pre-built hard disk images altogether. Due to the high requirements on POSIX compliance imposed by HEP application software, CernVM-FS can also be used to host and boot a Linux operating system. This allows the use of a tiny bootable CD image that comprises only a Linux kernel while the rest of the operating system is provided on demand by CernVM-FS. This approach speeds up the initial instantiation time and reduces virtual machine image sizes by an order of magnitude. Furthermore, security updates can be distributed instantaneously through CernVM-FS. By leveraging the fact that CernVM-FS is a versioning file system, a historic analysis environment can be easily re-spawned by selecting the corresponding CernVM-FS file system snapshot.

  3. Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX.

    Science.gov (United States)

    Rice, Helen; Dalton, Christopher H; Price, Matthew E; Graham, Stuart J; Green, A Christopher; Jenner, John; Groombridge, Helen J; Timperley, Christopher M

    2015-04-08

    To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM-VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro . The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved.

  4. Experience on QA in the CernVM File System

    CERN Multimedia

    CERN. Geneva; MEUSEL, Rene

    2015-01-01

    The CernVM-File System (CVMFS) delivers experiment software installations to thousands of globally distributed nodes in the WLCG and beyond. In recent years it became a mission-critical component for offline data processing of the LHC experiments and many other collaborations. From a software engineering perspective, CVMFS is a medium-sized C++ system-level project. Following the growth of the project, we introduced a number of measures to improve the code quality, testability, and maintainability. In particular, we found very useful code reviews through github pull requests and automated unit- and integration testing. We are also transitioning to a test-driven development for new features and bug fixes. These processes are supported by a number of tools, such as Google Test, Jenkins, Docker, and others. We would like to share our experience on problems we encountered and on which processes and tools worked well for us.

  5. Investigating the role of the ventromedial prefrontal cortex (vmPFC in the assessment of brands

    Directory of Open Access Journals (Sweden)

    Jose Paulo eSantos

    2011-06-01

    Full Text Available The ventromedial prefrontal cortex (vmPFC is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI study where 18 subjects assessed positive, indifferent and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  6. Diffusion bonding of IN 718 to VM 350 grade maraging steel

    Science.gov (United States)

    Crosby, S. R.; Biederman, R. R.; Reynolds, C. C.

    1972-01-01

    Diffusion bonding studies have been conducted on IN 718, VM 350 and the dissimilar alloy couple, IN 718 to maraging steel. The experimental processing parameters critical to obtaining consistently good diffusion bonds between IN 718 and VM 350 were determined. Interrelationships between temperature, pressure and surface preparation were explored for short bending intervals under vacuum conditions. Successful joining was achieved for a range of bonding cycle temperatures, pressures and surface preparations. The strength of the weaker parent material was used as a criterion for a successful tensile test of the heat treated bond. Studies of VM-350/VM-350 couples in the as-bonded condition showed a greater yielding and failure outside the bond region.

  7. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  8. A VM-shared desktop virtualization system based on OpenStack

    Science.gov (United States)

    Liu, Xi; Zhu, Mingfa; Xiao, Limin; Jiang, Yuanjie

    2018-04-01

    With the increasing popularity of cloud computing, desktop virtualization is rising in recent years as a branch of virtualization technology. However, existing desktop virtualization systems are mostly designed as a one-to-one mode, which one VM can only be accessed by one user. Meanwhile, previous desktop virtualization systems perform weakly in terms of response time and cost saving. This paper proposes a novel VM-Shared desktop virtualization system based on OpenStack platform. The paper modified the connecting process and the display data transmission process of the remote display protocol SPICE to support VM-Shared function. On the other hand, we propose a server-push display mode to improve user interactive experience. The experimental results show that our system performs well in response time and achieves a low CPU consumption.

  9. Properties and Microstructure of Laser Welded VM12-SHC Steel Pipes Joints

    Directory of Open Access Journals (Sweden)

    Skrzypczyk A.

    2016-06-01

    Full Text Available Paper presents results of microstructure and tests of welded joints of new generation VM12-SHC martensitic steel using high power CO2 laser (LBW method with bifocal welding head. VM12-SHC is dedicated to energetic installation material, designed to replace currently used. High content of chromium and others alloying elements improve its resistance and strength characteristic. Use of VM12-SHC steel for production of the superheaters, heating chambers and walls in steam boilers resulted in various weldability researches. In article are presented results of destructive and non-destructive tests. For destructive: static bending and Vickers hardness tests, and for non-destructive: VT, RT, UT, micro and macroscopic tests were performed.

  10. Biological effects of 60Co γ-irradiation on Laiwu ginger VM1 growth

    International Nuclear Information System (INIS)

    Zhou Ming; Huang Jinli; Wei Yuxia; Guan Qiuzhu; Zhang Zhenxian

    2008-01-01

    Rhizome of Laiwu ginger were treated with γ-irradiation at the doses of 0, 20, 40 and 60 Gy. The results showed that 60 Co γ-irradiation inhibited the rhizome burgeoning, and decreased the survival rate of the seedlings, rate of leaf- expansion and the growth of plants (VM 1 ). The inhibition effects became stronger with the increase of the irradiation dose. Different bands were found through the analysis of POD, EST isozymes and RAPD of VM 1 plants, which showed that variation on molecular level occurred in VM 1 plants. LD 30-40 was appropriate for the irradiation of rhizomes of Laiwu ginger and the optimal irradiation dose was about 20- 30 Gy. (authors)

  11. Effects of topography on the functional development of human neural progenitor cells.

    Science.gov (United States)

    Wu, Ze-Zhi; Kisaalita, William S; Wang, Lina; Zachman, Angela L; Zhao, Yiping; Hasneen, Kowser; Machacek, Dave; Stice, Steven L

    2010-07-01

    We have fabricated a topographical substrate with a packed polystyrene bead array for the development of cell-based assay systems targeting voltage-gated calcium channels (VGCCs). Human neural progenitor cells (H945RB.3) cultured on both flat and topographical substrates were analyzed in terms of morphological spreading, neuronal commitment, resting membrane potential (V(m)) establishment and VGCC function development. We found, by SEM imaging, that arrayed substrates, formed with both sub-micrometer (of 0.51 microm in mean diameter) and micrometer (of 1.98 microm in mean diameter) beads, were capable of promoting the spreading of the progenitor cells as compared with the flat polystyrene surfaces. With the micrometer beads, it was found that arrayed substrates facilitated the neural progenitor cells' maintenance of less negative V(m) values upon differentiation with bFGF starvation, which favored predominant neuronal commitment. Almost all the progenitor cells were responsive to 50 mM K(+) depolarization with an increase in [Ca(2+)](i) either before or upon differentiation, suggesting the expression of functional VGCCs. Compared to the flat polystyrene surfaces, microbead arrayed substrates facilitated the development of higher VGCC responsiveness by the progenitor cells upon differentiation. The enhancement of both VGCC responsiveness and cell spreading by arrays of micrometer beads was most significant on day 14 into differentiation, which was the latest time point of measurement in this study. This study thus rationalized the possibility for future substrate topography engineering to manipulate ion channel function and to meet the challenge of low VGCC responsiveness found in early drug discovery.

  12. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

    Science.gov (United States)

    Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

    2010-07-23

    GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  13. Calorie Restriction as an Anti-Invasive Therapy for Malignant Brain Cancer in the VM Mouse

    Directory of Open Access Journals (Sweden)

    Laura M Shelton

    2010-07-01

    Full Text Available GBM (glioblastoma multiforme is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  14. HotpathVM: An Effective JIT for Resource-constrained Devices

    DEFF Research Database (Denmark)

    Gal, Andreas; Franz, Michael; Probst, Christian

    2006-01-01

    We present a just-in-time compiler for a Java VM that is small enough to fit on resource-constrained devices, yet surprisingly effective. Our system dynamically identifies traces of frequently executed bytecode instructions (which may span several basic blocks across several methods) and compiles...

  15. Overhead-Aware-Best-Fit (OABF) Resource Allocation Algorithm for Minimizing VM Launching Overhead

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hao [IIT; Garzoglio, Gabriele [Fermilab; Ren, Shangping [IIT, Chicago; Timm, Steven [Fermilab; Noh, Seo Young [KISTI, Daejeon

    2014-11-11

    FermiCloud is a private cloud developed in Fermi National Accelerator Laboratory to provide elastic and on-demand resources for different scientific research experiments. The design goal of the FermiCloud is to automatically allocate resources for different scientific applications so that the QoS required by these applications is met and the operational cost of the FermiCloud is minimized. Our earlier research shows that VM launching overhead has large variations. If such variations are not taken into consideration when making resource allocation decisions, it may lead to poor performance and resource waste. In this paper, we show how we may use an VM launching overhead reference model to minimize VM launching overhead. In particular, we first present a training algorithm that automatically tunes a given refer- ence model to accurately reflect FermiCloud environment. Based on the tuned reference model for virtual machine launching overhead, we develop an overhead-aware-best-fit resource allocation algorithm that decides where and when to allocate resources so that the average virtual machine launching overhead is minimized. The experimental results indicate that the developed overhead-aware-best-fit resource allocation algorithm can significantly improved the VM launching time when large number of VMs are simultaneously launched.

  16. 3D-e-Chem-VM: Structural Cheminformatics Research Infrastructure in a Freely Available Virtual Machine.

    Science.gov (United States)

    McGuire, Ross; Verhoeven, Stefan; Vass, Márton; Vriend, Gerrit; de Esch, Iwan J P; Lusher, Scott J; Leurs, Rob; Ridder, Lars; Kooistra, Albert J; Ritschel, Tina; de Graaf, Chris

    2017-02-27

    3D-e-Chem-VM is an open source, freely available Virtual Machine ( http://3d-e-chem.github.io/3D-e-Chem-VM/ ) that integrates cheminformatics and bioinformatics tools for the analysis of protein-ligand interaction data. 3D-e-Chem-VM consists of software libraries, and database and workflow tools that can analyze and combine small molecule and protein structural information in a graphical programming environment. New chemical and biological data analytics tools and workflows have been developed for the efficient exploitation of structural and pharmacological protein-ligand interaction data from proteomewide databases (e.g., ChEMBLdb and PDB), as well as customized information systems focused on, e.g., G protein-coupled receptors (GPCRdb) and protein kinases (KLIFS). The integrated structural cheminformatics research infrastructure compiled in the 3D-e-Chem-VM enables the design of new approaches in virtual ligand screening (Chemdb4VS), ligand-based metabolism prediction (SyGMa), and structure-based protein binding site comparison and bioisosteric replacement for ligand design (KRIPOdb).

  17. The Conserved Spore Coat Protein SpoVM Is Largely Dispensable in Clostridium difficile Spore Formation.

    Science.gov (United States)

    Ribis, John W; Ravichandran, Priyanka; Putnam, Emily E; Pishdadian, Keyan; Shen, Aimee

    2017-01-01

    The spore-forming bacterial pathogen Clostridium difficile is a leading cause of health care-associated infections in the United States. In order for this obligate anaerobe to transmit infection, it must form metabolically dormant spores prior to exiting the host. A key step during this process is the assembly of a protective, multilayered proteinaceous coat around the spore. Coat assembly depends on coat morphogenetic proteins recruiting distinct subsets of coat proteins to the developing spore. While 10 coat morphogenetic proteins have been identified in Bacillus subtilis , only two of these morphogenetic proteins have homologs in the Clostridia : SpoIVA and SpoVM. C. difficile SpoIVA is critical for proper coat assembly and functional spore formation, but the requirement for SpoVM during this process was unknown. Here, we show that SpoVM is largely dispensable for C. difficile spore formation, in contrast with B. subtilis . Loss of C. difficile SpoVM resulted in modest decreases (~3-fold) in heat- and chloroform-resistant spore formation, while morphological defects such as coat detachment from the forespore and abnormal cortex thickness were observed in ~30% of spoVM mutant cells. Biochemical analyses revealed that C. difficile SpoIVA and SpoVM directly interact, similarly to their B. subtilis counterparts. However, in contrast with B. subtilis , C. difficile SpoVM was not essential for SpoIVA to encase the forespore. Since C. difficile coat morphogenesis requires SpoIVA-interacting protein L (SipL), which is conserved exclusively in the Clostridia , but not the more broadly conserved SpoVM, our results reveal another key difference between C. difficile and B. subtilis spore assembly pathways. IMPORTANCE The spore-forming obligate anaerobe Clostridium difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. When C. difficile spores are ingested by susceptible individuals, they germinate within the gut and

  18. Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC.

    Science.gov (United States)

    Miller, Bailey W; Wroten, Melissa G; Sacramento, Arianne D; Silva, Hannah E; Shin, Christina B; Vieira, Philip A; Ben-Shahar, Osnat; Kippin, Tod E; Szumlinski, Karen K

    2017-05-01

    In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular signal-regulated kinase observed in cocaine-seeking rats. Further, the impact of inhibiting PKCε translocation within the vmPFC using TAT infusion proteins upon cue-elicited responding was determined and inhibition coinciding with the period of testing attenuated cocaine-seeking behavior, with an effect also apparent the next day. In contrast, inhibitor pretreatment prior to testing during early withdrawal was without effect. Thus, a history of excessive cocaine taking influences the cue reactivity of important intracellular signaling molecules within the vmPFC, with PKCε playing a critical role in the manifestation of cue-elicited cocaine seeking during protracted drug withdrawal. © 2016 Society for the Study of Addiction.

  19. Progenitors of white dwarfs

    International Nuclear Information System (INIS)

    Drilling, J.S.; Schoenberner, D.

    1985-01-01

    Direct observational evidence is presented which indicates that the immediate progenitors of white dwarfs are the central stars of planetary nebulae (approximately 70%), other post-AGB objects (approximately 30%), and post-HB objects not massive enough to climb the AGB (approximately 0.3%). The combined birth rate for these objects is in satisfactory agreement with the death rate of main-sequence stars and the birth rate of white dwarfs

  20. Masses of supernova progenitors

    International Nuclear Information System (INIS)

    Tinsley, B.M.

    1977-01-01

    The possible nature and masses of supernovae progenitors, and the bearing of empirical results on some unsolved theoretical problems concerning the origin of supernovae, are discussed. The author concentrates on two main questions: what is the lower mass limit for stars to die explosively and what stars initiate type I supernovae. The evidence considered includes local supernova rates, empirical estimates of msub(w) (the upper mass limit for death as a white dwarf), the distributions of supernovae among stellar populations in galaxies and the colors of supernova producing galaxies. (B.D.)

  1. Studying VM-1 molybdenum alloy workability at high current density. II

    Energy Technology Data Exchange (ETDEWEB)

    Tatarinova, O M; Amirkhanova, N A; Zaripov, R A

    1976-01-01

    Under galvanostatic conditions, voltampere characteristics have been taken off for VM-1 alloy; determined are also the selective effect of electrolytes and the influence of hydrodynamical conditions on the rate of anodic dissolution in the electrolytes containing 15% NaNO/sub 3/; 15% NaNO/sub 3/ + 5% NaOH, and 15 % NaOH. In a composite electrolyte, the quality of the surface is improved, and higher current densities have been attained as compared with those for pure 15% NaNO/sub 3/. The process of dissolution in the above electrolytes is effected with diffuse limitations. For the electrochemical treatment of the VM-1 alloy under production conditions, a composite electrolyte containing 15% NaNO/sub 3/ and 5% NaOH has been suggested and tested.

  2. Investigation into electrochemical behavior of molybdenum VM-1 alloy at high current density

    Energy Technology Data Exchange (ETDEWEB)

    Tatarinova, O M; Amirkhanova, N A; Akhmadiev, A G

    1975-01-01

    The effect of the composition and concentration of electrolyte on the workability of the molybdenum VM-1 alloy has been studied and a number of anions has been determined relative to their activation capacity. The best workability of the alloy is achieved in a 15% NaOH solution and a composite electrolyte 15% NaNO/sub 3/+5%NaOH. It is shown that in polarization of the VM-1 alloy both in alkali- and salt solutions a film of oxides of different valence molybdenum is formed: Mo/sub 2/O/sub 3/, Mo/sub 4/O/sub 11/, Mo/sub 9/O/sub 26/, MoO/sub 3/, but molybdenum gets dissolved only in a hexavalent form, its content in a solution being in conformity with the polarizing current densities. Using a temperature-kinetic technique it has been found that the concentrational polarization is the limiting stage in the reaction of molybdenum and VM-1 alloy anodic dissolution in 15% NaNO/sub 3/ solution and in the composite electrolyte 15%NaNO/sub 3/+5%NaOH.

  3. cernatschool.org's use of CVMFS and the CernVM

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    cernatschool.org is a very small Virtual Organisation made up of secondary school and university students, and participating organisations in the Institute for Research in Schools. We use CVMFS to delpoy dependencies and Python 3 itself for custom software used for analysing radiation data from Medipix detectors. This software is designed for running on GridPP worker nodes, part of the UK based distributed computing grid. The cernatschool.org VO also uses the CernVM, for job submission and interacting with the grid. The current use for both CVMFS and the CernVM is for facilitating analysis of 3 years worth of data from the LUCID payload on TechDemoSat-1. The CernVM looks like it could be particularly useful in the future for a standard system for students to use to program and analyse data themselves with, allowing easy access to any software they might need (not necessarily using GridPP compute resources at all).

  4. Physical metallurgy: Scientific school of the Academician V.M. Schastlivtsev

    Science.gov (United States)

    Tabatchikova, T. I.

    2016-04-01

    This paper is to honor Academician Vadim Mikhailovich Schastlivtsev, a prominent scientist in the field of metal physics and materials science. The article comprises an analysis of the topical issues of the physical metallurgy of the early 21st century and of the contribution of V.M. Schastlivtsev and of his school to the science of phase and structural transformations in steels. In 2015, Vadim Mikhailovich celebrates his 80th birthday, and this paper is timed to this honorable date. The list of his main publications is given in it.

  5. Dynamic virtual AliEn Grid sites on Nimbus with CernVM

    International Nuclear Information System (INIS)

    Harutyunyan, A; Buncic, P; Freeman, T; Keahey, K

    2010-01-01

    We describe the work on enabling one click deployment of Grid sites of AliEn Grid framework on the Nimbus 'science cloud' at the University of Chicago. The integration of computing resources of the cloud with the resource pool of AliEn Grid is achieved by leveraging two mechanisms: the Nimbus Context Broker developed at Argonne National Laboratory and the University of Chicago, and CernVM - a baseline virtual software appliance for LHC experiments developed at CERN. Two approaches of dynamic virtual AliEn Grid site deployment are presented.

  6. Development of a Temperature Controller for a Vuilleumier (VM) Cycle Power Cylinder

    Science.gov (United States)

    1975-10-01

    the system in the event of a shorted sensor; both of these actions turn the power section of the controller "off," and it cannot be repowered until...400-Hz power to a low-level DC with the attendant necessity of using a 400-Hz power transformer . Thus use of DC will allow a less compli- cated...N AFFDL.TR-75-99 7? ^0 00 o o o CQ DEVELOPMENT OF A TEMPERATURE CONTROLLER FOR A VUILLEUMIER (VM) CYCLE POWER CYLINDER i ■ L RTHUR D

  7. Security in the CernVM File System and the Frontier Distributed Database Caching System

    International Nuclear Information System (INIS)

    Dykstra, D; Blomer, J

    2014-01-01

    Both the CernVM File System (CVMFS) and the Frontier Distributed Database Caching System (Frontier) distribute centrally updated data worldwide for LHC experiments using http proxy caches. Neither system provides privacy or access control on reading the data, but both control access to updates of the data and can guarantee the authenticity and integrity of the data transferred to clients over the internet. CVMFS has since its early days required digital signatures and secure hashes on all distributed data, and recently Frontier has added X.509-based authenticity and integrity checking. In this paper we detail and compare the security models of CVMFS and Frontier.

  8. Security in the CernVM File System and the Frontier Distributed Database Caching System

    Science.gov (United States)

    Dykstra, D.; Blomer, J.

    2014-06-01

    Both the CernVM File System (CVMFS) and the Frontier Distributed Database Caching System (Frontier) distribute centrally updated data worldwide for LHC experiments using http proxy caches. Neither system provides privacy or access control on reading the data, but both control access to updates of the data and can guarantee the authenticity and integrity of the data transferred to clients over the internet. CVMFS has since its early days required digital signatures and secure hashes on all distributed data, and recently Frontier has added X.509-based authenticity and integrity checking. In this paper we detail and compare the security models of CVMFS and Frontier.

  9. Using XRootD to provide caches for CernVM-FS

    CERN Document Server

    Domenighini, Matteo

    2017-01-01

    CernVM-FS recently added the possibility of using plugin for cache management. In order to investigate the capabilities and limits of such possibility, an XRootD plugin was written and benchmarked; as a byproduct, a POSIX plugin was also generated. The tests revealed that the plugin interface introduces no signicant performance over- head; moreover, the XRootD plugin performance was discovered to be worse than the ones of the built-in cache manager and the POSIX plugin. Further test of the XRootD component revealed that its per- formance is dependent on the server disk speed.

  10. Managing the Virtual Machine Lifecycle of the CernVM Project

    International Nuclear Information System (INIS)

    Charalampidis, I; Blomer, J; Buncic, P; Harutyunyan, A; Larsen, D

    2012-01-01

    CernVM is a virtual software appliance designed to support the development cycle and provide a runtime environment for LHC applications. It consists of a minimal Linux distribution, a specially tuned file system designed to deliver application software on demand, and contextualization tools. The maintenance of these components involves a variety of different procedures and tools that cannot always connect with each other. Additionally, most of these procedures need to be performed frequently. Currently, in the CernVM project, every time we build a new virtual machine image, we have to perform the whole process manually, because of the heterogeneity of the tools involved. The overall process is error-prone and time-consuming. Therefore, to simplify and aid this continuous maintenance process, we are developing a framework that combines these virtually unrelated tools with a single, coherent interface. To do so, we identified all the involved procedures and their tools, tracked their dependencies and organized them into logical groups (e.g. build, test, instantiate). These groups define the procedures that are performed throughout the lifetime of a virtual machine. In this paper we describe the Virtual Machine Lifecycle and the framework we developed (iAgent) in order to simplify the maintenance process.

  11. VMCast: A VM-Assisted Stability Enhancing Solution for Tree-Based Overlay Multicast.

    Directory of Open Access Journals (Sweden)

    Weidong Gu

    Full Text Available Tree-based overlay multicast is an effective group communication method for media streaming applications. However, a group member's departure causes all of its descendants to be disconnected from the multicast tree for some time, which results in poor performance. The above problem is difficult to be addressed because overlay multicast tree is intrinsically instable. In this paper, we proposed a novel stability enhancing solution, VMCast, for tree-based overlay multicast. This solution uses two types of on-demand cloud virtual machines (VMs, i.e., multicast VMs (MVMs and compensation VMs (CVMs. MVMs are used to disseminate the multicast data, whereas CVMs are used to offer streaming compensation. The used VMs in the same cloud datacenter constitute a VM cluster. Each VM cluster is responsible for a service domain (VMSD, and each group member belongs to a specific VMSD. The data source delivers the multicast data to MVMs through a reliable path, and MVMs further disseminate the data to group members along domain overlay multicast trees. The above approach structurally improves the stability of the overlay multicast tree. We further utilized CVM-based streaming compensation to enhance the stability of the data distribution in the VMSDs. VMCast can be used as an extension to existing tree-based overlay multicast solutions, to provide better services for media streaming applications. We applied VMCast to two application instances (i.e., HMTP and HCcast. The results show that it can obviously enhance the stability of the data distribution.

  12. vmPFC activation during a stressor predicts positive emotions during stress recovery

    Science.gov (United States)

    Yang, Xi; Garcia, Katelyn M; Jung, Youngkyoo; Whitlow, Christopher T; McRae, Kateri; Waugh, Christian E

    2018-01-01

    Abstract Despite accruing evidence showing that positive emotions facilitate stress recovery, the neural basis for this effect remains unclear. To identify the underlying mechanism, we compared stress recovery for people reflecting on a stressor while in a positive emotional context with that for people in a neutral context. While blood–oxygen-level dependent data were being collected, participants (N = 43) performed a stressful anagram task, which was followed by a recovery period during which they reflected on the stressor while watching a positive or neutral video. Participants also reported positive and negative emotions throughout the task as well as retrospective thoughts about the task. Although there was no effect of experimental context on emotional recovery, we found that ventromedial prefrontal cortex (vmPFC) activation during the stressor predicted more positive emotions during recovery, which in turn predicted less negative emotions during recovery. In addition, the relationship between vmPFC activation and positive emotions during recovery was mediated by decentering—the meta-cognitive detachment of oneself from one’s feelings. In sum, successful recovery from a stressor seems to be due to activation of positive emotion-related regions during the stressor itself as well as to their downstream effects on certain cognitive forms of emotion regulation. PMID:29462404

  13. CernVM Co-Pilot: an Extensible Framework for Building Scalable Cloud Computing Infrastructures

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    CernVM Co-Pilot is a framework for instantiating an ad-hoc computing infrastructure on top of distributed computing resources. Such resources include commercial computing clouds (e.g. Amazon EC2), scientific computing clouds (e.g. CERN lxcloud), as well as the machines of users participating in volunteer computing projects (e.g. BOINC). The framework consists of components that communicate using the Extensible Messaging and Presence protocol (XMPP), allowing for new components to be developed in virtually any programming language and interfaced to existing Grid and batch computing infrastructures exploited by the High Energy Physics community. Co-Pilot has been used to execute jobs for both the ALICE and ATLAS experiments at CERN. CernVM Co-Pilot is also one of the enabling technologies behind the LHC@home 2.0 volunteer computing project, which is the first such project that exploits virtual machine technology. The use of virtual machines eliminates the necessity of modifying existing applications and adapt...

  14. Universal Voltage Conveyor and its Novel Dual-Output Fully-Cascadable VM APF Application

    Directory of Open Access Journals (Sweden)

    Norbert Herencsar

    2017-03-01

    Full Text Available This letter presents a novel realization of a voltage-mode (VM first-order all-pass filter (APF with attractive features. The proposed circuit employs a single readily available six-terminal active device called as universal voltage conveyor (UVC and only grounded passive components, which predict its easy monolithic integration with desired circuit simplicity. The auxiliary voltage input (W and output (ZP, ZN terminals of the device fully ensure easy cascadability of VM APF, since the input and output terminal impedances are theoretically infinitely high and zero, respectively. Moreover, thanks to mutually inverse outputs of the UVC, the proposed filter simultaneously provides both inverting and non-inverting outputs from the same configuration. All of these features make the UVC a unique active device currently available in the literature. The behavior of the filter was experimentally measured using the readily available UVC-N1C 0520 chip, which was produced in cooperation with ON Semiconductor Czech Republic, Ltd.

  15. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  16. On Use of the Variable Zagreb vM2 Index in QSPR: Boiling Points of Benzenoid Hydrocarbons

    Directory of Open Access Journals (Sweden)

    Albin Jurić

    2004-12-01

    Full Text Available The variable Zagreb vM2 index is introduced and applied to the structure-boiling point modeling of benzenoid hydrocarbons. The linear model obtained (thestandard error of estimate for the fit model Sfit=6.8 oC is much better than thecorresponding model based on the original Zagreb M2 index (Sfit=16.4 oC. Surprisingly,the model based on the variable vertex-connectivity index (Sfit=6.8 oC is comparable tothe model based on vM2 index. A comparative study with models based on the vertex-connectivity index, edge-connectivity index and several distance indices favours modelsbased on the variable Zagreb vM2 index and variable vertex-connectivity index.However, the multivariate regression with two-, three- and four-descriptors givesimproved models, the best being the model with four-descriptors (but vM2 index is notamong them with Sfit=5 oC, though the four-descriptor model contaning vM2 index isonly slightly inferior (Sfit=5.3 oC.

  17. Research and Implementation of Software Used for the Remote Control for VM700T Video Measuring Instrument

    Directory of Open Access Journals (Sweden)

    Song Wenjie

    2015-01-01

    Full Text Available In this paper, the measurement software which can be used to realize remote control of the VM700T video measuring instrument is introduced. The authors can operate VM700T by a virtual panel on the client computer, select the results that the measuring equipment displayed to transmit it, and then display the image on the VM700T virtual panel in real time. The system does have some practical values and play an important role in distance learning. The functions that the system realized mainly includes four aspects: the real-time transmission of message based on the socket technology, the serial connection between server PC and VM700T measuring equipment, the image acquisition based on VFW technology and JPEG compression and decompression, and the network transmission of image files. The actual network transmission test is shown that the data acquisition method of this thesis is flexible and convenient, and the system is of extraordinary stability. It can display the measurement results in real time and basically realize the requirements of remote control. In the content, this paper includes a summary of principle, the detailed introduction of the system realization process and some related technology.

  18. The effect of future time perspective on delay discounting is mediated by the gray matter volume of vmPFC.

    Science.gov (United States)

    Guo, Yiqun; Chen, Zhiyi; Feng, Tingyong

    2017-07-28

    Although several previous studies have shown that individuals' attitude towards time could affect their intertemporal preference, little is known about the neural basis of the relation between time perspective (TP) and delay discounting. In the present study, we quantified the gray matter (GM) cortical volume using voxel-based morphometry (VBM) methods to investigate the effect of TP on delay discounting (DD) across two independent samples. For group 1 (102 healthy college students; 46 male; 20.40 ± 1.87 years), behavioral results showed that only Future TP was a significant predictor of DD, and higher scores on Future TP were related to lower discounting rates. Whole-brain analysis revealed that steeper discounting correlated with greater GM volume in the ventromedial prefrontal cortex (vmPFC) and ventral part of posterior cingulate cortex (vPCC). Also, GM volume of a cluster in the vmPFC was correlated with Future TP. Interestingly, there was an overlapping region in vmPFC that was correlated with both DD and Future TP. Region-of-interest analysis further indicated that the overlapping region of vmPFC played a partially mediating role in the relation between Future TP and DD in the other independent dataset (Group 2, 36 healthy college students; 14 male; 20.18±1.80 years). Taken together, our results provide a new perspective from neural basis for explaining the relation between DD and future TP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. NMDA antagonist, but not nNOS inhibitor, requires AMPA receptors in the ventromedial prefrontal cortex (vmPFC) to induce antidepressant-like effects

    DEFF Research Database (Denmark)

    Pereira, V. S.; Wegener, Gregers; Joca, S. R.

    2013-01-01

    of the glutamatergic and nitrergic systems of the vmPFC on the behavioral consequences induced by forced swimming (FS), an animal model of depression. Male Wistar rats (230-260g) with guide cannulas aimed at the prelimbic (PL) region of vmPFC were submitted to a 15min session of FS and, 24h later, they were submitted...

  20. sRNAtoolboxVM: Small RNA Analysis in a Virtual Machine.

    Science.gov (United States)

    Gómez-Martín, Cristina; Lebrón, Ricardo; Rueda, Antonio; Oliver, José L; Hackenberg, Michael

    2017-01-01

    High-throughput sequencing (HTS) data for small RNAs (noncoding RNA molecules that are 20-250 nucleotides in length) can now be routinely generated by minimally equipped wet laboratories; however, the bottleneck in HTS-based research has shifted now to the analysis of such huge amount of data. One of the reasons is that many analysis types require a Linux environment but computers, system administrators, and bioinformaticians suppose additional costs that often cannot be afforded by small to mid-sized groups or laboratories. Web servers are an alternative that can be used if the data is not subjected to privacy issues (what very often is an important issue with medical data). However, in any case they are less flexible than stand-alone programs limiting the number of workflows and analysis types that can be carried out.We show in this protocol how virtual machines can be used to overcome those problems and limitations. sRNAtoolboxVM is a virtual machine that can be executed on all common operating systems through virtualization programs like VirtualBox or VMware, providing the user with a high number of preinstalled programs like sRNAbench for small RNA analysis without the need to maintain additional servers and/or operating systems.

  1. Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

    Science.gov (United States)

    Shafford, E A; Rogers, D W; Pritchard, J

    1984-07-01

    Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.

  2. Multiple organ gigantism caused by mutation in VmPPD gene in blackgram (Vigna mungo).

    Science.gov (United States)

    Naito, Ken; Takahashi, Yu; Chaitieng, Bubpa; Hirano, Kumi; Kaga, Akito; Takagi, Kyoko; Ogiso-Tanaka, Eri; Thavarasook, Charaspon; Ishimoto, Masao; Tomooka, Norihiko

    2017-03-01

    Seed size is one of the most important traits in leguminous crops. We obtained a recessive mutant of blackgram that had greatly enlarged leaves, stems and seeds. The mutant produced 100% bigger leaves, 50% more biomass and 70% larger seeds though it produced 40% less number of seeds. We designated the mutant as multiple-organ-gigantism ( mog ) and found the mog phenotype was due to increase in cell numbers but not in cell size. We also found the mog mutant showed a rippled leaf ( rl ) phenotype, which was probably caused by a pleiotropic effect of the mutation. We performed a map-based cloning and successfully identified an 8 bp deletion in the coding sequence of VmPPD gene, an orthologue of Arabidopsis PEAPOD ( PPD ) that regulates arrest of cell divisions in meristematic cells . We found no other mutations in the neighboring genes between the mutant and the wild type. We also knocked down GmPPD genes and reproduced both the mog and rl phenotypes in soybean. Controlling PPD genes to produce the mog phenotype is highly valuable for breeding since larger seed size could directly increase the commercial values of grain legumes.

  3. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  4. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)

    2012-05-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  5. Barbröstade grabbar, med färgat hår och litervis med öl : En analys av Aftonbladets skildring av herr- och damfotboll i Herr-VM 2006 och Dam-VM 2007

    OpenAIRE

    Mårtensson, Henning

    2012-01-01

    I den här uppsatsen har jag undersökt hur män och kvinnor framställs i bild och text i Aftonbladets rapportering från herrarnas fotbolls-VM i Tyskland 2006 och damernas fotbolls-VM i Kina 2007. Mitt syfte var att titta på hur konstrueringen av en nationell diskurs skiljer sig åt i texterna om dam- och herrfotboll, om det finns någon tydlig manlig och kvinnlig diskurs på bilderna, samt hur väl min undersökning stämmer in på beprövade genusteorier. För att kunna besvara mitt syfte använde jag m...

  6. Fast-Solving Quasi-Optimal LS-S3VM Based on an Extended Candidate Set.

    Science.gov (United States)

    Ma, Yuefeng; Liang, Xun; Kwok, James T; Li, Jianping; Zhou, Xiaoping; Zhang, Haiyan

    2018-04-01

    The semisupervised least squares support vector machine (LS-S 3 VM) is an important enhancement of least squares support vector machines in semisupervised learning. Given that most data collected from the real world are without labels, semisupervised approaches are more applicable than standard supervised approaches. Although a few training methods for LS-S 3 VM exist, the problem of deriving the optimal decision hyperplane efficiently and effectually has not been solved. In this paper, a fully weighted model of LS-S 3 VM is proposed, and a simple integer programming (IP) model is introduced through an equivalent transformation to solve the model. Based on the distances between the unlabeled data and the decision hyperplane, a new indicator is designed to represent the possibility that the label of an unlabeled datum should be reversed in each iteration during training. Using the indicator, we construct an extended candidate set consisting of the indices of unlabeled data with high possibilities, which integrates more information from unlabeled data. Our algorithm is degenerated into a special scenario of the previous algorithm when the extended candidate set is reduced into a set with only one element. Two strategies are utilized to determine the descent directions based on the extended candidate set. Furthermore, we developed a novel method for locating a good starting point based on the properties of the equivalent IP model. Combined with the extended candidate set and the carefully computed starting point, a fast algorithm to solve LS-S 3 VM quasi-optimally is proposed. The choice of quasi-optimal solutions results in low computational cost and avoidance of overfitting. Experiments show that our algorithm equipped with the two designed strategies is more effective than other algorithms in at least one of the following three aspects: 1) computational complexity; 2) generalization ability; and 3) flexibility. However, our algorithm and other algorithms have

  7. vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

    Science.gov (United States)

    Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca E; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

    2017-07-01

    Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Progenitor's Signatures in Type Ia Supernova Remnants

    NARCIS (Netherlands)

    Chiotellis, A.; Kosenko, D.; Schure, K.M.; Vink, J.

    2013-01-01

    The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that

  9. Pulpal progenitors and dentin repair.

    Science.gov (United States)

    Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A

    2011-07-01

    Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.

  10. Engineering the CernVM-Filesystem as a High Bandwidth Distributed Filesystem for Auxiliary Physics Data

    Science.gov (United States)

    Dykstra, D.; Bockelman, B.; Blomer, J.; Herner, K.; Levshina, T.; Slyz, M.

    2015-12-01

    A common use pattern in the computing models of particle physics experiments is running many distributed applications that read from a shared set of data files. We refer to this data is auxiliary data, to distinguish it from (a) event data from the detector (which tends to be different for every job), and (b) conditions data about the detector (which tends to be the same for each job in a batch of jobs). Relatively speaking, conditions data also tends to be relatively small per job where both event data and auxiliary data are larger per job. Unlike event data, auxiliary data comes from a limited working set of shared files. Since there is spatial locality of the auxiliary data access, the use case appears to be identical to that of the CernVM- Filesystem (CVMFS). However, we show that distributing auxiliary data through CVMFS causes the existing CVMFS infrastructure to perform poorly. We utilize a CVMFS client feature called "alien cache" to cache data on existing local high-bandwidth data servers that were engineered for storing event data. This cache is shared between the worker nodes at a site and replaces caching CVMFS files on both the worker node local disks and on the site's local squids. We have tested this alien cache with the dCache NFSv4.1 interface, Lustre, and the Hadoop Distributed File System (HDFS) FUSE interface, and measured performance. In addition, we use high-bandwidth data servers at central sites to perform the CVMFS Stratum 1 function instead of the low-bandwidth web servers deployed for the CVMFS software distribution function. We have tested this using the dCache HTTP interface. As a result, we have a design for an end-to-end high-bandwidth distributed caching read-only filesystem, using existing client software already widely deployed to grid worker nodes and existing file servers already widely installed at grid sites. Files are published in a central place and are soon available on demand throughout the grid and cached locally on the

  11. Engineering the CernVM-Filesystem as a High Bandwidth Distributed Filesystem for Auxiliary Physics Data

    Energy Technology Data Exchange (ETDEWEB)

    Dykstra, D. [Fermilab; Bockelman, B. [Nebraska U.; Blomer, J. [CERN; Herner, K. [Fermilab; Levshina, T. [Fermilab; Slyz, M. [Fermilab

    2015-12-23

    A common use pattern in the computing models of particle physics experiments is running many distributed applications that read from a shared set of data files. We refer to this data is auxiliary data, to distinguish it from (a) event data from the detector (which tends to be different for every job), and (b) conditions data about the detector (which tends to be the same for each job in a batch of jobs). Relatively speaking, conditions data also tends to be relatively small per job where both event data and auxiliary data are larger per job. Unlike event data, auxiliary data comes from a limited working set of shared files. Since there is spatial locality of the auxiliary data access, the use case appears to be identical to that of the CernVM- Filesystem (CVMFS). However, we show that distributing auxiliary data through CVMFS causes the existing CVMFS infrastructure to perform poorly. We utilize a CVMFS client feature called 'alien cache' to cache data on existing local high-bandwidth data servers that were engineered for storing event data. This cache is shared between the worker nodes at a site and replaces caching CVMFS files on both the worker node local disks and on the site's local squids. We have tested this alien cache with the dCache NFSv4.1 interface, Lustre, and the Hadoop Distributed File System (HDFS) FUSE interface, and measured performance. In addition, we use high-bandwidth data servers at central sites to perform the CVMFS Stratum 1 function instead of the low-bandwidth web servers deployed for the CVMFS software distribution function. We have tested this using the dCache HTTP interface. As a result, we have a design for an end-to-end high-bandwidth distributed caching read-only filesystem, using existing client software already widely deployed to grid worker nodes and existing file servers already widely installed at grid sites. Files are published in a central place and are soon available on demand throughout the grid and cached

  12. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  13. Autosomal dominant inheritance of brain cardiolipin fatty acid abnormality in VM/DK mice: association with hypoxic-induced cognitive insensitivity.

    Science.gov (United States)

    Ta, Nathan L; Jia, Xibei; Kiebish, Michael; Seyfried, Thomas N

    2014-01-01

    Cardiolipin is a complex polyglycerol phospholipid found almost exclusively in the inner mitochondrial membrane and regulates numerous enzyme activities especially those related to oxidative phosphorylation and coupled respiration. Abnormalities in cardiolipin can impair mitochondrial function and bioenergetics. We recently demonstrated that the ratio of shorter chain saturated and monounsaturated fatty acids (C16:0; C18:0; C18:1) to longer chain polyunsaturated fatty acids (C18:2; C20:4; C22:6) was significantly greater in the brains of adult VM/DK (VM) inbred mice than in the brains of C57BL/6 J (B6) mice. The cardiolipin fatty acid abnormalities in VM mice are also associated with alterations in the activity of mitochondrial respiratory complexes. In this study we found that the abnormal brain fatty acid ratio in the VM strain was inherited as an autosomal dominant trait in reciprocal B6 × VM F1 hybrids. To evaluate the potential influence of brain cardiolipin fatty acid composition on cognitive sensitivity, we placed the parental B6 and VM mice and their reciprocal male and female B6VMF1 hybrid mice (3-month-old) in a hypoxic chamber (5 % O2). Cognitive awareness (conscientiousness) under hypoxia was significantly lower in the VM parental mice and F1 hybrid mice (11.4 ± 0.4  and 11.0 ± 0.4 min, respectively) than in the parental B6 mice (15.3 ± 1.4 min), indicating an autosomal dominant inheritance like that of the brain cardiolipin abnormalities. These findings suggest that impaired cognitive awareness under hypoxia is associated with abnormalities in neural lipid composition.

  14. Optimizing VM allocation and data placement for data-intensive applications in cloud using ACO metaheuristic algorithm

    Directory of Open Access Journals (Sweden)

    T.P. Shabeera

    2017-04-01

    Full Text Available Nowadays data-intensive applications for processing big data are being hosted in the cloud. Since the cloud environment provides virtualized resources for computation, and data-intensive applications require communication between the computing nodes, the placement of Virtual Machines (VMs and location of data affect the overall computation time. Majority of the research work reported in the current literature consider the selection of physical nodes for placing data and VMs as independent problems. This paper proposes an approach which considers VM placement and data placement hand in hand. The primary objective is to reduce cross network traffic and bandwidth usage, by placing required number of VMs and data in Physical Machines (PMs which are physically closer. The VM and data placement problem (referred as MinDistVMDataPlacement problem is defined in this paper and has been proved to be NP- Hard. This paper presents and evaluates a metaheuristic algorithm based on Ant Colony Optimization (ACO, which selects a set of adjacent PMs for placing data and VMs. Data is distributed in the physical storage devices of the selected PMs. According to the processing capacity of each PM, a set of VMs are placed on these PMs to process data stored in them. We use simulation to evaluate our algorithm. The results show that the proposed algorithm selects PMs in close proximity and the jobs executed in the VMs allocated by the proposed scheme outperforms other allocation schemes.

  15. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  16. Radiation-induced conduction under high electric field (1 x 106 to 1 x 108 V/m) in polyethylene-terephthalate

    International Nuclear Information System (INIS)

    Maeda, H.; Kurashige, M.; Ito, D.; Nakakita, T.

    1978-01-01

    Radiation-induced conduction in polyethylene-terephthalate (PET) has been measured under high electric field (1.0 x 10 6 to 1.6 x 10 8 V/m). In a 6-μm-thick PET film, saturation of the radiation-induced current occurs at field strengths above 1.2 x 10 8 V/m. This has been demonstrated by the thickness and dose rate dependence of the induced current. Radiation-induced conductivity increases monotonically with field strength, then shows a saturation tendency. This may be explained by geminate recombination. Above 1 x 10 8 V/m, slowly increasing radiation-induced current appears. This may be caused by electron injection from the cathode, enhanced by the accumulation of the hetero space charges near it

  17. CernVM Co-Pilot: an Extensible Framework for Building Scalable Computing Infrastructures on the Cloud

    Science.gov (United States)

    Harutyunyan, A.; Blomer, J.; Buncic, P.; Charalampidis, I.; Grey, F.; Karneyeu, A.; Larsen, D.; Lombraña González, D.; Lisec, J.; Segal, B.; Skands, P.

    2012-12-01

    CernVM Co-Pilot is a framework for instantiating an ad-hoc computing infrastructure on top of managed or unmanaged computing resources. Co-Pilot can either be used to create a stand-alone computing infrastructure, or to integrate new computing resources into existing infrastructures (such as Grid or batch). Unlike traditional middleware systems, Co-Pilot components communicate using the Extensible Messaging and Presence protocol (XMPP). This allows the system to be easily scaled in case of a high load, and it also simplifies the development of new components. In this contribution we present the latest developments and the current status of the framework, discuss how it can be extended to suit the needs of a particular community, as well as describe the operational experience of using the framework in the LHC@home 2.0 volunteer computing project.

  18. CernVM Co-Pilot: a Framework for Orchestrating Virtual Machines Running Applications of LHC Experiments on the Cloud

    International Nuclear Information System (INIS)

    Harutyunyan, A; Sánchez, C Aguado; Blomer, J; Buncic, P

    2011-01-01

    CernVM Co-Pilot is a framework for the delivery and execution of the workload on remote computing resources. It consists of components which are developed to ease the integration of geographically distributed resources (such as commercial or academic computing clouds, or the machines of users participating in volunteer computing projects) into existing computing grid infrastructures. The Co-Pilot framework can also be used to build an ad-hoc computing infrastructure on top of distributed resources. In this paper we present the architecture of the Co-Pilot framework, describe how it is used to execute the jobs of the ALICE and ATLAS experiments, as well as to run the Monte-Carlo simulation application of CERN Theoretical Physics Group.

  19. Acceptance of the 2014 V.M. Goldschmidt Award of the Gochemical Society by Timothy L. Grove

    Science.gov (United States)

    Grove, Timothy L.

    2015-06-01

    I am deeply honored to be the recipient of the 2014 V.M. Goldschmidt Award. Many of the past recipients of this award have been scientific heroes to me, and it is hard to express how it feels to be included in this distinguished group. My feelings run the full spectrum; from exhilaration and deep personal satisfaction for the recognition of the work that I have done, to humility and anxiety that maybe I am really not good enough to deserve this award. This is called impostor syndrome. You younger scientists should know that many of us, even those who appear very successful, still experience it - don't let it hold you back.

  20. CernVM Co-Pilot: an Extensible Framework for Building Scalable Computing Infrastructures on the Cloud

    International Nuclear Information System (INIS)

    Harutyunyan, A; Blomer, J; Buncic, P; Charalampidis, I; Grey, F; Karneyeu, A; Larsen, D; Lombraña González, D; Lisec, J; Segal, B; Skands, P

    2012-01-01

    CernVM Co-Pilot is a framework for instantiating an ad-hoc computing infrastructure on top of managed or unmanaged computing resources. Co-Pilot can either be used to create a stand-alone computing infrastructure, or to integrate new computing resources into existing infrastructures (such as Grid or batch). Unlike traditional middleware systems, Co-Pilot components communicate using the Extensible Messaging and Presence protocol (XMPP). This allows the system to be easily scaled in case of a high load, and it also simplifies the development of new components. In this contribution we present the latest developments and the current status of the framework, discuss how it can be extended to suit the needs of a particular community, as well as describe the operational experience of using the framework in the LHC at home 2.0 volunteer computing project.

  1. Inhibition of xyloglucanase from an alkalothermophilic Thermomonospora sp. by a peptidic aspartic protease inhibitor from Penicillium sp. VM24.

    Science.gov (United States)

    Menon, Vishnu; Rao, Mala

    2012-11-01

    A bifunctional inhibitor from Penicillium sp VM24 causing inactivation of xyloglucanase from Thermomonospora sp and an aspartic protease from Aspergillus saitoi was identified. Steady state kinetics studies of xyloglucanase and the inhibitor revealed an irreversible, non-competitive, two-step inhibition mechanism with IC(50) and K(i) values of 780 and 500nM respectively. The interaction of o-phthalaldehyde (OPTA)-labeled xyloglucanase with the inhibitor revealed that the inhibitor binds to the active site of the enzyme. Far- and near-UV spectrophotometric analysis suggests that the conformational changes induced in xyloglucanase by the inhibitor may be due to irreversible denaturation of enzyme. The bifunctional inhibitor may have potential as a biocontrol agent for the protection of plants against phytopathogenic fungi. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Postglacial Rebound and Current Ice Loss Estimates from Space Geodesy: The New ICE-6G (VM5a) Global Model

    Science.gov (United States)

    Peltier, W. R.; Argus, D.; Drummond, R.; Moore, A. W.

    2012-12-01

    We compare, on a global basis, estimates of site velocity against predictions of the newly constructed postglacial rebound model ICE-6G (VM5a). This model is fit to observations of North American postglacial rebound thereby demonstrating that the ice sheet at last glacial maximum must have been, relative to ICE-5G,thinner in southern Manitoba, thinner near Yellowknife (northwest Territories), thicker in eastern and southern Quebec, and thicker along the British Columbia-Alberta border. The GPS based estimates of site velocity that we employ are more accurate than were previously available because they are based on GPS estimates of position as a function of time determined by incorporating satellite phase center variations [Desai et al. 2011]. These GPS estimates are constraining postglacial rebound in North America and Europe more tightly than ever before. In particular, given the high density of GPS sites in North America, and the fact that the velocity of the mass center (CM) of Earth is also more tightly constrained, the new model much more strongly constrains both the lateral extent of the proglacial forebulge and the rate at which this peripheral bulge (that was emplaced peripheral to the late Pleistocence Laurentia ice sheet) is presently collapsing. This fact proves to be important to the more accurate inference of the current rate of ice loss from both Greenland and Alaska based upon the time dependent gravity observations being provided by the GRACE satellite system. In West Antarctica we have also been able to significantly revise the previously prevalent ICE-5G deglaciation history so as to enable its predictions to be optimally consistent with GPS site velocities determined by connecting campaign WAGN measurements to those provided by observations from the permanent ANET sites. Ellsworth Land (south of the Antarctic peninsula), is observed to be rising at 6 ±3 mm/yr according to our latest analyses; the Ellsworth mountains themselves are observed to be

  3. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  4. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  5. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  6. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    Directory of Open Access Journals (Sweden)

    A M Poff

    Full Text Available The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control, low glucose (LG, ketone supplementation (βHB, hyperbaric oxygen (HBOT, or combination therapy (LG+βHB+HBOT on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  7. Cataclysmic Variables as Supernova Ia Progenitors

    Directory of Open Access Journals (Sweden)

    Stella Kafka

    2012-06-01

    Full Text Available Although the identification of the progenitors of type Ia supernovae (SNeIa remains controversial, it is generally accepted that they originate from binary star systems in which at least one component is a carbon-oxygen white dwarf (WD; those systems are grouped under the wide umbrella of cataclysmic variables. Current theories for SNeIa progenitors hold that, either via Roche lobe overflow of the companion or via a wind, the WD accumulates hydrogen or helium rich material which is then burned to C and O onto the WD’s surface. However, the specifics of this scenario are far from being understood or defined, allowing for a wealth of theories fighting for attention and a dearth of observations to support them. I discuss the latest attempts to identify and study those controversial SNeIa progenitors. I also introduce the most promising progenitor in hand and I present observational diagnostics that can reveal more members of the category.

  8. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo; Pagliari, Francesca

    2017-01-01

    by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient

  9. The ICE-6G_C (VM5a) Global Model of the GIA Process: Antarctica at High Spatial Resolution

    Science.gov (United States)

    Peltier, W. R.; Drummond, R.; Argus, D. F.

    2016-12-01

    The ICE-6G_C (VM5a) global model of the glacial isostatic adjustment process (Argus et al., 2014 GJI 198, 537-563; Peltier et al. , 2015, JGR 119, doi:10.1002/2014JB011176) is the latest model in the ICE-nG (VMx) sequence. The model continues to be unique in that it is the only model whose properties are made freely available at each iterative step in its development. This latest version, which embodies detailed descriptions of the Laurentide , Fennoscandian/Barents Sea, Greenland and Antarctic ice sheets through the most recent glacial cycle, is a refinement based primarily upon the incorporation of the constraints being provided by GPS measurements of the vertical and horizontal motion of the crust as well as GRACE observations of the time dependent gravity field. The model has been shown to provide exceptionally accurate predictions of these space geodetic observations of the response to the most recent Late Quaternary glacial cycle. Particular attention has been paid to the Antarctic component as it is well known on the basis of analyses of the sedimentary stratigraphy off-shore and geomorphological characteristics of the continental shelf, that the Last Glacial Maximum state of the southern continent was one in which grounded ice extended out to the shelf break in most locations, including significant fractions of the Ross Sea and Weddell Sea embayments. In the latter regions especially, it is expected that grounded ice would have existed below sea level. In ICE-6G_C (VM5a) a grounding line tracking algorithm was employed (Stuhne and Peltier, 2015 JGR 120, 1841-1865) in order to describe the unloading of the solid surface by ice that was initially grounded below sea level, an apparently unique characteristic of this model. In the initially published version, in which the Sea Level Equation (SLE) was inverted on a basis of spherical harmonics truncated at degree and order 256, this led to "ringing" in the embayments when the Stokes coefficients of the model

  10. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  11. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  12. PROOF as a Service on the Cloud: a Virtual Analysis Facility based on the CernVM ecosystem

    CERN Document Server

    Berzano, Dario; Buncic, Predrag; Charalampidis, Ioannis; Ganis, Gerardo; Lestaris, Georgios; Meusel, René

    2014-01-01

    PROOF, the Parallel ROOT Facility, is a ROOT-based framework which enables interactive parallelism for event-based tasks on a cluster of computing nodes. Although PROOF can be used simply from within a ROOT session with no additional requirements, deploying and configuring a PROOF cluster used to be not as straightforward. Recently great efforts have been spent to make the provisioning of generic PROOF analysis facilities with zero configuration, with the added advantages of positively affecting both stability and scalability, making the deployment operations feasible even for the end user. Since a growing amount of large-scale computing resources are nowadays made available by Cloud providers in a virtualized form, we have developed the Virtual PROOF-based Analysis Facility: a cluster appliance combining the solid CernVM ecosystem and PoD (PROOF on Demand), ready to be deployed on the Cloud and leveraging some peculiar Cloud features such as elasticity. We will show how this approach is effective both for sy...

  13. PROOF as a service on the cloud: a virtual analysis facility based on the CernVM ecosystem

    International Nuclear Information System (INIS)

    Berzano, D; Blomer, J; Buncic, P; Charalampidis, I; Ganis, G; Lestaris, G; Meusel, R

    2014-01-01

    PROOF, the Parallel ROOT Facility, is a ROOT-based framework which enables interactive parallelism for event-based tasks on a cluster of computing nodes. Although PROOF can be used simply from within a ROOT session with no additional requirements, deploying and configuring a PROOF cluster used to be not as straightforward. Recently great efforts have been spent to make the provisioning of generic PROOF analysis facilities with zero configuration, with the added advantages of positively affecting both stability and scalability, making the deployment operations feasible even for the end user. Since a growing amount of large-scale computing resources are nowadays made available by Cloud providers in a virtualized form, we have developed the Virtual PROOF-based Analysis Facility: a cluster appliance combining the solid CernVM ecosystem and PoD (PROOF on Demand), ready to be deployed on the Cloud and leveraging some peculiar Cloud features such as elasticity. We will show how this approach is effective both for sysadmins, who will have little or no configuration to do to run it on their Clouds, and for the end users, who are ultimately in full control of their PROOF cluster and can even easily restart it by themselves in the unfortunate event of a major failure. We will also show how elasticity leads to a more optimal and uniform usage of Cloud resources.

  14. Activity in dlPFC and its effective connectivity to vmPFC are associated with temporal discounting

    Directory of Open Access Journals (Sweden)

    Todd A Hare

    2014-03-01

    Full Text Available There is widespread interest in identifying computational and neurobiological mechanisms that influence the ability to choose long-term benefits over more proximal and readily available rewards in domains such as dietary and economic choice. We present the results of a human fMRI study that examines how neural activity relates to observed individual differences in the discounting of future rewards during an intertemporal monetary choice task. We found that a region of left dlPFC BA-46 was more active in trials where subjects chose delayed rewards, after controlling for the subjective value of those rewards. We also found that the connectivity from dlPFC BA-46 to a region of vmPFC widely associated with the computational of stimulus values, increased at the time of choice, and especially during trials in which subjects chose delayed rewards. Finally, we found that estimates of effective connectivity between these two regions played a critical role in predicting out-of-sample, between-subject differences in discount rates. Together with previous findings in dietary choice, these results suggest that a common set of computational and neurobiological mechanisms facilitate choices in favor of long- term reward in both settings.

  15. A New Resources Provisioning Method Based on QoS Differentiation and VM Resizing in IaaS

    Directory of Open Access Journals (Sweden)

    Rongdong Hu

    2015-01-01

    Full Text Available In order to improve the host energy efficiency in IaaS, we proposed an adaptive host resource provisioning method, CoST, which is based on QoS differentiation and VM resizing. The control model can adaptively adjust control parameters according to real time application performance, in order to cope with changes in load. CoST takes advantage of the fact that different types of applications have different sensitivity degrees to performance and cost. It places two different types of VMs on the same host and dynamically adjusts their sizes based on the load forecasting and QoS feedback. It not only guarantees the performance defined in SLA, but also keeps the host running in energy-efficient state. Real Google cluster trace and host power data are used to evaluate the proposed method. Experimental results show that CoST can provide performance-sensitive application with a steady QoS and simultaneously speed up the overall processing of performance-tolerant application by 20~66%. The host energy efficiency is significantly improved by 7~23%.

  16. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-01-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  17. THE AGES OF TYPE Ia SUPERNOVA PROGENITORS

    International Nuclear Information System (INIS)

    Brandt, Timothy D.; Aubourg, Eric; Strauss, Michael A.; Tojeiro, Rita; Heavens, Alan; Jimenez, Raul

    2010-01-01

    Using light curves and host galaxy spectra of 101 Type Ia supernovae (SNe Ia) with redshift z ∼ 2.4 Gyr. We find that each channel contributes roughly half of the Type Ia rate in our reference sample. We also construct the average spectra of high-stretch and low-stretch SN Ia host galaxies, and find that the difference of these spectra looks like a main-sequence B star with nebular emission lines indicative of star formation. This supports our finding that there are two populations of SNe Ia, and indicates that the progenitors of high-stretch supernovae are at the least associated with very recent star formation in the last few tens of Myr. Our results provide valuable constraints for models of Type Ia progenitors and may help improve the calibration of SNe Ia as standard candles.

  18. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  19. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    Science.gov (United States)

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation

    DEFF Research Database (Denmark)

    Jensen, P B; Roed, H; Skovsgaard, T

    1990-01-01

    doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg...... the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross......-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo....

  1. Observational Investigations of the Progenitors of Supernovae

    Science.gov (United States)

    Lyman, J. D.

    2014-03-01

    Supernovae (SNe) are the spectacular deaths of stars and have shaped the universe we see today. Their far-reaching influence affects the chemical and dynamical evolution of galaxies, star formation, neutron star and black hole formation, and they are largely responsible for most of the heavy elements that make up the universe, including around 90 per cent of the reader. They also provide laboratories of nuclear and particle physics far beyond what we can construct on Earth and act as probes of extreme density and energy. This thesis presents new research into understanding the nature of the progenitor systems of various types of SNe, as well as presenting results that will allow their study to be more productive in the future, through use of automated pipelines and methods to increase the science value of discovered SNe. An environmental study of two peculiar types of transients ('Calcium-rich' and '2002cx-like'), which may not be true SNe, reveals extremely different ages of the exploding systems that will constrain the current theoretical effort into discovering the progenitor systems. The GRB-SN 120422A/2012bz is investigated and found to be an extremely luminous and energetic SN, even amongst the infamously bright GRB-SNe. A method is presented that allows an accurate reconstruction of the bolometric light curve of a core-collapse SN, which relies on only two optical filter observations - this will hugely reduce the observational cost of constructing bolometric light curves, a tool of great importance when hoping to constrain the nature of a SN explosion and hence its progenitor. Finally, this method is utilised to construct the largest bolometric CCSN bolometric light curve sample to date, and these are analytically modelled to reveal population statistics of the explosions, thus informing on the nature of the progenitors.

  2. EVOLUTION OF PROGENITORS FOR ELECTRON CAPTURE SUPERNOVAE

    International Nuclear Information System (INIS)

    Takahashi, Koh; Umeda, Hideyuki; Yoshida, Takashi

    2013-01-01

    We provide progenitor models for electron capture supernovae (ECSNe) with detailed evolutionary calculation. We include minor electron capture nuclei using a large nuclear reaction network with updated reaction rates. For electron capture, the Coulomb correction of rates is treated and the contribution from neutron-rich isotopes is taken into account in each nuclear statistical equilibrium (NSE) composition. We calculate the evolution of the most massive super asymptotic giant branch stars and show that these stars undergo off-center carbon burning and form ONe cores at the center. These cores become heavier up to the critical mass of 1.367 M ☉ and keep contracting even after the initiation of O+Ne deflagration. Inclusion of minor electron capture nuclei causes convective URCA cooling during the contraction phase, but the effect on the progenitor evolution is small. On the other hand, electron capture by neutron-rich isotopes in the NSE region has a more significant effect. We discuss the uniqueness of the critical core mass for ECSNe and the effect of wind mass loss on the plausibility of our models for ECSN progenitors.

  3. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  4. Constraining models of postglacial rebound using space geodesy: a detailed assessment of model ICE-5G (VM2) and its relatives

    Science.gov (United States)

    Argus, Donald F.; Peltier, W. Richard

    2010-05-01

    Using global positioning system, very long baseline interferometry, satellite laser ranging and Doppler Orbitography and Radiopositioning Integrated by Satellite observations, including the Canadian Base Network and Fennoscandian BIFROST array, we constrain, in models of postglacial rebound, the thickness of the ice sheets as a function of position and time and the viscosity of the mantle as a function of depth. We test model ICE-5G VM2 T90 Rot, which well fits many hundred Holocene relative sea level histories in North America, Europe and worldwide. ICE-5G is the deglaciation history having more ice in western Canada than ICE-4G; VM2 is the mantle viscosity profile having a mean upper mantle viscosity of 0.5 × 1021Pas and a mean uppermost-lower mantle viscosity of 1.6 × 1021Pas T90 is an elastic lithosphere thickness of 90 km; and Rot designates that the model includes (rotational feedback) Earth's response to the wander of the North Pole of Earth's spin axis towards Canada at a speed of ~1° Myr-1. The vertical observations in North America show that, relative to ICE-5G, the Laurentide ice sheet at last glacial maximum (LGM) at ~26 ka was (1) much thinner in southern Manitoba, (2) thinner near Yellowknife (Northwest Territories), (3) thicker in eastern and southern Quebec and (4) thicker along the northern British Columbia-Alberta border, or that ice was unloaded from these areas later (thicker) or earlier (thinner) than in ICE-5G. The data indicate that the western Laurentide ice sheet was intermediate in mass between ICE-5G and ICE-4G. The vertical observations and GRACE gravity data together suggest that the western Laurentide ice sheet was nearly as massive as that in ICE-5G but distributed more broadly across northwestern Canada. VM2 poorly fits the horizontal observations in North America, predicting places along the margins of the Laurentide ice sheet to be moving laterally away from the ice centre at 2 mm yr-1 in ICE-4G and 3 mm yr-1 in ICE-5G, in

  5. ARC-VM: An architecture real options complexity-based valuation methodology for military systems-of-systems acquisitions

    Science.gov (United States)

    Domercant, Jean Charles

    The combination of today's national security environment and mandated acquisition policies makes it necessary for military systems to interoperate with each other to greater degrees. This growing interdependency results in complex Systems-of-Systems (SoS) that only continue to grow in complexity to meet evolving capability needs. Thus, timely and affordable acquisition becomes more difficult, especially in the face of mounting budgetary pressures. To counter this, architecting principles must be applied to SoS design. The research objective is to develop an Architecture Real Options Complexity-Based Valuation Methodology (ARC-VM) suitable for acquisition-level decision making, where there is a stated desire for more informed tradeoffs between cost, schedule, and performance during the early phases of design. First, a framework is introduced to measure architecture complexity as it directly relates to military SoS. Development of the framework draws upon a diverse set of disciplines, including Complexity Science, software architecting, measurement theory, and utility theory. Next, a Real Options based valuation strategy is developed using techniques established for financial stock options that have recently been adapted for use in business and engineering decisions. The derived complexity measure provides architects with an objective measure of complexity that focuses on relevant complex system attributes. These attributes are related to the organization and distribution of SoS functionality and the sharing and processing of resources. The use of Real Options provides the necessary conceptual and visual framework to quantifiably and traceably combine measured architecture complexity, time-valued performance levels, as well as programmatic risks and uncertainties. An example suppression of enemy air defenses (SEAD) capability demonstrates the development and usefulness of the resulting architecture complexity & Real Options based valuation methodology. Different

  6. Performance evaluation of the General Electric eXplore CT 120 micro-CT using the vmCT phantom

    Energy Technology Data Exchange (ETDEWEB)

    Bahri, M.A., E-mail: M.Bahri@ulg.ac.be [ULg-Liege University, Cyclotron Research Centre, Liege, Bat. 30, Allee du 6 aout, 8 (Belgium); Warnock, G.; Plenevaux, A. [ULg-Liege University, Cyclotron Research Centre, Liege, Bat. 30, Allee du 6 aout, 8 (Belgium); Choquet, P.; Constantinesco, A. [Biophysique et Medecine Nucleaire, Hopitaux universitaires de Strasbourg, Strasbourg (France); Salmon, E.; Luxen, A. [ULg-Liege University, Cyclotron Research Centre, Liege, Bat. 30, Allee du 6 aout, 8 (Belgium); Seret, A. [ULg-Liege University, Cyclotron Research Centre, Liege, Bat. 30, Allee du 6 aout, 8 (Belgium); ULg-Liege University, Experimental Medical Imaging, Liege (Belgium)

    2011-08-21

    The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high-power tube and a flat-panel detector. It allows high resolution and high contrast fast CT scanning of small animals. The aim of this study was to compare the performance of the eXplore CT 120 with that of the eXplore Ultra, its predecessor for which the methodology using the vmCT phantom has already been described . The phantom was imaged using typical a rat (fast scan or F) or mouse (in vivo bone scan or H) scanning protocols. With the slanted edge method, a 10% modulation transfer function (MTF) was observed at 4.4 (F) and 3.9-4.4 (H) mm{sup -1} corresponding to 114 {mu}m resolution. A fairly larger MTF was obtained by the coil method with the MTF for the thinnest coil (3.3 mm{sup -1}) equal to 0.32 (F) and 0.34 (H). The geometric accuracy was better than 0.3%. There was a highly linear (R{sup 2}>0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom. A cupping effect was clearly seen on the uniform slices and the uniformity-to-noise ratio ranged from 0.52 (F) to 0.89 (H). The air CT number depended on the amount of polycarbonate surrounding the area where it was measured; a difference as high as approximately 200 HU was observed. This hindered the calibration of this scanner in HU. This is likely due to the absence of corrections for beam hardening and scatter in the reconstruction software. However in view of the high linearity of the system, the implementation of these corrections would allow a good quality calibration of the scanner in HU. In conclusion, the eXplore CT 120 achieved a better spatial resolution than the eXplore Ultra (based on previously reported specifications) and future software developments will include beam hardening and scatter corrections that will make the new generation CT scanner even more promising.

  7. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B

    2005-01-01

    To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.......To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs....

  8. Selective uptake of boronophenylalanine by glioma stem/progenitor cells

    International Nuclear Information System (INIS)

    Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei

    2012-01-01

    The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.

  9. Neuroanatomy of the vmPFC and dlPFC predicts individual differences in cognitive regulation during dietary self-control across regulation strategies.

    Science.gov (United States)

    Schmidt, Liane; Tusche, Anita; Manoharan, Nicolas; Hutcherson, Cendri; Hare, Todd; Plassmann, Hilke

    2018-06-04

    Making healthy food choices is challenging for many people. Individuals differ greatly in their ability to follow health goals in the face of temptation, but it is unclear what underlies such differences. Using voxel-based morphometry (VBM), we investigated in healthy humans (i.e., men and women) links between structural variation in gray matter volume and individuals' level of success in shifting toward healthier food choices. We combined MRI and choice data into a joint dataset by pooling across three independent studies that employed a task prompting participants to explicitly focus on the healthiness of food items before making their food choices. Within this dataset, we found that individual differences in gray matter volume in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) predicted regulatory success. We extended and confirmed these initial findings by predicting regulatory success out of sample and across tasks in a second dataset requiring participants to apply a different regulation strategy that entailed distancing from cravings for unhealthy, appetitive foods. Our findings suggest that neuroanatomical markers in the vmPFC and dlPFC generalized to different forms of dietary regulation strategies across participant groups. They provide novel evidence that structural differences in neuroanatomy of two key regions for valuation and its control, the vmPFC and dlPFC, predict an individual's ability to exert control in dietary choices. SIGNIFICANCE STATEMENT Dieting involves regulating food choices in order to eat healthier foods and fewer unhealthy foods. People differ dramatically in their ability to achieve or maintain this regulation, but it is unclear why. Here, we show that individuals with more gray matter volume in the dorsolateral and ventromedial prefrontal cortex are better at exercising dietary self-control. This relationship was observed across four different studies examining two different forms of dietary

  10. Impairment of circulating endothelial progenitors in Down syndrome

    Directory of Open Access Journals (Sweden)

    Costa Valerio

    2010-09-01

    Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered

  11. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    Gelovani, Juri G.

    2008-01-01

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  12. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo

    2017-02-22

    For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated. Further studies are needed to fully exploit this cell population, but, sampling auricles, it could be possible to treat cardiac patients using their own cells circumventing rejection or organ shortage limitations.

  13. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  14. Cytokinetics and Regulation of Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lajtha, L. G. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

    1967-07-15

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  15. A COMPREHENSIVE PROGENITOR MODEL FOR SNe Ia

    International Nuclear Information System (INIS)

    Meng, X.; Yang, W.

    2010-01-01

    Although the nature of the progenitor of Type Ia supernovae (SNe Ia) is still unclear, the single-degenerate (SD) channel for the progenitor is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit, and then explodes as an SN Ia. The companion may be a main sequence or a slightly evolved star (WD + MS), or a red giant star (WD + RG). Incorporating the effect of mass stripping and accretion-disk instability on the evolution of the WD binary, we carried out binary stellar evolution calculations for more than 1600 close WD binaries. As a result, the initial parameter spaces for SNe Ia are presented in an orbital period-secondary mass (log P i , M i 2 ) plane. We confirmed that in a WD + MS system, the initial companion leading to SNe Ia may have mass from 1 M sun to 5 M sun . The initial WD mass for SNe Ia from WD + MS channel is as low as 0.565 M sun , while the lowest WD mass from the WD + RG channel is 1.0 M sun . Adopting the above results, we studied the birth rate of SNe Ia via a binary population synthesis approach. We found that the Galactic SNe Ia birth rate from SD model is (2.55-2.9) x 10 -3 yr -1 (including WD + He star channel), which is slightly smaller than that from observation. If a single starburst is assumed, the distribution of the delay time of SNe Ia from the SD model may be a weak bimodality, where WD + He channel contributes to SNe Ia with delay time shorter than 10 8 yr and WD + RG channel to those with age longer than 6 Gyr.

  16. Cytokinetics and Regulation of Progenitor Cells

    International Nuclear Information System (INIS)

    Lajtha, L.G.

    1967-01-01

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  17. Comment on "An Assessment of the ICE-6G_C (VM5a) Glacial Isostatic Adjustment Model" by Purcell et al.

    Science.gov (United States)

    Richard Peltier, W.; Argus, Donald F.; Drummond, Rosemarie

    2018-02-01

    The most recently published model of the glacial isostatic adjustment process in the ICE-NG (VMX) sequence from the University of Toronto, denoted ICE-6G_C (VM5a), was originally developed to degree and order 256 in spherical harmonics and has been shown to provide accurate fits to a voluminous database of GPS observations from North America, Eurasia, and Antarctica, to time dependent gravity data being provided by the GRACE satellites, and to radiocarbon-dated relative sea level histories through the Holocene epoch. The authors of the Purcell et al. (2016, https://doi.org/10.1002/2015JB012742) paper have suggested this model to be flawed. We have produced a further version of our model, denoted ICE-6G_D (VM5a), by employing the same BEDMAP2 bathymetry for the Southern Ocean as employed in their analysis which has somewhat reduced the differences between our results. However, significant physically important differences remain, including the magnitude of present-day vertical crustal motion in the embayments and in the spectrum of Stokes coefficients for present-day geoid height time dependence which continues to "flatten" at high spherical harmonic degree. We explore the reasons for these differences and trace them to the use by Purcell et al. of a loading history for the embayments that differs significantly from that tabulated for both the original and modified versions of our model.

  18. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    Energy Technology Data Exchange (ETDEWEB)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G. [Instituto de Astrofísica de La Plata (Argentina); Kuncarayakti, Hanindyo [Millennium Institute of Astrophysics (MAS), Casilla 36-D, Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi, E-mail: gaston@fcaglp.unlp.edu.ar [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan)

    2015-10-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.

  19. Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

    2003-01-01

    The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

  20. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    International Nuclear Information System (INIS)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi

    2015-01-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M ⊙ and the radius was 30–50 R ⊙ , which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion

  1. Luminal progenitors restrict their lineage potential during mammary gland development.

    Science.gov (United States)

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  2. Reporter-Based Isolation of Developmental Myogenic Progenitors

    Directory of Open Access Journals (Sweden)

    Eyemen Kheir

    2018-04-01

    Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.

  3. MIPAS temperature from the stratosphere to the lower thermosphere: Comparison of vM21 with ACE-FTS, MLS, OSIRIS, SABER, SOFIE and lidar measurements

    Directory of Open Access Journals (Sweden)

    M. García-Comas

    2014-11-01

    Full Text Available We present vM21 MIPAS temperatures from the lower stratosphere to the lower thermosphere, which cover all optimized resolution measurements performed by MIPAS in the middle-atmosphere, upper-atmosphere and noctilucent-cloud modes during its lifetime, i.e., from January 2005 to April 2012. The main upgrades with respect to the previous version of MIPAS temperatures (vM11 are the update of the spectroscopic database, the use of a different climatology of atomic oxygen and carbon dioxide, and the improvement in important technical aspects of the retrieval setup (temperature gradient along the line of sight and offset regularizations, apodization accuracy. Additionally, an updated version of ESA-calibrated L1b spectra (5.02/5.06 is used. The vM21 temperatures correct the main systematic errors of the previous version because they provide on average a 1–2 K warmer stratopause and middle mesosphere, and a 6–10 K colder mesopause (except in high-latitude summers and lower thermosphere. These lead to a remarkable improvement in MIPAS comparisons with ACE-FTS, MLS, OSIRIS, SABER, SOFIE and the two Rayleigh lidars at Mauna Loa and Table Mountain, which, with a few specific exceptions, typically exhibit differences smaller than 1 K below 50 km and than 2 K at 50–80 km in spring, autumn and winter at all latitudes, and summer at low to midlatitudes. Differences in the high-latitude summers are typically smaller than 1 K below 50 km, smaller than 2 K at 50–65 km and 5 K at 65–80 km. Differences between MIPAS and the other instruments in the mid-mesosphere are generally negative. MIPAS mesopause is within 4 K of the other instruments measurements, except in the high-latitude summers, when it is within 5–10 K, being warmer there than SABER, MLS and OSIRIS and colder than ACE-FTS and SOFIE. The agreement in the lower thermosphere is typically better than 5 K, except for high latitudes during spring and summer, when MIPAS usually exhibits larger

  4. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    Science.gov (United States)

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  5. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  6. Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

    Science.gov (United States)

    Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

    2015-01-01

    During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

  7. LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf

    2012-01-01

    Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.

  8. Clues on Type Ia Supernovae Progenitors

    International Nuclear Information System (INIS)

    Piersanti, Luciano; Tornambe, Amedeo

    2005-01-01

    We show that in the framework of canonical stellar evolution it is hard, if not impossible, to determine the growth in mass of a CO White Dwarf, up to the Chandrasekhar limit by means of mass transfer from its companion in a binary system. This is the case either if matter is accreted from a normal companion with an H-rich envelope or if direct CO accretion occurs from a CO WD companion. At variance, we show that if the effects of rotation are taken into account in modeling the accretion process, a CO WD can increase its mass at the expenses of the degenerate CO companion up and beyond 1.4 M· , so that an explosive event of the type Ia class is naturally produced. This theoretical finding revives the Double Degenerate scenario for type Ia SNe progenitors. In such a case the internal spread in the observational properties of type Ia SNe may be interpreted as a consequence of different total masses; hence differences between SNe Ia in nearby elliptical galaxies and the majority of those in spirals should be expected and the current use of type Ia SNe as cosmological distance indicators should be justified

  9. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  10. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  11. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  12. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  13. An alternative model to distribute VO software to WLCG sites based on CernVM-FS: a prototype at PIC Tier1

    International Nuclear Information System (INIS)

    Lanciotti, E; Merino, G; Blomer, J; Bria, A

    2011-01-01

    In a distributed computing model as WLCG the software of experiment specific application software has to be efficiently distributed to any site of the Grid. Application software is currently installed in a shared area of the site visible for all Worker Nodes (WNs) of the site through some protocol (NFS, AFS or other). The software is installed at the site by jobs which run on a privileged node of the computing farm where the shared area is mounted in write mode. This model presents several drawbacks which cause a non-negligible rate of job failure. An alternative model for software distribution based on the CERN Virtual Machine File System (CernVM-FS) has been tried at PIC, the Spanish Tierl site of WLCG. The test bed used and the results are presented in this paper.

  14. The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC.

    Science.gov (United States)

    Wang, Weisheng; Ju, Yun-Yue; Zhou, Qi-Xin; Tang, Jian-Xin; Li, Meng; Zhang, Lei; Kang, Shuo; Chen, Zhong-Guo; Wang, Yu-Jun; Ji, Hui; Ding, Yu-Qiang; Xu, Lin; Liu, Jing-Gen

    2017-07-26

    Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA A receptor (GABA A R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA A R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA A R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA A R endocytosis and CPA extinction. The crucial role of GABA A R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA A R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA A R endocytosis. SIGNIFICANCE STATEMENT This study reveals that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories associated with drug withdrawal and identifies Arc as a downstream effector of Rac1 regulations of synaptic plasticity as well as learning and memory, thereby suggesting therapeutic targets to promote extinction of the unwanted memories. Copyright © 2017 the authors 0270-6474/17/377096-15$15.00/0.

  15. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    Science.gov (United States)

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

  16. THE TYPE IIb SUPERNOVA 2011dh FROM A SUPERGIANT PROGENITOR

    International Nuclear Information System (INIS)

    Bersten, Melina C.; Nomoto, Ken'ichi; Folatelli, Gastón; Maeda, Keiichi; Benvenuto, Omar G.; Ergon, Mattias; Sollerman, Jesper; Benetti, Stefano; Ochner, Paolo; Tomasella, Lina; Botticella, Maria Teresa; Fraser, Morgan; Kotak, Rubina

    2012-01-01

    A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star—with R ∼ 200 R ☉ —is needed to reproduce the early light curve (LC) of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the supernova (SN) in deep pre-explosion images is the progenitor star. From the main peak of the bolometric LC and expansion velocities, we constrain the mass of the ejecta to be ≈2 M ☉ , the explosion energy to be E = (6-10) × 10 50 erg, and the 56 Ni mass to be approximately 0.06 M ☉ . The progenitor star was composed of a helium core of 3-4 M ☉ and a thin hydrogen-rich envelope of ≈0.1M ☉ with a main-sequence mass estimated to be in the range of 12-15 M ☉ . Our models rule out progenitors with helium-core masses larger than 8 M ☉ , which correspond to M ZAMS ∼> 25M ☉ . This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.

  17. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

    Science.gov (United States)

    Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

  18. Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

    Science.gov (United States)

    Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

    2012-01-01

    Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  19. Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Petrelli

    2012-01-01

    Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  20. Development and molecular composition of the hepatic progenitor cell niche.

    Science.gov (United States)

    Vestentoft, Peter Siig

    2013-05-01

    End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components

  1. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  2. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    Science.gov (United States)

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  3. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  4. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    Wood-Vasey, William Michael

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of r V = 4.26 -1.93 -0.10 +1.39 +0.10 h 3 x 10 -4 SNe Ia/yr/Mpc 3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  5. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

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  9. Regulation of Mammary Progenitor Cells by p53 and Parity

    Science.gov (United States)

    2011-01-01

    quantitative PCR system (Stratagene). To knockdown Notch1 in TM40A cells, siRNA (s70698 and s70700) were purchased from Ambion. s70698 siRNA sense sequence: 5...hours after transfect ion and real-tim e quantitative P CR was used to confirm the knockdown efficiency. Results Label and chase progenitor cells...cells contained 0.8% o f DsRed positiv e (DsR +) progenitor cells (Fig. 1B). The mammosphere-forming capacity of DsR+ cells is 3.8-fold greater

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  19. File list: His.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: DNS.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  1. File list: Oth.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  2. File list: DNS.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  4. File list: His.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  5. File list: His.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  6. File list: His.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  7. File list: His.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  8. File list: Oth.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  9. File list: DNS.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  10. File list: Pol.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  11. File list: Oth.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  12. File list: Pol.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Pol.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  14. File list: Oth.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: His.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  16. File list: Pol.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: DNS.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Unc.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Unc.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: DNS.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  2. File list: His.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Unc.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  4. File list: Unc.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  5. File list: Unc.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Unc.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  7. File list: Pol.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  8. File list: His.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Pol.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Oth.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  14. File list: Unc.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  15. File list: Unc.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  16. File list: His.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  19. File list: Pol.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  20. File list: His.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  1. File list: Unc.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: DNS.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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    Full Text Available DNS.Neu.05.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  3. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  4. Cellular therapy after spinal cord injury using neural progenitor cells

    NARCIS (Netherlands)

    Vroemen, Maurice

    2006-01-01

    In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic

  5. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  6. Long GRBs from binary stars: runaway, Wolf-Rayet progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution — the latter had previously

  7. Long GRBs from Binary Stars: Runaway, Wolf-Rayet Progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution - the latter had previously

  8. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory m...

  9. Intersections of lung progenitor cells, lung disease and lung cancer.

    Science.gov (United States)

    Kim, Carla F

    2017-06-30

    The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

  10. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  11. Mobilization of hematopoietic stem and progenitor cells in mice

    NARCIS (Netherlands)

    Robinson, Simon N; van Os, Ronald P; Bunting, Kevin

    2008-01-01

    Animal models have added significantly to our understanding of the mechanism(s) of hematopoietic stem and progenitor cell (HSPC) mobilization. Such models suggest that changes in the interaction between the HSPC and the hematopoietic microenvironmental 'niche' (cellular and extracellular components)

  12. Endothelial progenitor cell-based neovascularization : implications for therapy

    NARCIS (Netherlands)

    Krenning, Guido; van Luyn, Marja J. A.; Harmsen, Martin C.

    Ischemic cardiovascular events are a major cause of death globally. Endothelial progenitor cell (EPC)-based approaches can result in improvement of vascular perfusion and might offer clinical benefit. However, although functional improvement is observed, the lack of long-term engraftment of EPCs

  13. The progenitor of Nova Cygni 2006 (=V2362 Cyg)

    NARCIS (Netherlands)

    Steeghs, D.; Greimel, R.; Drew, J.; Irwin, M.; Gaensicke, B.; Groot, P.J.; Knigge, C.

    2006-01-01

    We report on the detection of the likely progenitor to Nova Cygni 2006 = V2362 Cyg (IAUC #8697, #8698, ATel #792) using images from the INT Photometric H-Alpha Survey (IPHAS; http://www.iphas.org). The field containing the classical nova was observed as part of our galactic plane survey on Aug. 3rd

  14. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry

    2006-01-01

    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin...

  15. Mass ejection in failed supernovae: variation with stellar progenitor

    Science.gov (United States)

    Fernández, Rodrigo; Quataert, Eliot; Kashiyama, Kazumi; Coughlin, Eric R.

    2018-05-01

    We study the ejection of mass during stellar core-collapse when the stalled shock does not revive and a black hole forms. Neutrino emission during the protoneutron star phase causes a decrease in the gravitational mass of the core, resulting in an outward going sound pulse that steepens into a shock as it travels out through the star. We explore the properties of this mass ejection mechanism over a range of stellar progenitors using spherically symmetric, time-dependent hydrodynamic simulations that treat neutrino mass-loss parametrically and follow the shock propagation over the entire star. We find that all types of stellar progenitor can eject mass through this mechanism. The ejected mass is a decreasing function of the surface gravity of the star, ranging from several M⊙ for red supergiants to ˜0.1 M⊙ for blue supergiants and ˜10-3 M⊙ for Wolf-Rayet stars. We find that the final shock energy at the surface is a decreasing function of the core-compactness, and is ≲ 1047-1048 erg in all cases. In progenitors with a sufficiently large envelope, high core-compactness, or a combination of both, the sound pulse fails to unbind mass. Successful mass ejection is accompanied by significant fallback accretion that can last from hours to years. We predict the properties of shock breakout and thermal plateau emission produced by the ejection of the outer envelope of blue supergiant and Wolf-Rayet progenitors in otherwise failed supernovae.

  16. Hmga2 regulates self-renewal of retinal progenitors.

    Science.gov (United States)

    Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

    2014-11-01

    In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

  17. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  18. Characteristics of meniscus progenitor cells migrated from injured meniscus.

    Science.gov (United States)

    Seol, Dongrim; Zhou, Cheng; Brouillette, Marc J; Song, Ino; Yu, Yin; Choe, Hyeong Hun; Lehman, Abigail D; Jang, Kee W; Fredericks, Douglas C; Laughlin, Barbara J; Martin, James A

    2017-09-01

    Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy. We showed previously that migratory chondrogenic progenitor cells (CPCs) were recruited to injured cartilage, where they showed a capability in situ tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells. Explant studies revealed that migrating cells were mainly confined to the red zone in normal menisci: However, these cells were capable of repopulating defects made in the white zone. In vivo, migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. Gene expression profiling showed that the migrating population was more similar to CPCs than other meniscus cells. Finally, migrating cells equaled CPCs in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1966-1972, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. TYPE IIb SUPERNOVAE WITH COMPACT AND EXTENDED PROGENITORS

    International Nuclear Information System (INIS)

    Chevalier, Roger A.; Soderberg, Alicia M.

    2010-01-01

    The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius ∼1 x 10 11 cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is ∼0.1 M sun .

  20. Cardiac stem/progenitor cells, secreted proteins, and proteomics

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Abraham, M.R.; Van Eyk, J.E.

    2009-01-01

    Roč. 583, č. 11 (2009), s. 1800-1807 ISSN 0014-5793 Institutional research plan: CEZ:AV0Z40310501 Keywords : Cardiac stem/progenitor cell * paracrine factor * secretome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.541, year: 2009

  1. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jing Song

    2018-03-01

    Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  2. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.

    Science.gov (United States)

    Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang

    2018-03-22

    A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  3. [Stem and progenitor cells in biostructure of blood vessel walls].

    Science.gov (United States)

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  4. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  5. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  6. The Antarctica component of postglacial rebound model ICE-6G_C (VM5a) based on GPS positioning, exposure age dating of ice thicknesses, and relative sea level histories

    Science.gov (United States)

    Argus, Donald F.; Peltier, W. R.; Drummond, R.; Moore, Angelyn W.

    2014-07-01

    A new model of the deglaciation history of Antarctica over the past 25 kyr has been developed, which we refer to herein as ICE-6G_C (VM5a). This revision of its predecessor ICE-5G (VM2) has been constrained to fit all available geological and geodetic observations, consisting of: (1) the present day uplift rates at 42 sites estimated from GPS measurements, (2) ice thickness change at 62 locations estimated from exposure-age dating, (3) Holocene relative sea level histories from 12 locations estimated on the basis of radiocarbon dating and (4) age of the onset of marine sedimentation at nine locations along the Antarctic shelf also estimated on the basis of 14C dating. Our new model fits the totality of these data well. An additional nine GPS-determined site velocities are also estimated for locations known to be influenced by modern ice loss from the Pine Island Bay and Northern Antarctic Peninsula regions. At the 42 locations not influenced by modern ice loss, the quality of the fit of postglacial rebound model ICE-6G_C (VM5A) is characterized by a weighted root mean square residual of 0.9 mm yr-1. The Southern Antarctic Peninsula is inferred to be rising at 2 mm yr-1, requiring there to be less Holocene ice loss there than in the prior model ICE-5G (VM2). The East Antarctica coast is rising at approximately 1 mm yr-1, requiring ice loss from this region to have been small since Last Glacial Maximum. The Ellsworth Mountains, at the base of the Antarctic Peninsula, are inferred to be rising at 5-8 mm yr-1, indicating large ice loss from this area during deglaciation that is poorly sampled by geological data. Horizontal deformation of the Antarctic Plate is minor with two exceptions. First, O'Higgins, at the tip of the Antarctic Peninsula, is moving southeast at a significant 2 mm yr-1 relative to the Antarctic Plate. Secondly, the margins of the Ronne and Ross Ice Shelves are moving horizontally away from the shelf centres at an approximate rate of 0.8 mm yr-1, in

  7. PROGENITOR-EXPLOSION CONNECTION AND REMNANT BIRTH MASSES FOR NEUTRINO-DRIVEN SUPERNOVAE OF IRON-CORE PROGENITORS

    Energy Technology Data Exchange (ETDEWEB)

    Ugliano, Marcella; Janka, Hans-Thomas; Marek, Andreas [Max-Planck-Institut fuer Astrophysik, Karl-Schwarzschild-Str. 1, D-85748 Garching (Germany); Arcones, Almudena [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 2, D-64289 Darmstadt (Germany)

    2012-09-20

    We perform hydrodynamic supernova (SN) simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 M{sub Sun} are compatible with SN 1987A. Thus, we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit large variability even in narrow intervals of the progenitors' zero-age main-sequence mass. While all progenitors with masses below {approx}15 M{sub Sun} yield NSs, black hole (BH) as well as NS formation is possible for more massive stars, where partial loss of the hydrogen envelope leads to weak reverse shocks and weak fallback. Our NS baryonic masses of {approx}1.2-2.0 M{sub Sun} and BH masses >6 M{sub Sun} are compatible with a possible lack of low-mass BHs in the empirical distribution. Neutrino heating accounts for SN energies between some 10{sup 50} erg and {approx}2 Multiplication-Sign 10{sup 51} erg but can hardly explain more energetic explosions and nickel masses higher than 0.1-0.2 M{sub Sun }. These seem to require an alternative SN mechanism.

  8. TIG- en plasmalassen : VM 81

    NARCIS (Netherlands)

    W.G. Essers

    2010-01-01

    Voor u ligt de voorlichtingspublicatie "TIG- en plasmalassen". Deze voorlichtingspublicatie is bedoeld voor allen die te maken hebben of te maken krijgen met toepassing van de betreffende verbindingstechnieken. Daarbij moet worden gedacht aan bijvoorbeeld constructeurs,

  9. Glacial Isostatic Adjustment Derived Boundary Conditions for Paleoclimate Simulation: the Refined ICE-6G_D (VM5a) Model and the Dansgaard-Oeschger Oscillation

    Science.gov (United States)

    Peltier, W. R.; Vettoretti, G.; Argus, D. F.

    2017-12-01

    Global models of the glacial isostatic adjustment (GIA) process are designed to fit a wide range of geophysical and geomorphological observations that simultaneously constrain the internal viscoelastic structure of Earths interior and the history of grounded ice thickness variations that has occurred over the most recent ice-age cycle of the Late Quaternary interval of time. The most recent refinement of the ICE-NG (VMX) series of such global models from the University of Toronto, ICE-6G_C (VM5a), has recently been slightly modified insofar as its Antarctic component is concerned to produce a "_D" version of the structure. This has been chosen to provide the boundary conditions for the next round of model-data inter-comparisons in the context of the international Paleoclimate Modeling Inter-comparison Project (PMIP). The output of PMIP will contribute to the Sixth Assessment Report (AR6) of the Intergovernmental Panel on Climate Change which is now under way. A highly significant test of the utility of this latest model has recently been performed that is focused upon the Dansgaard-Oeschger oscillation that was the primary source of climate variability during Marine Isotope Stage 3 (MIS3) of the most recent glacial cycle. By introducing the surface boundary conditions for paleotopography and paleobathymetry, land-sea mask and surface albedo into the NCAR CESM1 coupled climate model configured at full one degree by one degree CMIP5 resolution, together with the appropriate trace gas and orbital insolation forcing, we show that the millennium timescale Dansgard-Oeschger oscillation naturally develops following spin- up of the model into the glacial state.

  10. Single progenitor model for GW150914 and GW170104

    Science.gov (United States)

    D'Orazio, Daniel J.; Loeb, Abraham

    2018-04-01

    The merger of stellar-mass black holes (BHs) is not expected to generate detectable electromagnetic (EM) emission. However, the gravitational wave (GW) events GW150914 and GW170104, detected by the Laser Interferometer Gravitational Wave Observatory to be the result of merging, ˜60 M⊙ binary black holes (BBHs), each have claimed coincident gamma-ray emission. Motivated by the intriguing possibility of an EM counterpart to BBH mergers, we construct a model that can reproduce the observed EM and GW signals for GW150914- and GW170104-like events, from a single-star progenitor. Following Loeb [Astrophys. J. Lett. 819, L21 (2016), 10.3847/2041-8205/819/2/L21], we envision a massive, rapidly rotating star within which a rotating-bar instability fractures the core into two overdensities that fragment into clumps which merge to form BHs in a tight binary with arbitrary spin-orbit alignment. Once formed, the BBH inspirals due to gas and gravitational-wave drag until tidal forces trigger strong feeding of the BHs with the surrounding stellar-density gas about 10 sec before merger. The resulting giga-Eddington accretion peak launches a jet that breaks out of the progenitor star and drives a powerful outflow that clears the gas from the orbit of the binary within 1 sec, preserving the vacuum GW waveform in the Laser Interferometer Gravitational Wave Observatory band. The single-progenitor scenario predicts the existence of variability of the gamma-ray burst, modulated at the ˜0.2 sec chirping period of the BBH due to relativistic Doppler boost. The jet breakout should be accompanied by a low-luminosity supernova. Finally, because the BBHs of the single-progenitor model do not exist at large separations, they will not be detectable in the low-frequency gravitational-wave band of the Laser Interferometer Space Antenna. Hence, the single-progenitor BBHs will be unambiguously discernible from BBHs formed through alternate, double-progenitor evolution scenarios.

  11. State-dependent compound inhibition of Nav1.2 sodium channels using the FLIPR Vm dye: on-target and off-target effects of diverse pharmacological agents.

    Science.gov (United States)

    Benjamin, Elfrida R; Pruthi, Farhana; Olanrewaju, Shakira; Ilyin, Victor I; Crumley, Gregg; Kutlina, Elena; Valenzano, Kenneth J; Woodward, Richard M

    2006-02-01

    Voltage-gated sodium channels (NaChs) are relevant targets for pain, epilepsy, and a variety of neurological and cardiac disorders. Traditionally, it has been difficult to develop structure-activity relationships for NaCh inhibitors due to rapid channel kinetics and state-dependent compound interactions. Membrane potential (Vm) dyes in conjunction with a high-throughput fluorescence imaging plate reader (FLIPR) offer a satisfactory 1st-tier solution. Thus, the authors have developed a FLIPR Vm assay of rat Nav1.2 NaCh. Channels were opened by addition of veratridine, and Vm dye responses were measured. The IC50 values from various structural classes of compounds were compared to the resting state binding constant (Kr)and inactivated state binding constant (Ki)obtained using patch-clamp electrophysiology (EP). The FLIPR values correlated with Ki but not Kr. FLIPRIC50 values fell within 0.1-to 1.5-fold of EP Ki values, indicating that the assay generally reports use-dependent inhibition rather than resting state block. The Library of Pharmacologically Active Compounds (LOPAC, Sigma) was screened. Confirmed hits arose from diverse classes such as dopamine receptor antagonists, serotonin transport inhibitors, and kinase inhibitors. These data suggest that NaCh inhibition is inherent in a diverse set of biologically active molecules and may warrant counterscreening NaChs to avoid unwanted secondary pharmacology.

  12. La violencia de hijos adolescentes contra sus progenitores La violencia de hijos adolescentes contra sus progenitores

    Directory of Open Access Journals (Sweden)

    Concepción Aroca Montolío

    2013-10-01

    Full Text Available According to Prosecutor’s Office of the Minor, the accusation interposed by mothers and/or fathers victims by theirs children, along 2007 were 2603, in 2008 amounted 4.211, in 2009 there were 5.209 and in 2010 there were 8.000 accusations. Suede this worrying increase, the principal aim of our article is to check the scientific international and national documentation, from 1957 until the year 2010 that analyses the phenomenon of the adolescent violence against parents, to achieve an approximation to its keys that there allows us the comprehension and analysis of this serious familiar problem. For it we will analyse: (a the importance of this crime by means of criminological mediators: prevalence and incidence; (b the age and sex variables’ aggressors to be able to establish a basic profile about theirs and, (c the violence types that the teenagers wield to damage, prejudice and suffering against their progenitors, with the aim to obtain what they want. The information obtained in this research review and qualitative analysis, change in base to the methodology used and the type of sample under study to obtain conclusions. Even though, we wantto do research into needs to investigate this type of familiar violence, and from there, to do researches with rigorous scientific methodologies, unifying criteria and variables to be investigating, to be able to anticipate in this increasing problem that the parents have. Según la Fiscalía del Menor en el año 2007, las denuncias interpuestas por madres y/o padres, víctimas de malos tratos por sus hijos e hijas menores de edad, fueron 2.683. En 2008 ascendieron a 4.211, en 2009 se presentaron 5.209 y en el año 2010 se registraron 8.000 denuncias. Ante éste preocupante incremento, el objetivo principal de nuestro artículo es revisar la documentación científica que analiza la violencia filio-parental,  desde 1957 hasta el año 2011, para lograr una aproximación a sus claves que nos permita la

  13. Progenitors of type Ia supernovae in elliptical galaxies

    International Nuclear Information System (INIS)

    Gilfanov, M.; Bogdan, A.

    2011-01-01

    Although there is a nearly universal agreement that type Ia supernovae are associated with the thermonuclear disruption of a CO white dwarf, the exact nature of their progenitors is still unknown. The single degenerate scenario envisages a white dwarf accreting matter from a non-degenerate companion in a binary system. Nuclear energy of the accreted matter is released in the form of electromagnetic radiation or gives rise to numerous classical nova explosions prior to the supernova event. We show that combined X-ray output of supernova progenitors and statistics of classical novae predicted in the single degenerate scenario are inconsistent with X-ray and optical observations of nearby early type galaxies and galaxy bulges. White dwarfs accreting from a donor star in a binary system and detonating at the Chandrasekhar mass limit can account for no more than ∼5% of type Ia supernovae observed in old stellar populations.

  14. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  15. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osório, M. Joana; Goldman, Steven A.

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  16. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  17. Is black-hole ringdown a memory of its progenitor?

    Science.gov (United States)

    Kamaretsos, Ioannis; Hannam, Mark; Sathyaprakash, B S

    2012-10-05

    We perform an extensive numerical study of coalescing black-hole binaries to understand the gravitational-wave spectrum of quasinormal modes excited in the merged black hole. Remarkably, we find that the masses and spins of the progenitor are clearly encoded in the mode spectrum of the ringdown signal. Some of the mode amplitudes carry the signature of the binary's mass ratio, while others depend critically on the spins. Simulations of precessing binaries suggest that our results carry over to generic systems. Using Bayesian inference, we demonstrate that it is possible to accurately measure the mass ratio and a proper combination of spins even when the binary is itself invisible to a detector. Using a mapping of the binary masses and spins to the final black-hole spin allows us to further extract the spin components of the progenitor. Our results could have tremendous implications for gravitational astronomy by facilitating novel tests of general relativity using merging black holes.

  18. THE POPULATION OF HELIUM-MERGER PROGENITORS: OBSERVATIONAL PREDICTIONS

    International Nuclear Information System (INIS)

    Fryer, Chris L.; Belczynski, Krzysztof; Bulik, Tomasz; Berger, Edo; Thöne, Christina; Ellinger, Carola

    2013-01-01

    The helium-merger gamma-ray burst (GRB) progenitor is produced by the rapid accretion onto a compact remnant (neutron star or black hole) when it undergoes a common envelope inspiral with its companion's helium core. This merger phase produces a very distinct environment around these outbursts and recent observations suggest that, in some cases, we are detecting the signatures of the past merger in the GRB afterglow. These observations allow us, for the first time, to study the specific features of the helium-merger progenitor. In this paper, we couple population synthesis calculations to our current understanding of GRB engines and common envelope evolution to make observational predictions for the helium-merger GRB population. Many mergers do not produce GRB outbursts and we discuss the implications of these mergers with the broader population of astrophysical transients.

  19. Progenitor cell populations in the periodontal ligament of mice

    International Nuclear Information System (INIS)

    McCulloch, C.A.

    1985-01-01

    Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3 H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

  20. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess...

  1. The Progenitor Dependence of Core-collapse Supernovae from Three-dimensional Simulations with Progenitor Models of 12–40 M ⊙

    Science.gov (United States)

    Ott, Christian D.; Roberts, Luke F.; da Silva Schneider, André; Fedrow, Joseph M.; Haas, Roland; Schnetter, Erik

    2018-03-01

    We present a first study of the progenitor star dependence of the three-dimensional (3D) neutrino mechanism of core-collapse supernovae. We employ full 3D general-relativistic multi-group neutrino radiation-hydrodynamics and simulate the postbounce evolutions of progenitors with zero-age main sequence masses of 12, 15, 20, 27, and 40 M ⊙. All progenitors, with the exception of the 12 M ⊙ star, experience shock runaway by the end of their simulations. In most cases, a strongly asymmetric explosion will result. We find three qualitatively distinct evolutions that suggest a complex dependence of explosion dynamics on progenitor density structure, neutrino heating, and 3D flow. (1) Progenitors with massive cores, shallow density profiles, and high post-core-bounce accretion rates experience very strong neutrino heating and neutrino-driven turbulent convection, leading to early shock runaway. Accretion continues at a high rate, likely leading to black hole formation. (2) Intermediate progenitors experience neutrino-driven, turbulence-aided explosions triggered by the arrival of density discontinuities at the shock. These occur typically at the silicon/silicon–oxygen shell boundary. (3) Progenitors with small cores and density profiles without strong discontinuities experience shock recession and develop the 3D standing-accretion shock instability (SASI). Shock runaway ensues late, once declining accretion rate, SASI, and neutrino-driven convection create favorable conditions. These differences in explosion times and dynamics result in a non-monotonic relationship between progenitor and compact remnant mass.

  2. Efficacy and Safety of Human Retinal Progenitor Cells

    Science.gov (United States)

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  3. Constraints on the Progenitor System of SN 2016gkg from a Comprehensive Statistical Analysis

    Science.gov (United States)

    Sravan, Niharika; Marchant, Pablo; Kalogera, Vassiliki; Margutti, Raffaella

    2018-01-01

    Type IIb supernovae (SNe) present a unique opportunity for understanding the progenitors of stripped-envelope SNe because the stellar progenitor of several SNe IIb have been identified in pre-explosion images. In this paper, we use Bayesian inference and a large grid of non-rotating solar-metallicity single and binary stellar models to derive the associated probability distributions of single and binary progenitors of the SN IIb 2016gkg using existing observational constraints. We find that potential binary star progenitors have smaller pre-SN hydrogen-envelope and helium-core masses than potential single-star progenitors typically by 0.1 M ⊙ and 2 M ⊙, respectively. We find that, a binary companion, if present, is a main-sequence or red-giant star. Apart from this, we do not find strong constraints on the nature of the companion star. We demonstrate that the range of progenitor helium-core mass inferred from observations could help improve constraints on the progenitor. We find that the probability that the progenitor of SN 2016gkg was a binary is 22% when we use constraints only on the progenitor luminosity and effective temperature. Imposing the range of pre-SN progenitor hydrogen-envelope mass and radius inferred from SN light curves, the probability that the progenitor is a binary increases to 44%. However, there is no clear preference for a binary progenitor. This is in contrast to binaries being the currently favored formation channel for SNe IIb. Our analysis demonstrates the importance of statistical inference methods to constrain progenitor channels.

  4. Endothelial Progenitor Cells as Shuttle of Anticancer Agents.

    Science.gov (United States)

    Laurenzana, Anna; Margheri, Francesca; Chillà, Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario

    2016-10-01

    Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining cell-based therapy with gene therapy or with nanomedicine. The first approach is based on the possibility of engineering EPCs to express different transgenes, and the second is based on the capacity of EPCs to take up nanomaterials. Here we review the most important progress covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularization and metastasis, and preclinical data about their use in cell-based tumor therapy, considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in terms of plasmonic-dependent thermoablation and molecular imaging.

  5. NEUTRONIZATION DURING CARBON SIMMERING IN TYPE IA SUPERNOVA PROGENITORS

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rodríguez, Héctor; Badenes, Carles [Department of Physics and Astronomy and Pittsburgh Particle Physics, Astrophysics and Cosmology Center (PITT PACC), University of Pittsburgh, 3941 O’Hara Street, Pittsburgh, PA 15260 (United States); Piro, Anthony L. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Schwab, Josiah, E-mail: hector.mr@pitt.edu [Department of Physics, University of California, Berkeley, CA 94720 (United States)

    2016-07-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ∼10{sup 3}–10{sup 4} years of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the MESA stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ≈ 3 × 10{sup −4}. This is ≈ 70% lower than that found in previous studies that do not take the full density and temperature profile of the simmering region into account. Our results imply that the progenitor metallicity is the main contributor to the neutron excess in SN Ia fuel for Z ≳ 1/3 Z {sub ⊙}. Alternatively, at lower metallicities, this neutron excess provides a floor that should be present in any centrally-ignited SN Ia scenario.

  6. Epigenome profiling and editing of neocortical progenitor cells during development.

    Science.gov (United States)

    Albert, Mareike; Kalebic, Nereo; Florio, Marta; Lakshmanaperumal, Naharajan; Haffner, Christiane; Brandl, Holger; Henry, Ian; Huttner, Wieland B

    2017-09-01

    The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo , which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development. © 2017 The Authors.

  7. Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells

    International Nuclear Information System (INIS)

    Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Johnson, Deadre J.

    2009-01-01

    There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

  8. Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors

    Directory of Open Access Journals (Sweden)

    Julie Helft

    2017-07-01

    Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.

  9. Towards the therapeutic use of vascular smooth muscle progenitor cells.

    Science.gov (United States)

    Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

    2012-07-15

    Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

  10. NEUTRONIZATION DURING CARBON SIMMERING IN TYPE IA SUPERNOVA PROGENITORS

    International Nuclear Information System (INIS)

    Martínez-Rodríguez, Héctor; Badenes, Carles; Piro, Anthony L.; Schwab, Josiah

    2016-01-01

    When a Type Ia supernova (SN Ia) progenitor first ignites carbon in its core, it undergoes ∼10 3 –10 4 years of convective burning prior to the onset of thermonuclear runaway. This carbon simmering phase is important for setting the thermal profile and composition of the white dwarf. Using the MESA stellar evolution code, we follow this convective burning and examine the production of neutron-rich isotopes. The neutron content of the SN fuel has important consequences for the ensuing nucleosynthesis, and in particular, for the production of secondary Fe-peak nuclei like Mn and stable Ni. These elements have been observed in the X-ray spectra of SN remnants like Tycho, Kepler, and 3C 397, and their yields can provide valuable insights into the physics of SNe Ia and the properties of their progenitors. We find that weak reactions during simmering can at most generate a neutron excess of ≈ 3 × 10 −4 . This is ≈ 70% lower than that found in previous studies that do not take the full density and temperature profile of the simmering region into account. Our results imply that the progenitor metallicity is the main contributor to the neutron excess in SN Ia fuel for Z ≳ 1/3 Z ⊙ . Alternatively, at lower metallicities, this neutron excess provides a floor that should be present in any centrally-ignited SN Ia scenario.

  11. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Caterina Oriana Aragona

    2016-01-01

    Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

  12. Requirement of mouse BCCIP for neural development and progenitor proliferation.

    Directory of Open Access Journals (Sweden)

    Yi-Yuan Huang

    Full Text Available Multiple DNA repair pathways are involved in the orderly development of neural systems at distinct stages. The homologous recombination (HR pathway is required to resolve stalled replication forks and critical for the proliferation of progenitor cells during neural development. BCCIP is a BRCA2 and CDKN1A interacting protein implicated in HR and inhibition of DNA replication stress. In this study, we determined the role of BCCIP in neural development using a conditional BCCIP knock-down mouse model. BCCIP deficiency impaired embryonic and postnatal neural development, causing severe ataxia, cerebral and cerebellar defects, and microcephaly. These development defects are associated with spontaneous DNA damage and subsequent cell death in the proliferative cell populations of the neural system during embryogenesis. With in vitro neural spheroid cultures, BCCIP deficiency impaired neural progenitor's self-renewal capability, and spontaneously activated p53. These data suggest that BCCIP and its anti-replication stress functions are essential for normal neural development by maintaining an orderly proliferation of neural progenitors.

  13. Observational properties of SNe Ia progenitors close to the explosion

    Science.gov (United States)

    Tornambé, A.; Piersanti, L.; Raimondo, G.; Delgrande, R.

    2018-04-01

    We determine the expected signal in various observational bands of supernovae Ia progenitors just before the explosion by assuming the rotating double-degenerate scenario. Our results are valid also for all the evolutionary scenarios invoking rotation as the driving mechanism of the accretion process as well as the evolution up to the explosion. We find that the observational properties depend mainly on the mass of the exploding object, even if the angular momentum evolution after the end of the mass accretion phase and before the onset of C-burning plays a non-negligible role. Just before the explosion, the magnitude MV ranges between 9 and 11 mag, while the colour (F225W - F555W) is about -1.64 mag. The photometric properties remain constant for a few decades before the explosion. During the last few months, the luminosity decreases very rapidly. The corresponding decline in the optical bands varies from a few hundredths up to one magnitude, the exact value depending on both the white dwarf total mass and the braking efficiency at the end of the mass transfer. This feature is related to the exponentially increasing energy production, which drives the formation of a convective core rapidly extending over a large part of the exploding object. Also, a drop in the angular velocity occurs. We find that observations in the soft X band (0.5-2 keV) may be used to check if the evolution of the SNe Ia progenitors up to the explosion is driven by rotation and, hence, to discriminate among different progenitor scenarios.

  14. Enrichment of rat oligodendrocyte progenitor cells by magnetic cell sorting

    Czech Academy of Sciences Publication Activity Database

    Čížková, D.; Čížek, M.; Nagyová, M.; Slovinská, L.; Novotná, I.; Jergová, S.; Radoňák, J.; Hlučilová, Jana; Vanický, I.

    2009-01-01

    Roč. 184, č. 1 (2009), s. 88-94 ISSN 0165-0270 R&D Projects: GA MŠk MEB0808108 Grant - others:Agentúra na podporu výskumu a vývoja(SK) APVV-51002105; Agentúra na podporu výskumu a vývoja(SK) APVV SK-CZ-0045-07 Institutional research plan: CEZ:AV0Z50450515 Keywords : Oligodendrocytes progenitors Lineage * Magnetic separation Subject RIV: FH - Neurology Impact factor: 2.295, year: 2009

  15. Germinación, microinjertación y cultivo de callos in vitro de Vasconcellea stipulata V.M. Badillo y Vasconcellea pubescens A.DC

    OpenAIRE

    Espinosa Soto, Isabel

    2016-01-01

    En varias poblaciones rurales de regiones andinas y centroamericanas se utilizan con fines etnomédicos las hojas, el látex y el fruto de las plantas de la familia Caricaceae cuyo miembro más representativo es la papaya (Carica papaya L.), la cual produce la fuente comercial más importante de la enzima proteolítica papaína. El presente trabajo estudia las especies Vasconcellea stipulata V.M. Badillo y Vasconcellea pubescens A.DC que pertenecen al género Vasconcellea, miembros de la familia Car...

  16. Inter-progenitor pool wiring: An evolutionarily conserved strategy that expands neural circuit diversity.

    Science.gov (United States)

    Suzuki, Takumi; Sato, Makoto

    2017-11-15

    Diversification of neuronal types is key to establishing functional variations in neural circuits. The first critical step to generate neuronal diversity is to organize the compartmental domains of developing brains into spatially distinct neural progenitor pools. Neural progenitors in each pool then generate a unique set of diverse neurons through specific spatiotemporal specification processes. In this review article, we focus on an additional mechanism, 'inter-progenitor pool wiring', that further expands the diversity of neural circuits. After diverse types of neurons are generated in one progenitor pool, a fraction of these neurons start migrating toward a remote brain region containing neurons that originate from another progenitor pool. Finally, neurons of different origins are intermingled and eventually form complex but precise neural circuits. The developing cerebral cortex of mammalian brains is one of the best examples of inter-progenitor pool wiring. However, Drosophila visual system development has revealed similar mechanisms in invertebrate brains, suggesting that inter-progenitor pool wiring is an evolutionarily conserved strategy that expands neural circuit diversity. Here, we will discuss how inter-progenitor pool wiring is accomplished in mammalian and fly brain systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Selective In Vitro Propagation of Nephron Progenitors Derived from Embryos and Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Shunsuke Tanigawa

    2016-04-01

    Full Text Available Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, in mice, the progenitors terminally differentiate shortly after birth. Here, we report a method for selectively expanding nephron progenitors in vitro in an undifferentiated state. Combinatorial and concentration-dependent stimulation with LIF, FGF2/9, BMP7, and a WNT agonist is critical for expansion. The purified progenitors proliferated beyond the physiological limits observed in vivo, both for cell numbers and lifespan. Neonatal progenitors were maintained for a week, while progenitors from embryonic day 11.5 expanded 1,800-fold for nearly 20 days and still reconstituted 3D nephrons containing glomeruli and renal tubules. Furthermore, progenitors generated from mouse embryonic stem cells and human induced pluripotent cells could be expanded with retained nephron-forming potential. Thus, we have established in vitro conditions for promoting the propagation of nephron progenitors, which will be essential for dissecting the mechanisms of kidney organogenesis and for regenerative medicine.

  18. Selective In Vitro Propagation of Nephron Progenitors Derived from Embryos and Pluripotent Stem Cells.

    Science.gov (United States)

    Tanigawa, Shunsuke; Taguchi, Atsuhiro; Sharma, Nirmala; Perantoni, Alan O; Nishinakamura, Ryuichi

    2016-04-26

    Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, in mice, the progenitors terminally differentiate shortly after birth. Here, we report a method for selectively expanding nephron progenitors in vitro in an undifferentiated state. Combinatorial and concentration-dependent stimulation with LIF, FGF2/9, BMP7, and a WNT agonist is critical for expansion. The purified progenitors proliferated beyond the physiological limits observed in vivo, both for cell numbers and lifespan. Neonatal progenitors were maintained for a week, while progenitors from embryonic day 11.5 expanded 1,800-fold for nearly 20 days and still reconstituted 3D nephrons containing glomeruli and renal tubules. Furthermore, progenitors generated from mouse embryonic stem cells and human induced pluripotent cells could be expanded with retained nephron-forming potential. Thus, we have established in vitro conditions for promoting the propagation of nephron progenitors, which will be essential for dissecting the mechanisms of kidney organogenesis and for regenerative medicine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Progress of stem/progenitor cell-based therapy for retinal degeneration.

    Science.gov (United States)

    Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping

    2017-05-10

    Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

  20. Proof of region-specific multipotent progenitors in human breast epithelia

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J; Villadsen, René; Morsing, Mikkel

    2017-01-01

    in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify...

  1. Effects of hematopoietic growth factors on purified bone marrow progenitor cells

    NARCIS (Netherlands)

    F.J. Bot (Freek)

    1992-01-01

    textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3

  2. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  3. Direct observation of hematopoietic progenitor chimerism in fetal freemartin cattle

    Directory of Open Access Journals (Sweden)

    Taponen Juhani

    2007-11-01

    Full Text Available Abstract Background Cattle twins are well known as blood chimeras. However, chimerism in the actual hematopoietic progenitor compartment has not been directly investigated. Here, we analyzed fetal liver of chimeric freemartin cattle by combining a new anti-bovine CD34 antibody and Y-chromosome specific in situ hybridization. Results Bull-derived CD34+ cells were detected in the liver of the female sibling (freemartin at 60 days gestation. The level of bull-derived CD34+ cells was lower in the freemartin than in its male siblings. Bull (Y+ and cow hematopoietic cells often occurred in separate clusters. Around clusters of Y+CD34+ cells, Y+CD34- cells were typically observed. The thymi were also strongly chimeric at 60 days of gestation. Conclusion The fetal freemartin liver contains clusters of bull-derived hematopoietic progenitors, suggesting clonal expansion and differentiation. Even the roots of the hematopoietic system in cattle twins are thus strongly chimeric from the early stages of fetal development. However, the hematopoietic seeding of fetal liver apparently started already before the onset of functional vascular anastomosis.

  4. Selection of progenitors for increase in oil content in soybean

    Directory of Open Access Journals (Sweden)

    Josiane Isabela da Silva Rodrigues

    Full Text Available ABSTRACT The low genetic diversity brings limitation to breeding, because genetically similar genotypes share alleles in common, causing little complementarity and low vigor due to the low levels of heterozygosity in crosses. The objective of this work was to analyze the oil content and genetic diversity of soybean genotypes (Glycine max (L. Merrill based on QTL regions of this trait for choice of progenitors for increase in oil content. Twenty-two genotypes with wide variation in oil content, including cultivars with high oil contents, were cultivated in different Brazilian conditions and the oil content of the grains was quantified by infrared spectrometry. Microsatellite markers selected based on QTL regions for oil content in soybean were analyzed to estimate the genetic diversity. In these studies, a wide variation in oil content (17.28-23.01% and a reasonable diversity among the genotypes were observed, being PI181544 the most divergent genotype, followed by Suprema. The genotypes PI371610/Suprema and Suprema/CD01RR8384 showed genetic distance and higher oil contents in the grains, while the cultivars Suprema and CD01RR8384 had the highest oil contents and proved to be little genetically related. These genotypes are promising progenitors for selection of high oil content in soybean.

  5. Metallicity gradient of the thick disc progenitor at high redshift

    Science.gov (United States)

    Kawata, Daisuke; Allende Prieto, Carlos; Brook, Chris B.; Casagrande, Luca; Ciucă, Ioana; Gibson, Brad K.; Grand, Robert J. J.; Hayden, Michael R.; Hunt, Jason A. S.

    2018-01-01

    We have developed a novel Markov Chain Monte Carlo chemical 'painting' technique to explore possible radial and vertical metallicity gradients for the thick disc progenitor. In our analysis, we match an N-body simulation to the data from the Apache Point Observatory Galactic Evolution Experiment survey. We assume that the thick disc has a constant scaleheight and has completed its formation at an early epoch, after which time radial mixing of its stars has taken place. Under these assumptions, we find that the initial radial metallicity gradient of the thick disc progenitor should not be negative, but either flat or even positive, to explain the current negative vertical metallicity gradient of the thick disc. Our study suggests that the thick disc was built-up in an inside-out and upside-down fashion, and older, smaller and thicker populations are more metal poor. In this case, star-forming discs at different epochs of the thick disc formation are allowed to have different radial metallicity gradients, including a negative one, which helps to explain a variety of slopes observed in high-redshift disc galaxies. This scenario helps to explain the positive slope of the metallicity-rotation velocity relation observed for the Galactic thick disc. On the other hand, radial mixing flattens the slope of an existing gradient.

  6. Lin28 sustains early renal progenitors and induces Wilms tumor

    Science.gov (United States)

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  7. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Science.gov (United States)

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

    2018-01-01

    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

  8. Cancer Progenitor Cells: The Result of an Epigenetic Event?

    Science.gov (United States)

    Lapinska, Karolina; Faria, Gabriela; McGonagle, Sandra; Macumber, Kate Morgan; Heerboth, Sarah; Sarkar, Sibaji

    2018-01-01

    The concept of cancer stem cells was proposed in the late 1990s. Although initially the idea seemed controversial, the existence of cancer stem cells is now well established. However, the process leading to the formation of cancer stem cells is still not clear and thus requires further research. This article discusses epigenetic events that possibly produce cancer progenitor cells from predisposed cells by the influence of their environment. Every somatic cell possesses an epigenetic signature in terms of histone modifications and DNA methylation, which are obtained during lineage-specific differentiation of pluripotent stem cells, which is specific to that particular tissue. We call this signature an epigenetic switch. The epigenetic switch is not fixed. Our epigenome alters with aging. However, depending on the predisposition of the cells of a particular tissue and their microenvironment, the balance of the switch (histone modifications and the DNA methylation) may be tilted to immortality in a few cells, which generates cancer progenitor cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Using Strong Gravitational Lensing to Identify Fossil Group Progenitors

    Science.gov (United States)

    Johnson, Lucas E.; Irwin, Jimmy A.; White, Raymond E., III; Wong, Ka-Wah; Maksym, W. Peter; Dupke, Renato A.; Miller, Eric D.; Carrasco, Eleazar R.

    2018-04-01

    Fossil galaxy systems are classically thought to be the end result of galaxy group/cluster evolution, as galaxies experiencing dynamical friction sink to the center of the group potential and merge into a single, giant elliptical that dominates the rest of the members in both mass and luminosity. Most fossil systems discovered lie within z fossil criteria within the look forward time. Since strong gravitational lensing preferentially selects groups merging along the line of sight, or systems with a high mass concentration like fossil systems, we searched the CASSOWARY survey of strong-lensing events with the goal of determining whether lensing systems have any predisposition to being fossil systems or progenitors. We find that ∼13% of lensing groups are identified as traditional fossils while only ∼3% of nonlensing control groups are. We also find that ∼23% of lensing systems are traditional fossil progenitors compared to ∼17% for the control sample. Our findings show that strong-lensing systems are more likely to be fossil/pre-fossil systems than comparable nonlensing systems. Cumulative galaxy luminosity functions of the lensing and nonlensing groups also indicate a possible, fundamental difference between strong-lensing and nonlensing systems’ galaxy populations, with lensing systems housing a greater number of bright galaxies even in the outskirts of groups.

  10. Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability.

    Directory of Open Access Journals (Sweden)

    Tania I Fuentes

    Full Text Available Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.

  11. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    Science.gov (United States)

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  12. Pancreatic β-cell regeneration: Facultative or dedicated progenitors?

    Science.gov (United States)

    Afelik, Solomon; Rovira, Meritxell

    2017-04-15

    The adult pancreas is only capable of limited regeneration. Unlike highly regenerative tissues such as the skin, intestinal crypts and hematopoietic system, no dedicated adult stem cells or stem cell niche have so far been identified within the adult pancreas. New β cells have been shown to form in the adult pancreas, in response to high physiological demand or experimental β-cell ablation, mostly by replication of existing β cells. The possibility that new β cells are formed from other sources is currently a point of major controversy. Under particular injury conditions, fully differentiated pancreatic duct and acinar cells have been shown to dedifferentiate into a progenitor-like state, however the extent, to which ductal, acinar or other endocrine cells contribute to restoring pancreatic β-cell mass remains to be resolved. In this review we focus on regenerative events in the pancreas with emphasis on the restoration of β-cell mass. We present an overview of regenerative responses noted within the different pancreatic lineages, following injury. We also highlight the intrinsic plasticity of the adult pancreas that allows for inter-conversion of fully differentiated pancreatic lineages through manipulation of few genes or growth factors. Taken together, evidence from a number of studies suggest that differentiated pancreatic lineages could act as facultative progenitor cells, but the extent to which these contribute to β-cell regeneration in vivo is still a matter of contention. Copyright © 2016. Published by Elsevier B.V.

  13. Progenitor outgrowth from the niche in Drosophila trachea is guided by FGF from decaying branches.

    Science.gov (United States)

    Chen, Feng; Krasnow, Mark A

    2014-01-10

    Although there has been progress identifying adult stem and progenitor cells and the signals that control their proliferation and differentiation, little is known about the substrates and signals that guide them out of their niche. By examining Drosophila tracheal outgrowth during metamorphosis, we show that progenitors follow a stereotyped path out of the niche, tracking along a subset of tracheal branches destined for destruction. The embryonic tracheal inducer branchless FGF (fibroblast growth factor) is expressed dynamically just ahead of progenitor outgrowth in decaying branches. Knockdown of branchless abrogates progenitor outgrowth, whereas misexpression redirects it. Thus, reactivation of an embryonic tracheal inducer in decaying branches directs outgrowth of progenitors that replace them. This explains how the structure of a newly generated tissue is coordinated with that of the old.

  14. Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

    Science.gov (United States)

    Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

    2015-07-01

    The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  15. Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development.

    Science.gov (United States)

    Serinagaoglu, Yelda; Paré, Joshua; Giovannini, Marco; Cao, Xinwei

    2015-02-01

    Molecular mechanisms governing the maintenance and proliferation of dorsal root ganglia (DRG) progenitors are largely unknown. Here we reveal that the Hippo pathway regulates the expansion of DRG progenitors and glia during mammalian DRG development. The key effectors of this pathway, transcriptional coactivators Yap and Taz, are expressed in DRG progenitors and glia during DRG development but are at least partially inhibited from activating transcription. Aberrant YAP activation leads to overexpansion of DRG progenitor and glial populations. We further show that the Neurofibromatosis 2 (Nf2) tumor suppressor inhibits Yap during DRG development. Loss of Nf2 leads to similar phenotypes as does YAP hyperactivation, and deleting Yap suppresses these phenotypes. Our study demonstrates that Nf2-Yap signaling plays important roles in controlling the expansion of DRG progenitors and glia during DRG development. Copyright © 2014 Elsevier Inc. All rights reserved.

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  17. Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

    2011-01-01

    Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

  18. TRASTORNOS DEL ESPECTRO AUTISTA Y EXPOSICIONES OCUPACIONALES DE LOS PROGENITORES

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    Manuel Pino-López

    2013-01-01

    Full Text Available Fundamentos: Estudios con hermanos y gemelos sugieren un componente genético en el origen del autismo que no explica su crecimiento actual. El objetivo es investigar si factores ambientales como algunas exposiciones profesionales (trabajo nocturno, manejo de disolventes y/o campos electromagnéticos incrementan la probabilidad de trastornos del espectro autista (TEA en los hijos. Métodos: Estudio observacional de casos y controles mediante análisis de expedientes de 206 niños entre 16 y 36 meses de edad evaluados en el Servicio de Atención Temprana de Ciudad Real (70 con TEA y 136 no afectados. Para medir el riesgo de TEA asociado al trabajo nocturno, con disolventes y/o campos electromagnéticos se calculó la odds ratio (OR con un intervalo de confianza (IC del 95%. Resultados: El riesgo de TEA se multiplica por 2,22 cuando un progenitor trabaja en las ocupaciones estudiadas (OR=2,22, IC 95%=1,42-3,48, destacando trabajo con disolventes (OR=2,81, IC 95%=1,28-6,17 y nocturno (OR=2,18, IC 95%=1,21-3,93. El riesgo se multiplica por 3 si la madre trabaja en estas ocupaciones (OR=3, IC95%=1,44-6,26, destacando trabajo nocturno (OR=3,47, IC 95%=1,39-8,63 y con disolventes (OR=2,88, IC 95%=1,28-6,17. El riesgo se multiplica por 1,94 si el padre trabaja en estas ocupaciones(OR=1,94, IC 95%=1,07-3,53 y por 2,81 con disolventes (OR=2,81, IC 95%=1,01-7,86. Se encontró asociación positiva entre nivel educativo de los progenitores y TEA. Conclusiones: Encontramos relación significativa entre exposición de los progenitores a los riesgos estudiados y TEA en los hijos. Los resultados sugieren la participación de alteraciones genéticas ocasionadas por factores ambientales en el origen del trastorno.

  19. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

    Science.gov (United States)

    TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

    2013-01-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in

  20. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    Science.gov (United States)

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-09

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  1. Fibro/Adipogenic Progenitors (FAPs): Isolation by FACS and Culture.

    Science.gov (United States)

    Low, Marcela; Eisner, Christine; Rossi, Fabio

    2017-01-01

    Fibro/adipogenic progenitors (FAPs ) are tissue-resident mesenchymal stromal cells (MSCs). Current literature supports a role for these cells in the homeostasis and repair of multiple tissues suggesting that FAPs may have extensive therapeutic potential in the treatment of numerous diseases. In this context, it is crucial to establish efficient and reproducible procedures to purify FAP populations from various tissues. Here, we describe a protocol for the isolation and cell culture of FAPs from murine skeletal muscle using fluorescence -activated cell sorting (FACS), which is particularly useful for experiments where high cell purity is an essential requirement. Identification, isolation, and cell culture of FAPs represent powerful tools that will help us to understand the role of these cells in different conditions and facilitate the development of safe and effective new treatments for diseases.

  2. Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

    Science.gov (United States)

    Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

    2018-01-01

    Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

  3. Imaging retinal progenitor lineages in developing zebrafish embryos.

    Science.gov (United States)

    Jusuf, Patricia; Harris, William A; Poggi, Lucia

    2013-03-01

    In this protocol, we describe how to make and analyze four dimensional (4D) movies of retinal lineage in the zebrafish embryo in vivo. 4D consists of three spatial dimensions (3D) reconstructed from stacks of confocal planes plus one time dimension. Our imaging is performed on transgenic cells that express fluorescent proteins under the control of cell-specific promoters or on cells that transiently express such reporters in specific retinal cell progenitors. An important aspect of lineage tracing is the ability to follow individual cells as they undergo multiple cell divisions, final migration, and differentiation. This may mean many hours of 4D imaging, requiring that cells be kept healthy and maintained under conditions suitable for normal development. The longest movies we have made are ∼50 h. By analyzing these movies, we can see when a specific cell was born and who its sister was, allowing us to reconstruct its retinal lineages in vivo.

  4. Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus

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    Maude Dumont-Lagacé

    2017-12-01

    Full Text Available Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs. Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of this study were therefore (i to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury and (ii to characterize their phenotypic and molecular profiles using flow cytometry, immunohistology, and transcriptome sequencing. We report that while UEA1+ cells cycle the most in steady state, they are greatly affected by irradiation, leading to cell loss and proliferative arrest following acute thymic involution. On the opposite, the UEA1– subset of quiescent TECs is radioresistant and proliferate in situ following acute thymic involution, thereby contributing to thymic regeneration in 28- to 30-week-old mice. UEA1– quiescent TECs display an undifferentiated phenotype (co-expression of K8 and K5 cytokeratins and express high levels of genes that regulate stem cell activity in different tissues (e.g., Podxl and Ptprz1. In addition, two features suggest that UEA1– quiescent TECs occupy discrete stromal niches: (i their preferential location in clusters adjacent to the cortico-medullary junction and (ii their high expression of genes involved in cross talk with mesenchymal cells. The ability of UEA1– quiescent TECs to participate to TEC regeneration qualifies them as in vivo progenitor cells particularly relevant in the context of regeneration following acute thymic injury.

  5. Presence of stem/progenitor cells in the rat penis.

    Science.gov (United States)

    Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng; Lue, Tom F

    2015-01-15

    Tissue resident stem cells are believed to exist in every organ, and their identification is commonly done using a combination of immunostaining for putative stem cell markers and label-retaining cell (LRC) strategy. In this study, we employed these approaches to identify potential stem cells in the penis. Newborn rats were intraperitoneally injected with thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), and their penis was harvested at 7 h, 3 days, 1 week, and 4 weeks. It was processed for EdU stains and immunofluorescence staining for stem cell markers A2B5, PCNA, and c-kit. EdU-positive cells were counted for each time point and co-localized with each stem cell marker, then isolated and cultured in vitro followed by their characterization using flowcytometry and immunofluorescence. At 7 h post-EdU injection, 410 ± 105.3 penile corporal cells were labeled in each cross-section (∼28%). The number of EdU-positive cells at 3 days increased to 536 ± 115.6, while their percentage dropped to 25%. Progressively fewer EdU-positive cells were present in the sacrificed rat penis at longer time points (1 and 4 weeks). They were mainly distributed in the subtunic and perisinusoidal spaces, and defined as subtunic penile progenitor cells (STPCs) and perisinusoidal penile progenitor cells (PPCs). These cells expressed c-kit, A2B5, and PCNA. After culturing in vitro, only ∼0.324% corporal cells were EdU-labeled LRCs and expressed A2B5/PCNA. Therefore, labeling of penis cells by EdU occurred randomly, and label retaining was not associated with expression of c-kit, A2B5, or PCNA. The penile LRCs are mainly distributed within the subtunic and perisinusoidal space.

  6. Progenitors of low-luminosity Type II-Plateau supernovae

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    Lisakov, Sergey M.; Dessart, Luc; Hillier, D. John; Waldman, Roni; Livne, Eli

    2018-01-01

    The progenitors of low-luminosity Type II-Plateau supernovae (SNe II-P) are believed to be red supergiant (RSG) stars, but there is much disparity in the literature concerning their mass at core collapse and therefore on the main sequence. Here, we model the SN radiation arising from the low-energy explosion of RSG stars of 12, 25 and 27 M⊙ on the main sequence and formed through single star evolution. Despite the narrow range in ejecta kinetic energy (2.5-4.2 × 1050 erg) in our model set, the SN observables from our three models are significantly distinct, reflecting the differences in progenitor structure (e.g. surface radius, H-rich envelope mass and He-core mass). Our higher mass RSG stars give rise to Type II SNe that tend to have bluer colours at early times, a shorter photospheric phase, and a faster declining V-band light curve (LC) more typical of Type II-linear SNe, in conflict with the LC plateau observed for low-luminosity SNe II. The complete fallback of the CO core in the low-energy explosions of our high-mass RSG stars prevents the ejection of any 56Ni (nor any core O or Si), in contrast to low-luminosity SNe II-P, which eject at least 0.001 M⊙ of 56Ni. In contrast to observations, Type II SN models from higher mass RSGs tend to show an H α absorption that remains broad at late times (due to a larger velocity at the base of the H-rich envelope). In agreement with the analyses of pre-explosion photometry, we conclude that low-luminosity SNe II-P likely arise from low-mass rather than high-mass RSG stars.

  7. Two populations of progenitors for Type Ia supernovae?

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    Mannucci, F.; Della Valle, M.; Panagia, N.

    2006-08-01

    We use recent observations of the evolution of the Type Ia supernova (SN Ia) rate with redshift, the dependence of the SN Ia rate on the colours of the parent galaxies, and the enhancement of the SN Ia rate in radio-loud early-type galaxies to derive on robust empirical grounds, the delay time distribution (DTD) between the formation of the progenitor star and its explosion as an SN. Our analysis finds: (i) delay times as long as 3-4 Gyr, derived from observations of SNe Ia at high redshift, cannot reproduce the dependence of the SN Ia rate on the colours and on the radio-luminosity of the parent galaxies, as observed in the local Universe; (ii) the comparison between observed SN rates and a grid of theoretical `single-population' DTDs shows that only a few of them are possibly consistent with observations. The most successful models are all predicting a peak of SN explosions soon after star formation and an extended tail in the DTD, and can reproduce the data but only at a modest statistical confidence level; (iii) present data are best matched by a bimodal DTD, in which about 50 per cent of SNe Ia (dubbed `prompt' SNe Ia) explode soon after their stellar birth, in a time of the order of 108 yr, while the remaining 50 per cent (`tardy' SNe Ia) have a much wider distribution, well described by an exponential function with a decay time of about 3 Gyr. The presence in the DTD of both a strong peak at early times and a prolonged exponential tail, coupled with the well-established bimodal distribution of the decay rate (Δm15) and the systematic difference observed in the expansion velocities of the ejecta of SNe Ia in ellipticals and spirals, suggests the existence of two classes of progenitors. We discuss the cosmological implications of this result and make simple predictions, which are testable with future instrumentation.

  8. Characterization of vascular endothelial progenitor cells from chicken bone marrow

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    Bai Chunyu

    2012-05-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC are a type of stem cell used in the treatment of atherosclerosis, vascular injury and regeneration. At present, most of the EPCs studied are from human and mouse, whereas the study of poultry-derived EPCs has rarely been reported. In the present study, chicken bone marrow-derived EPCs were isolated and studied at the cellular level using immunofluorescence and RT-PCR. Results We found that the majority of chicken EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P 1, -5 and -9 were typically “S”-shaped. The viability of chicken EPCs, before and after cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1 uptake assays and immunofluorescent detection of the cell surface markers CD34, CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation of endothelial-specific Weibel-Palade bodies using transmission electron microscopy further confirmed that the cells were of endothelial lineage. In addition, chicken EPCs differentiated into endothelial cells and smooth muscle cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the chicken EPCs retained multipotency in vitro. Conclusions These results suggest that chicken EPCs not only have strong self-renewal capacity, but also the potential to differentiate into endothelial and smooth muscle cells. This research provides theoretical basis and experimental evidence for potential therapeutic application of endothelial progenitor cells in the treatment of atherosclerosis, vascular injury and diabetic complications.

  9. PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud.

    Science.gov (United States)

    Norrie, Jacqueline L; Li, Qiang; Co, Swanie; Huang, Bau-Lin; Ding, Ding; Uy, Jann C; Ji, Zhicheng; Mackem, Susan; Bedford, Mark T; Galli, Antonella; Ji, Hongkai; Vokes, Steven A

    2016-12-15

    During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd.

  10. Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors

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    Supreet Agarwal

    2015-12-01

    Full Text Available Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.

  11. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.

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    Subhra Prakash Hui

    Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.

  12. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

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    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  13. Bone marrow niche-inspired, multi-phase expansion of megakaryocytic progenitors with high polyploidization potential

    Science.gov (United States)

    Panuganti, Swapna; Papoutsakis, Eleftherios T.; Miller, William M.

    2010-01-01

    Background Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization, and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. Methods CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo), and all combinations of Interleukin (IL)-3, IL-6, IL-11, and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide to enhance polyploidization. Results Using Tpo+SCF+IL-3+IL-11, we obtained 3.5 CD34+CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2/pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. Nicotinamide more than doubled the percentage of high-ploidy Mks to 40%. Discussion We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed nicotinamide addition will greatly increase high-ploidy Mk production. PMID:20482285

  14. Bone marrow niche-inspired, multiphase expansion of megakaryocytic progenitors with high polyploidization potential.

    Science.gov (United States)

    Panuganti, Swapna; Papoutsakis, Eleftherios T; Miller, William M

    2010-10-01

    Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo) and all combinations of Interleukin (IL)-3, IL-6, IL-11 and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide (NIC) to enhance polyploidization. Using Tpo + SCF + IL-3 + IL-11, we obtained 3.5 CD34+ CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2 /pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. NIC more than doubled the percentage of high-ploidy Mks to 40%. We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed NIC addition will greatly increase high-ploidy Mk production.

  15. Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

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    Natalia Malinovskaya

    2016-12-01

    Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

  16. The Progenitors of Local Ultra-massive Galaxies Across Cosmic Time

    DEFF Research Database (Denmark)

    Marchesini, Danilo; Muzzin, Adam; Stefanon, Mauro

    2014-01-01

    in age of $z=0$ UMGs as derived from their fossil records. The progenitors of local UMGs, including the star-forming ones, never lived on the blue cloud since $z=3$. We propose an alternative path for the formation of local UMGs that refines previously proposed pictures and that is fully consistent......-forming galaxies progressively increases, with the progenitors at $2z 1$, whereas the remaining was assembled via merging from $z\\sim 1$ to the present. Most of the quenching of the star-forming progenitors happened between $z=2.75$ and $z=1.25$, in good agreement with the typical formation redshift and scatter...

  17. Violencia Filio Parental: Comparando lo que informan los adolescentes y sus progenitores

    OpenAIRE

    Calvete, Esther; Orue, Izaskun; González-Cabrera, Joaquín

    2017-01-01

    El objetivo principal del presente estudio fue examinar la consistencia de los informes de progenitores e hijos a la hora de informar sobre la violencia filio-parental en una muestra comunitaria. Como objetivo secundario, se exploraron las propiedades psicométricas de la versión para progenitores del Cuestionario de Violencia Filio-Parental (Calvete, Gámez-Guadix et al., 2013). Participaron en el estudio un total de 880 adolescentes (51.70% chicas, entre 13 y 19 años) y sus progenitores (76....

  18. An in vitro clonogenic assay to assess radiation damage in rat CNS glial progenitor cells

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Verhagen, I.; Kogel, A.J. van der

    1990-01-01

    Normal glial progenitor cells can be isolated from the rat central nervous system (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers are able to support and stimulate explanted glial progenitor cells to proliferate. Employing these in vitro interactions of specific glial cell types, an in vivo-in vitro clonogenic assay has been developed. This method offers the possibility to study the intrinsic radiosensitivity, repair and regeneration of glial progenitor cells after in vitro or in vivo irradiation. (author)

  19. Relative sea level in the Western Mediterranean basin: A regional test of the ICE-7G_NA (VM7) model and a constraint on late Holocene Antarctic deglaciation

    Science.gov (United States)

    Roy, Keven; Peltier, W. R.

    2018-03-01

    The Mediterranean Basin is a region of special interest in the study of past and present relative sea level evolution, given its location south of the ice sheets that covered large fractions of Northern Europe during the last glaciation, the large number of biological, geological and archaeological sea level indicators that have been retrieved from its coastal regions, as well as its high density of modern coastal infrastructure. Models of the Glacial Isostatic Adjustment (GIA) process provide reconstructions of past relative sea level evolution, and can be tested for validity against past sea level indicators from the region. It is demonstrated herein that the latest ICE-7G_NA (VM7) model of the GIA process, the North American component of which was refined using a full suite of geophysical observables, is able to reconcile the vast majority of uniformly analyzed relative sea level constraints available for the Western part of the Mediterranean basin, a region to which it was not tuned. We also revisit herein the previously published interpretations of relative sea level information obtained from Roman-era coastal Mediterranean "fish tanks", analyze the far-field influence of the rate of late Holocene Antarctic ice sheet melting history on the exceptionally detailed relative sea level history available from southern Tunisia, and extend the analysis to complementary constraints on the history of Antarctic ice-sheet melting available from islands in the equatorial Pacific Ocean. The analyses reported herein provide strong support for the global "exportability" of the ICE-7G_NA (VM7) model, a result that speaks directly to the ability of spherically symmetric models of the internal viscoelastic structure to explain globally distributed observations, while also identifying isolated regions of remaining misfit which will benefit from further study.

  20. Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

    International Nuclear Information System (INIS)

    Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

    2005-01-01

    The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

  1. In vitro studies on the radiosensitivity of multipotent hemopoietic progenitors in canine bone marrow

    International Nuclear Information System (INIS)

    Kreja, L.; Weinsheimer, W.; Nothdurft, W.

    1991-01-01

    The in vitro radiation response to 280-kV x-rays (does rate 72 cGy/min) of multipotent hemopoietic progenitor cells, mixed colony-forming units (CFU-mix), from canine bone marrow was assayed and compared to the radiation response characteristics of early erythroid progenitors, erythroid burst-forming units (BFU-E). To improve the colony-forming efficiency, the effect of various bone marrow cell separation techniques on colony formation of both progenitors was examined. The separation of bone marrow aspirates by discontinuous buoyant gradient centrifugation using the lymphocyte separation medium Lymphoprep with a density of 1.070 g/ml allowed the establishment of reproducible survival curves. The survival curves for both progenitors were strictly exponential, and CFU-mix were found to be more radiosensitive (D0 = 12 ± 2 cGy) than BFU-E (D0 = 16 ± 2 cGy)

  2. PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

    Science.gov (United States)

    Gaber, Zachary B; Butler, Samantha J; Novitch, Bennett G

    2013-10-01

    Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.

  3. Establishment and characterization of a unique 1 microm diameter liver-derived progenitor cell line.

    Science.gov (United States)

    Aravalli, Rajagopal N; Behnan Sahin, M; Cressman, Erik N K; Steer, Clifford J

    2010-01-01

    Liver-derived progenitor cells (LDPCs) are recently identified novel stem/progenitor cells from healthy, unmanipulated adult rat livers. They are distinct from other known liver stem/progenitor cells such as the oval cells. In this study, we have generated a LDPC cell line RA1 by overexpressing the simian virus 40 (SV40) large T antigen (TAg) in primary LDPCs. This cell line was propagated continuously for 55 passages in culture, after which it became senescent. Interestingly, following transformation with SV40 TAg, LDPCs decreased in size significantly and the propagating cells measured 1 microm in diameter. RA1 cells proliferated in vitro with a doubling time of 5-7 days, and expressed cell surface markers of LDPCs. In this report, we describe the characterization of this novel progenitor cell line that might serve as a valuable model to study liver cell functions and stem cell origin of liver cancers. Copyright 2009 Elsevier Inc. All rights reserved.

  4. EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

    Science.gov (United States)

    Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

    2017-11-01

    Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells.

    Science.gov (United States)

    Reyes, M; Verfaillie, C M

    2001-06-01

    Mesenchymal stem cells were isolated and a subpopulation of cells--multipotent adult progenitor cells--were identified that have the potential for multilineage differentiation. Their ability to engraft and differentiate in vivo is under investigation.

  6. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

    NARCIS (Netherlands)

    Smeets, B.; Angelotti, M.L.; Rizzo, P.; Dijkman, H.; Lazzeri, E.; Mooren, F.; Ballerini, L.; Parente, E.; Sagrinati, C.; Mazzinghi, B.; Ronconi, E.; Becherucci, F.; Benigni, A.; Steenbergen, E.; Lasagni, L.; Remuzzi, G.; Wetzels, J.F.M.; Romagnani, P.

    2009-01-01

    Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner

  7. Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

    DEFF Research Database (Denmark)

    Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F

    2013-01-01

    Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can...... be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate...... in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region...

  8. ON THE PROGENITOR OF THE TYPE II-PLATEAU SN 2008cn in NGC 4603

    International Nuclear Information System (INIS)

    Elias-Rosa, Nancy; Van Dyk, Schuyler D.; Li, Weidong; Filippenko, Alexei V.; Foley, Ryan J.; Smith, Nathan; Morrell, Nidia; Gonzalez, Sergio; Hamuy, Mario; Cuillandre, Jean-Charles

    2009-01-01

    A trend is emerging regarding the progenitor stars that give rise to the most common core-collapse supernovae (SNe), those of Type II-Plateau (II-P): they generally appear to be red supergiants with a limited range of initial masses, ∼8-16 M sun . Here, we consider another example, SN 2008cn, in the nearly face-on spiral galaxy NGC 4603. Even with limited photometric data, it appears that SN 2008cn is not a normal SN II-P, but is of the high-luminosity subclass. Through comparison of pre- and post-explosion images obtained with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope, we have isolated a supergiant star prior to explosion at nearly the same position as the SN. We provide evidence that this supergiant may well be the progenitor of the SN, although this identification is not entirely unambiguous. This is exacerbated by the distance to the host galaxy, 33.3 Mpc, making SN 2008cn the most distant SN II-P yet for which an attempt has been made to identify a progenitor star in pre-SN images. The progenitor candidate has a more yellow color ([V - I] 0 = 0.98 mag and T eff = 5200 ± 300 K) than generally would be expected and, if a single star, would require that it exploded during a 'blue loop' evolutionary phase, which is theoretically not expected to occur. Nonetheless, we estimate an initial mass of M ini = 15 ± 2 M sun for this star, which is within the expected mass range for SN II-P progenitors. The yellower color could also arise from the blend of two or more stars, such as a red supergiant and a brighter, blue supergiant. Such a red supergiant hidden in this blend could instead be the progenitor and would also have an initial mass within the expected progenitor mass range. Furthermore, the yellow supergiant could be in a massive, interacting binary system, analogous to the possible yellow supergiant progenitor of the high-luminosity SN II-P 2004et. Finally, if the yellow supergiant is not the progenitor, or is not a stellar

  9. Regulated proliferation of primitive hematopoietic progenitor cells in long-term human marrow cultures

    International Nuclear Information System (INIS)

    Cashman, J.; Eaves, A.C.; Eaves, C.J.

    1985-01-01

    We have examined the cycling status of various classes of erythroid and granulopoietic progenitor populations maintained for many weeks in standard normal long-term human marrow cultures. These were initiated with a single inoculum of marrow aspirate and were routinely fed by weekly removal of half of the nonadherent cells and replacement of half of the growth medium. Progenitors of large erythroid colonies (more than eight erythroblast clusters) present in the nonadherent fraction and progenitors of small granulocyte/macrophage colonies (fewer than 500 cells) present in both the nonadherent and adherent fractions were found to be actively cycling at all times examined (28% to 63% kill following a 20-minute exposure to 20 microCi/mL of high specific activity 3 H-thymidine). In contrast, progenitors of large granulocyte/macrophage colonies (more than 500 cells) and progenitors of large erythroid colonies (more than eight erythroblast clusters), present in the adherent layer, consistently alternated between a quiescent state at the time of each weekly medium change and a proliferating state two to three days later (0% to 13% kill and 21% to 49% kill, respectively). Additional experiments revealed that the activation of primitive progenitors in the adherent layer was not dependent on the addition of fresh glutamine or hydrocortisone, nor on the physical manipulations involved in changing the growth medium. These studies provide the first direct evidence that normal long-term human marrow cultures support the continued turnover of a variety of early hematopoietic progenitor cell types. Further, they indicate that the proliferative activity of the most primitive of these progenitors is regulated by stage-specific cell-cell interactions that are subject to manipulation

  10. Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

    OpenAIRE

    Feng, Yuliang; Wang, Yuhua; Cao, Nan; Yang, Huangtian; Wang, Yigang

    2012-01-01

    Despite significant therapeutic advances, heart failure remains the predominant cause of mortality worldwide. Currently, progenitor/stem cell biology holds great promise for a new era of cell-based therapy for salvaging the failing heart. However, the translational arm of progenitor/stem cell science is in a relatively primitive state. For the time being, the clinical trials have been both encouraging and disappointing. How to improve the engraftment, long-term survival and appropriate differ...

  11. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

    Directory of Open Access Journals (Sweden)

    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  12. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid.

    Science.gov (United States)

    Sanie-Jahromi, Fatemeh; Ahmadieh, Hamid; Soheili, Zahra-Soheila; Davari, Maliheh; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Deezagi, Abdolkhalegh; Pakravesh, Jalil; Bagheri, Abouzar

    2012-04-10

    Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  13. Wnt5a and Wnt11 are essential for second heart field progenitor development

    OpenAIRE

    Cohen, Ethan David; Miller, Mayumi F.; Wang, Zichao; Moon, Randall T.; Morrisey, Edward E.

    2012-01-01

    Wnt/β-catenin has a biphasic effect on cardiogenesis, promoting the induction of cardiac progenitors but later inhibiting their differentiation. Second heart field progenitors and expression of the second heart field transcription factor Islet1 are inhibited by the loss of β-catenin, indicating that Wnt/β-catenin signaling is necessary for second heart field development. However, expressing a constitutively active β-catenin with Islet1-Cre also inhibits endogenous Islet1 expression, reflectin...

  14. Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

    Directory of Open Access Journals (Sweden)

    Nicolas Christoforou

    Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological

  15. DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue

    OpenAIRE

    Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.

    2010-01-01

    Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintena...

  16. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

    OpenAIRE

    Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua

    2015-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells ...

  17. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

    2007-01-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

  18. Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors.

    Science.gov (United States)

    Henry, Curtis J; Casás-Selves, Matias; Kim, Jihye; Zaberezhnyy, Vadym; Aghili, Leila; Daniel, Ashley E; Jimenez, Linda; Azam, Tania; McNamee, Eoin N; Clambey, Eric T; Klawitter, Jelena; Serkova, Natalie J; Tan, Aik Choon; Dinarello, Charles A; DeGregori, James

    2015-12-01

    The incidence of cancer is higher in the elderly; however, many of the underlying mechanisms for this association remain unexplored. Here, we have shown that B cell progenitors in old mice exhibit marked signaling, gene expression, and metabolic defects. Moreover, B cell progenitors that developed from hematopoietic stem cells (HSCs) transferred from young mice into aged animals exhibited similar fitness defects. We further demonstrated that ectopic expression of the oncogenes BCR-ABL, NRAS(V12), or Myc restored B cell progenitor fitness, leading to selection for oncogenically initiated cells and leukemogenesis specifically in the context of an aged hematopoietic system. Aging was associated with increased inflammation in the BM microenvironment, and induction of inflammation in young mice phenocopied aging-associated B lymphopoiesis. Conversely, a reduction of inflammation in aged mice via transgenic expression of α-1-antitrypsin or IL-37 preserved the function of B cell progenitors and prevented NRAS(V12)-mediated oncogenesis. We conclude that chronic inflammatory microenvironments in old age lead to reductions in the fitness of B cell progenitor populations. This reduced progenitor pool fitness engenders selection for cells harboring oncogenic mutations, in part due to their ability to correct aging-associated functional defects. Thus, modulation of inflammation--a common feature of aging--has the potential to limit aging-associated oncogenesis.

  19. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    Science.gov (United States)

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-06

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.

    Science.gov (United States)

    Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay

    2012-04-01

    The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.

  1. EVLA OBSERVATIONS CONSTRAIN THE ENVIRONMENT AND PROGENITOR SYSTEM OF Type Ia SUPERNOVA 2011fe

    International Nuclear Information System (INIS)

    Chomiuk, Laura; Soderberg, Alicia M.; Moe, Maxwell; Margutti, Raffaella; Fong, Wen-fai; Dittmann, Jason A.; Chevalier, Roger A.; Rupen, Michael P.; Badenes, Carles; Fransson, Claes

    2012-01-01

    We report unique Expanded Very Large Array observations of SN 2011fe representing the most sensitive radio study of a Type Ia supernova to date. Our data place direct constraints on the density of the surrounding medium at radii ∼10 15 -10 16 cm, implying an upper limit on the mass loss rate from the progenitor system of M-dot -10 M ☉ yr -1 (assuming a wind speed of 100 km s –1 ) or expansion into a uniform medium with density n CSM ∼ –3 . Drawing from the observed properties of non-conservative mass transfer among accreting white dwarfs, we use these limits on the density of the immediate environs to exclude a phase space of possible progenitor systems for SN 2011fe. We rule out a symbiotic progenitor system and also a system characterized by high accretion rate onto the white dwarf that is expected to give rise to optically thick accretion winds. Assuming that a small fraction, 1%, of the mass accreted is lost from the progenitor system, we also eliminate much of the potential progenitor parameter space for white dwarfs hosting recurrent novae or undergoing stable nuclear burning. Therefore, we rule out much of the parameter space associated with popular single degenerate progenitor models for SN 2011fe, leaving a limited phase space largely inhabited by some double degenerate systems, as well as exotic single degenerates with a sufficient time delay between mass accretion and SN explosion.

  2. DNMT1 maintains progenitor function in self-renewing somatic tissue.

    Science.gov (United States)

    Sen, George L; Reuter, Jason A; Webster, Daniel E; Zhu, Lilly; Khavari, Paul A

    2010-01-28

    Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.

  3. Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.

    Science.gov (United States)

    Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad

    2016-03-01

    This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. APC sets the Wnt tone necessary for cerebral cortical progenitor development.

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    Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

    2017-08-15

    Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

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    LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

    2008-09-19

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

  6. Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

    Science.gov (United States)

    Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

    2014-03-01

    In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

  7. Endothelial progenitor cell subsets and preeclampsia: Findings and controversies

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    Armin Attar

    2017-10-01

    Full Text Available Vascular remodeling is an essential component of gestation. Endothelial progenitor cells (EPCs play an important role in the regulation of vascular homeostasis. The results of studies measuring the number of EPCs in normal pregnancies and in preeclampsia have been highly controversial or even contradictory because of some variations in technical issues and different methodologies enumerating three distinct subsets of EPCs: circulating angiogenic cells (CAC, colony forming unit endothelial cells (CFU-ECs, and endothelial colony-forming cells (ECFCs. In general, most studies have shown an increase in the number of CACs in the maternal circulation with a progression in the gestational age in normal pregnancies, while functional capacities measured by CFU-ECs and ECFCs remain intact. In the case of preeclampsia, mobilization of CACs and ECFCs occurs in the peripheral blood of pregnant women, but the functional capacities shown by culture of the derived colony-forming assays (CFU-EC and ECFC assays are altered. Furthermore, the number of all EPC subsets will be reduced in umbilical cord blood in the case of preeclampsia. As EPCs play an important role in the homeostasis of vascular networks, the difference in their frequency and functionality in normal pregnancies and those with preeclampsia can be expected. In this review, there was an attempt to provide a justification for these controversies.

  8. On the Afterglow and Progenitor of FRB 150418

    Science.gov (United States)

    Zhang, Bing

    2016-05-01

    Keane et al. recently detected a fading radio source following FRB 150418, leading to the identification of a putative host galaxy at z = 0.492 ± 0.008. Assuming that the fading source is the afterglow of FRB 150418, I model the afterglow and constrain the isotropic energy of the explosion to be a few 1050 erg, comparable to that of a short-duration gamma-ray burst (GRB). The outflow may have a jet opening angle of ˜0.22 rad, so that the beaming-corrected energy is below 1049 erg. The results rule out most fast radio burst (FRB) progenitor models for this FRB, but may be consistent with either of the following two scenarios. The first scenario invokes a merger of an NS-NS binary, which produced an undetected short GRB and a supra-massive neutron star, which subsequently collapsed into a black hole, probably hundreds of seconds after the short GRB. The second scenario invokes a merger of a compact star binary (BH-BH, NS-NS, or BH-NS) system whose pre-merger dynamical magnetospheric activities made the FRB, which is followed by an undetected short GRB-like transient. The gravitational-wave (GW) event GW 150914 would be a sister of FRB 150418 in this second scenario. In both cases, one expects an exciting prospect of GW/FRB/GRB associations.

  9. ON THE AFTERGLOW AND PROGENITOR OF FRB 150418

    International Nuclear Information System (INIS)

    Zhang, Bing

    2016-01-01

    Keane et al. recently detected a fading radio source following FRB 150418, leading to the identification of a putative host galaxy at z = 0.492 ± 0.008. Assuming that the fading source is the afterglow of FRB 150418, I model the afterglow and constrain the isotropic energy of the explosion to be a few 10 50 erg, comparable to that of a short-duration gamma-ray burst (GRB). The outflow may have a jet opening angle of ∼0.22 rad, so that the beaming-corrected energy is below 10 49 erg. The results rule out most fast radio burst (FRB) progenitor models for this FRB, but may be consistent with either of the following two scenarios. The first scenario invokes a merger of an NS–NS binary, which produced an undetected short GRB and a supra-massive neutron star, which subsequently collapsed into a black hole, probably hundreds of seconds after the short GRB. The second scenario invokes a merger of a compact star binary (BH–BH, NS–NS, or BH–NS) system whose pre-merger dynamical magnetospheric activities made the FRB, which is followed by an undetected short GRB-like transient. The gravitational-wave (GW) event GW 150914 would be a sister of FRB 150418 in this second scenario. In both cases, one expects an exciting prospect of GW/FRB/GRB associations.

  10. Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

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    Yahui Ding

    2016-09-01

    Full Text Available Abstract Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML are largely attributed to leukemia stem cells (LSCs which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. Methods The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. Results The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C, alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. Conclusions Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.

  11. Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

    Science.gov (United States)

    Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

    2017-07-15

    Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. NEURAL PROGENITORS, PATTERNING AND ECOLOGY IN NEOCORTICAL ORIGINS

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    Francisco eAboitiz

    2013-11-01

    Full Text Available The anatomical organization of the mammalian neocortex stands out among vertebrates for its laminar and columnar arrangement, featuring vertically oriented, excitatory pyramidal neurons. The evolutionary origin of this structure is discussed here in relation to the brain organization of other amniotes, i.e. the sauropsids (reptiles and birds. Specifically, we address the developmental modifications that had to take place to generate the neocortex, and to what extent these modifications were shared by other amniote lineages or can be considered unique to mammals. In this article, we propose a hypothesis that combines the control of proliferation in neural progenitor pools with the specification of regional morphogenetic gradients, yielding different anatomical results by virtue of the differential modulation of these processes in each lineage. Thus, there is a highly conserved genetic and developmental battery that becomes modulated in different directions according to specific selective pressures. In the case of early mammals, ecological conditions like nocturnal habits and reproductive strategies are considered to have played a key role in the selection of the particular brain patterning mechanisms that led to the origin of the neocortex.

  13. Tlx controls proliferation and patterning of lateral telencephalic progenitor domains.

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    Stenman, Jan M; Wang, Bei; Campbell, Kenneth

    2003-11-19

    We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.

  14. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    Science.gov (United States)

    Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

    2016-01-01

    Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

  15. An update on ABO incompatible hematopoietic progenitor cell transplantation.

    Science.gov (United States)

    Staley, Elizabeth M; Schwartz, Joseph; Pham, Huy P

    2016-06-01

    Hematopoietic progenitor cell (HPC) transplantation has long been established as the optimal treatment for many hematologic malignancies. In the setting of allogenic HLA matched HPC transplantation, greater than 50% of unrelated donors and 30% of related donors demonstrate some degree of ABO incompatibility (ABOi), which is classified in one of three ways: major, minor, or bidirectional. Major ABOi refers to the presence of recipient isoagglutinins against the donor's A and/or B antigen. Minor ABOi occurs when the HPC product contains the isoagglutinins targeting the recipient's A and/or B antigen. Bidirectional refers to the presence of both major and minor ABOi. Major adverse events associated with ABOi HPC transplantation includes acute and delayed hemolysis, pure red cell aplasia, and delayed engraftment. ABOi HPC transplantation poses a unique challenge to the clinical transplantation unit, the HPC processing lab, and the transfusion medicine service. Therefore, it is essential that these services actively communicate with one another to ensure patient safety. This review will attempt to globally address the challenges related to ABOi HPC transplantation, with an increased focus on aspects related to the laboratory and transfusion medicine services. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.

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    Reichman, David E; Park, Laura; Man, Limor; Redmond, David; Chao, Kenny; Harvey, Richard P; Taketo, Makoto M; Rosenwaks, Zev; James, Daylon

    2018-01-08

    Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs. © 2018. Published by The Company of Biologists Ltd.

  17. Hematopoietic Stem and Progenitor Cells as Effectors in Innate Immunity

    Directory of Open Access Journals (Sweden)

    Jennifer L. Granick

    2012-01-01

    Full Text Available Recent research has shed light on novel functions of hematopoietic stem and progenitor cells (HSPC. While they are critical for maintenance and replenishment of blood cells in the bone marrow, these cells are not limited to the bone marrow compartment and function beyond their role in hematopoiesis. HSPC can leave bone marrow and circulate in peripheral blood and lymph, a process often manipulated therapeutically for the purpose of transplantation. Additionally, these cells preferentially home to extramedullary sites of inflammation where they can differentiate to more mature effector cells. HSPC are susceptible to various pathogens, though they may participate in the innate immune response without being directly infected. They express pattern recognition receptors for detection of endogenous and exogenous danger-associated molecular patterns and respond not only by the formation of daughter cells but can themselves secrete powerful cytokines. This paper summarizes the functional and phenotypic characterization of HSPC, their niche within and outside of the bone marrow, and what is known regarding their role in the innate immune response.

  18. Assembly and function of the botulinum neurotoxin progenitor complex.

    Science.gov (United States)

    Gu, Shenyan; Jin, Rongsheng

    2013-01-01

    Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

  19. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

    Science.gov (United States)

    Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

    2015-03-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

  20. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development

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    M.T. Abd El Aziz

    2015-03-01

    Full Text Available We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs, examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI. EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1. EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

  1. Bone marrow endothelial progenitors in atherosclerotic plaque resolution

    Science.gov (United States)

    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

    2013-01-01

    Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

  2. Quercetin inhibits adipogenesis of muscle progenitor cells in vitro

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    Tomoko Funakoshi

    2018-03-01

    Full Text Available Muscle satellite cells are committed myogenic progenitors capable of contributing to myogenesis to maintain adult muscle mass and function. Several experiments have demonstrated that muscle satellite cells can differentiate into adipocytes in vitro, supporting the mesenchymal differentiation potential of these cells. Moreover, muscle satellite cells may be a source of ectopic muscle adipocytes, explaining the lipid accumulation often observed in aged skeletal muscle (sarcopenia and in muscles of patients` with diabetes. Quercetin, a polyphenol, is one of the most abundant flavonoids distributed in edible plants, such as onions and apples, and possesses antioxidant, anticancer, and anti-inflammatory properties. In this study, we examined whether quercetin inhibited the adipogenesis of muscle satellite cells in vitro with primary cells from rat limbs by culture in the presence of quercetin under adipogenic conditions. Morphological observations, Oil Red-O staining results, triglyceride content analysis, and quantitative reverse transcription polymerase chain reaction revealed that quercetin was capable of inhibiting the adipogenic induction of muscle satellite cells into adipocytes in a dose-dependent manner by suppressing the transcript levels of adipogenic markers, such as peroxisome proliferator-activated receptor-γ and fatty acid binding protein 4. Our results suggested that quercetin inhibited the adipogenesis of muscle satellite cells in vitro by suppressing the transcription of adipogenic markers. Keywords: Quercetin, Muscle satellite cell, Differentiation, Intramuscular lipid

  3. Muscle Progenitor Cell Regenerative Capacity in the Torn Rotator Cuff

    Science.gov (United States)

    Meyer, Gretchen A.; Farris, Ashley L.; Sato, Eugene; Gibbons, Michael; Lane, John G.; Ward, Samuel R.; Engler, Adam J.

    2014-01-01

    Chronic rotator cuff (RC) tears affect a large portion of the population and result in substantial upper extremity impairment, shoulder weakness, pain and limited range of motion. Regardless of surgical or conservative treatment, persistent atrophic muscle changes limit functional restoration and may contribute to surgical failure. We hypothesized that deficits in the skeletal muscle progenitor (SMP) cell pool could contribute to poor muscle recovery following tendon repair. Biopsies were obtained from patients undergoing arthroscopic RC surgery. The SMP population was quantified, isolated and assayed in culture for its ability to proliferate and fuse in-vitro and in-vivo. The SMP population was larger in muscles from cuffs with partial tears compared with no tears or full thickness tears. However, SMPs from muscles in the partial tear group also exhibited reduced proliferative ability. Cells from all cuff states were able to fuse robustly in culture and engraft when injected into injured mouse muscle, suggesting that when given the correct signals, SMPs are capable of contributing to muscle hypertrophy and regeneration regardless of tear severity. The fact that this does not appear to happen in-vivo helps focus future therapeutic targets for promoting muscle recovery following rotator cuff repairs and may help improve clinical outcomes. PMID:25410765

  4. Cell cycle regulation of hematopoietic stem or progenitor cells.

    Science.gov (United States)

    Hao, Sha; Chen, Chen; Cheng, Tao

    2016-05-01

    The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

  5. ON THE AFTERGLOW AND PROGENITOR OF FRB 150418

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    Zhang, Bing, E-mail: zhang@physics.unlv.edu [Department of Physics and Astronomy, University of Nevada Las Vegas, Las Vegas, NV 89154 (United States)

    2016-05-01

    Keane et al. recently detected a fading radio source following FRB 150418, leading to the identification of a putative host galaxy at z = 0.492 ± 0.008. Assuming that the fading source is the afterglow of FRB 150418, I model the afterglow and constrain the isotropic energy of the explosion to be a few 10{sup 50} erg, comparable to that of a short-duration gamma-ray burst (GRB). The outflow may have a jet opening angle of ∼0.22 rad, so that the beaming-corrected energy is below 10{sup 49} erg. The results rule out most fast radio burst (FRB) progenitor models for this FRB, but may be consistent with either of the following two scenarios. The first scenario invokes a merger of an NS–NS binary, which produced an undetected short GRB and a supra-massive neutron star, which subsequently collapsed into a black hole, probably hundreds of seconds after the short GRB. The second scenario invokes a merger of a compact star binary (BH–BH, NS–NS, or BH–NS) system whose pre-merger dynamical magnetospheric activities made the FRB, which is followed by an undetected short GRB-like transient. The gravitational-wave (GW) event GW 150914 would be a sister of FRB 150418 in this second scenario. In both cases, one expects an exciting prospect of GW/FRB/GRB associations.

  6. SH2-inositol phosphatase 1 negatively influences early megakaryocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Lia E Perez

    Full Text Available The SH2-containing-5'inositol phosphatase-1 (SHIP influences signals downstream of cytokine/chemokine receptors that play a role in megakaryocytopoiesis, including thrombopoietin, stromal-cell-derived-Factor-1/CXCL-12 and interleukin-3. We hypothesize that SHIP might control megakaryocytopoiesis through effects on proliferation of megakaryocyte progenitors (MKP and megakaryocytes (MK.Herein, we report the megakaryocytic phenotype and MK functional assays of hematopoietic organs of two strains of SHIP deficient mice with deletion of the SHIP promoter/first exon or the inositol phosphatase domain. Both SHIP deficient strains exhibit a profound increase in MKP numbers in bone marrow (BM, spleen and blood as analyzed by flow cytometry (Lin(-c-Kit+CD41+ and functional assays (CFU-MK. SHIP deficient MKP display increased phosphorylation of Signal Transducers and Activators of Transcription 3 (STAT-3, protein kinase B (PKB/AKT and extracellular signal-regulated kinases (ERKs. Despite increased MKP content, total body number of mature MK (Lin(-c-kit(-CD41+ are not significantly changed as SHIP deficient BM contains reduced MK while spleen MK numbers are increased. Reduction of CXCR-4 expression in SHIP deficient MK may influence MK localization to the spleen instead of the BM. Endomitosis, process involved in MK maturation, was preserved in SHIP deficient MK. Circulating platelets and red blood cells are also reduced in SHIP deficient mice.SHIP may play an important role in regulation of essential signaling pathways that control early megakaryocytopoiesis in vivo.

  7. Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.

    Science.gov (United States)

    Tanaka, Miwa; Yamazaki, Yukari; Kanno, Yohei; Igarashi, Katsuhide; Aisaki, Ken-ichi; Kanno, Jun; Nakamura, Takuro

    2014-07-01

    Ewing's sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing's sarcoma-associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing's sarcoma-like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS-dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of β-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing's sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing's sarcoma and provide clues to the histogenesis of Ewing's sarcoma in bone.

  8. Infusion of megakaryocytic progenitor products generated from cord blood hematopoietic stem/progenitor cells: results of the phase 1 study.

    Directory of Open Access Journals (Sweden)

    Jiafei Xi

    Full Text Available BACKGROUND: Currently, a constant shortage in the supply of platelets has become an important medical and society challenge, especially in developing country, and the in vitro production of megakaryocytic progenitor cells (MPs from cord blood could represent an effective platelet substitute. In the present study, our objective was to determine the safety and feasibility of ex vivo generated MPs in patients. METHODS AND FINDINGS: MPs were produced and characterized from cord blood mononuclear cells under a serum free medium with cytokines. We investigated the feasibility of expansion and infusion of cord blood-derived MPs in 24 patients with advanced hematological malignancies. The primary end point was the safety and tolerability of the infusion of cord blood-derived MPs. No adverse effects were observed in patients who received ex vivo-generated cells at concentrations of up to a median value of 5.45 × 10(6cells/kg of body weight. With one year follow-up, acute and chronic GVHD had not been observed among patients who received MPs infusion, even without ABO blood group and HLA typing matching. CONCLUSIONS: These initial results in patients are very encouraging. They suggest that infusion of cord blood-derived MPs appears safe and feasible for treatment of thrombocytopenia.

  9. Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide

    International Nuclear Information System (INIS)

    Winton, E.F.; Colenda, K.W.

    1987-01-01

    The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors

  10. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    International Nuclear Information System (INIS)

    Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng

    2009-01-01

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in type 1 diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet β-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for

  11. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Bing [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Zhan, Xiao-Rong, E-mail: xiaorongzhan@sina.com [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yi, Ran [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yang, Baofeng [Department of Pharmacology, State Key Laboratory of Biomedicine and Pharmacology, Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China)

    2009-06-12

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal

  12. Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature.

    Science.gov (United States)

    Psaltis, Peter J; Puranik, Amrutesh S; Spoon, Daniel B; Chue, Colin D; Hoffman, Scott J; Witt, Tyra A; Delacroix, Sinny; Kleppe, Laurel S; Mueske, Cheryl S; Pan, Shuchong; Gulati, Rajiv; Simari, Robert D

    2014-07-18

    Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage

  13. The Type IIb Supernova 2013df and its Cool Supergiant Progenitor

    Science.gov (United States)

    VanDyk, Schuyler D.; Zeng, Weikang; Fox, Ori D.; Cenko, S. Bradley; Clubb, Kelsey I.; Filippenko, Alexei; Foley, Ryan J.; Miller, Adam A.; Smith, Nathan; Kelly, Patrick L.; hide

    2014-01-01

    We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type II b, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less Ni-56 (is approximately less than 0.06M) was synthesized in the SN 2013df explosion than was the case for the SNe II b 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013dfis estimated to be A(sub V) = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope(HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T(sub eff) = 4250+/-100 K and a bolometric luminosity L(sub bol) =10(exp 4.94+/-0.06) Solar Luminosity. This leads to an effective radius Reff = 545+/-65 Solar Radius. The star likely had an initial mass in the range of 13-17Solar Mass; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.

  14. The type IIb supernova 2013df and its cool supergiant progenitor

    Energy Technology Data Exchange (ETDEWEB)

    Van Dyk, Schuyler D. [Spitzer Science Center/Caltech, Mail Code 220-6, Pasadena, CA 91125 (United States); Zheng, WeiKang; Fox, Ori D.; Clubb, Kelsey I.; Filippenko, Alexei V.; Kelly, Patrick L. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Cenko, S. Bradley [Astrophysics Science Division, NASA Goddard Space Flight Center, Mail Code 661, Greenbelt, MD 20771 (United States); Foley, Ryan J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Miller, Adam A. [Jet Propulsion Laboratory, MS 169-506, Pasadena, CA 91109 (United States); Smith, Nathan [Steward Observatory, University of Arizona, Tucson, AZ 85720 (United States); Lee, William H. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Apdo. Postal 70-264, Cd. Universitaria, México DF 04510 (Mexico); Ben-Ami, Sagi; Gal-Yam, Avishay, E-mail: vandyk@ipac.caltech.edu [Benoziyo Center for Astrophysics, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2014-02-01

    We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type IIb, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less {sup 56}Ni (≲ 0.06 M {sub ☉}) was synthesized in the SN 2013df explosion than was the case for the SNe IIb 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013df is estimated to be A{sub V} = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope (HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T {sub eff} = 4250 ± 100 K and a bolometric luminosity L {sub bol} = 10{sup 4.94±0.06} L {sub ☉}. This leads to an effective radius R {sub eff} = 545 ± 65 R {sub ☉}. The star likely had an initial mass in the range of 13-17 M {sub ☉}; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.

  15. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

    Science.gov (United States)

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-03-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  16. Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

    Science.gov (United States)

    Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

    2015-07-01

    Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p cell level correlated positively with the number of patient colonies (r = 0.762, p Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research

  17. Compact Binary Progenitors of Short Gamma-Ray Bursts

    Science.gov (United States)

    Giacomazzo, Bruno; Perna, Rosalba; Rezzolla, Luciano; Troja, Eleonora; Lazzati, Davide

    2013-01-01

    In recent years, detailed observations and accurate numerical simulations have provided support to the idea that mergers of compact binaries containing either two neutron stars (NSs) or an NS and a black hole (BH) may constitute the central engine of short gamma-ray bursts (SGRBs). The merger of such compact binaries is expected to lead to the production of a spinning BH surrounded by an accreting torus. Several mechanisms can extract energy from this system and power the SGRBs. Here we connect observations and numerical simulations of compact binary mergers, and use the current sample of SGRBs with measured energies to constrain the mass of their powering tori. By comparing the masses of the tori with the results of fully general-relativistic simulations, we are able to infer the properties of the binary progenitors that yield SGRBs. By assuming a constant efficiency in converting torus mass into jet energy epsilon(sub jet) = 10%, we find that most of the tori have masses smaller than 0.01 Solar M, favoring "high-mass" binary NSs mergers, i.e., binaries with total masses approx >1.5 the maximum mass of an isolated NS. This has important consequences for the gravitational wave signals that may be detected in association with SGRBs, since "high-mass" systems do not form a long-lived hypermassive NS after the merger. While NS-BH systems cannot be excluded to be the engine of at least some of the SGRBs, the BH would need to have an initial spin of approx. 0.9 or higher.

  18. The influence of electric fields on hippocampal neural progenitor cells.

    Science.gov (United States)

    Ariza, Carlos Atico; Fleury, Asha T; Tormos, Christian J; Petruk, Vadim; Chawla, Sagar; Oh, Jisun; Sakaguchi, Donald S; Mallapragada, Surya K

    2010-12-01

    The differentiation and proliferation of neural stem/progenitor cells (NPCs) depend on various in vivo environmental factors or cues, which may include an endogenous electrical field (EF), as observed during nervous system development and repair. In this study, we investigate the morphologic, phenotypic, and mitotic alterations of adult hippocampal NPCs that occur when exposed to two EFs of estimated endogenous strengths. NPCs treated with a 437 mV/mm direct current (DC) EF aligned perpendicularly to the EF vector and had a greater tendency to differentiate into neurons, but not into oligodendrocytes or astrocytes, compared to controls. Furthermore, NPC process growth was promoted perpendicularly and inhibited anodally in the 437 mV/mm DC EF. Yet fewer cells were observed in the DC EF, which in part was due to a decrease in cell viability. The other EF applied was a 46 mV/mm alternating current (AC) EF. However, the 46 mV/mm AC EF showed no major differences in alignment or differentiation, compared to control conditions. For both EF treatments, the percent of mitotic cells during the last 14 h of the experiment were statistically similar to controls. Reported here, to our knowledge, is the first evidence of adult NPC differentiation affected in an EF in vitro. Further investigation and application of EFs on stem cells is warranted to elucidate the utility of EFs to control phenotypic behavior. With progress, the use of EFs may be engineered to control differentiation and target the growth of transplanted cells in a stem cell-based therapy to treat nervous system disorders.

  19. Norepinephrine stimulates mobilization of endothelial progenitor cells after limb ischemia.

    Directory of Open Access Journals (Sweden)

    Qijun Jiang

    Full Text Available OBJECTIVE: During several pathological processes such as cancer progression, thermal injury, wound healing and hindlimb ischemia, the mobilization of endothelial progenitor cells (EPCs mobilization was enhanced with an increase of sympathetic nerve activity and norepinephrine (NE secretion, yet the cellular and molecular mechanisms involved in the effects of NE on EPCs has less been investigated. METHODS AND RESULTS: EPCs from BMs, peripheral circulation and spleens, the VEGF concentration in BM, skeletal muscle, peripheral circulation and spleen and angiogenesis in ischemic gastrocnemius were quantified in mice with hindlimbs ischemia. Systemic treatment of NE significantly increased EPCs number in BM, peripheral circulation and spleen, VEGF concentration in BM and skeletal muscle and angiogenesis in ischemic gastrocnemius in mice with hind limb ischemia, but did not affair VEGF concentration in peripheral circulation and spleen. EPCs isolated from healthy adults were cultured with NE in vitro to evaluate proliferation potential, migration capacity and phosphorylations of Akt and eNOS signal moleculars. Treatment of NE induced a significant increase in number of EPCs in the S-phase in a dose-dependent manner, as well as migrative activity of EPCs in vitro (p<0.05. The co-treatment of Phentolamine, I127, LY294002 and L-NAME with NE blocked the effects of NE on EPCs proliferation and migration. Treatment with NE significantly increased phosphorylation of Akt and eNOS of EPCs. Addition of phentolamine and I127 attenuated the activation of Akt/eNOS pathway, but metoprolol could not. Pretreatment of mice with either Phentolamine or I127 significantly attenuated the effects of NE on EPCs in vivo, VEGF concentration in BM, skeletal muscle and angiogenesis in ischemic gastrocnemius, but Metoprolol did not. CONCLUSION: These results unravel that sympathetic nervous system regulate EPCs mobilization and their pro-angiogenic capacity via α adrenoceptor

  20. Radiosensitivity of human haematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    Kato, Kengo; Kashiwakura, Ikuo; Omori, Atsuko

    2013-01-01

    The haematopoietic system is regenerative tissue with a high proliferative potential; therefore, haematopoietic stem cells (HSCs) are sensitive to extracellular oxidative stress caused by radiation and chemotherapeutic agents. An understanding of this issue can help predict haematopoietic recovery from radiation exposure as well as the extent of radiation damage to the haematopoietic system. In the present study, the radiosensitivity of human lineage-committed myeloid haematopoietic stem/progenitor cells (HSPCs), including colony-forming unit–granulocyte macrophage, burst-forming unit–erythroid and colony-forming unit–granulocyte–erythroid–macrophage–megakaryocyte cells, which are contained in adult individual peripheral blood (PB) and fetus/neonate placental/umbilical cord blood (CB), were studied. The PB of 59 healthy individual blood donors and the CB of 42 neonates were investigated in the present study. HSPCs prepared from PB and CB were exposed to 0.5 or 2 Gy x-irradiation. The results showed that large individual differences exist in the surviving fraction of cells. In the case of adult PB, a statistically significant negative correlation was observed between the surviving fraction observed at a dose of 0.5 Gy and the age of the blood donors; however, none of these correlations were observed after 2 Gy x-irradiation. In addition, seasonal and gender variation were observed in the surviving fraction of CB HSPCs. The present results suggest that there are large individual differences in the surviving fraction of HSPCs contained in both adult PB and fetus/neonate CB. In addition, some factors, including the gender, age and season of birth, affect the radiosensitivity of HSPCs, especially with a relatively low-dose exposure. (paper)

  1. Topological defects control collective dynamics in neural progenitor cell cultures

    Science.gov (United States)

    Kawaguchi, Kyogo; Kageyama, Ryoichiro; Sano, Masaki

    2017-04-01

    Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and -1/2 (half-integer due to the nematic feature that arises from the head-tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from -1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.

  2. Sun Ginseng Protects Endothelial Progenitor Cells From Senescence Associated Apoptosis

    Science.gov (United States)

    Im, Wooseok; Chung, Jin-Young; Bhan, Jaejun; Lim, Jiyeon; Lee, Soon-Tae; Chu, Kon; Kim, Manho

    2012-01-01

    Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verified that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms. PMID:23717107

  3. Characterization of Endothelial Progenitor Cell Interactions with Human Tropoelastin.

    Directory of Open Access Journals (Sweden)

    Young Yu

    Full Text Available The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs are increasingly recognized as important contributors to device re-endothelialization. Extracellular matrix proteins prominent in the vessel wall may enhance EPC-directed re-endothelialization. We examined attachment, spreading and proliferation on recombinant human tropoelastin (rhTE and investigated the mechanism and site of interaction. EPCs attached and spread on rhTE in a dose dependent manner, reaching a maximal level of 56±3% and 54±3%, respectively. EPC proliferation on rhTE was comparable to vitronectin, fibronectin and collagen. EDTA, but not heparan sulfate or lactose, reduced EPC attachment by 81±3%, while full attachment was recovered after add-back of manganese, inferring a classical integrin-mediated interaction. Integrin αVβ3 blocking antibodies decreased EPC adhesion and spreading on rhTE by 39±3% and 56±10% respectively, demonstrating a large contribution from this specific integrin. Attachment of EPCs on N-terminal rhTE constructs N25 and N18 accounted for most of this interaction, accompanied by comparable spreading. In contrast, attachment and spreading on N10 was negligible. αVβ3 blocking antibodies reduced EPC spreading on both N25 and N18 by 45±4% and 42±14%, respectively. In conclusion, rhTE supports EPC binding via an integrin mechanism involving αVβ3. N25 and N18, but not N10 constructs of rhTE contribute to EPC binding. The regulation of EPC activity by rhTE may have implications for modulation of the vascular biocompatibility of endovascular implants.

  4. Regulation of adult neural progenitor cell functions by purinergic signaling.

    Science.gov (United States)

    Tang, Yong; Illes, Peter

    2017-02-01

    Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca 2+ concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230. © 2016 Wiley Periodicals, Inc.

  5. Notch signaling and progenitor/ductular reaction in steatohepatitis.

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    Carola M Morell

    Full Text Available Persistent hepatic progenitor cells (HPC activation resulting in ductular reaction (DR is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis.Steatohepatitis was generated using methionine-choline deficient (MCD diet. For hepatocyte lineage tracing, R26R-YFP mice were infected with AAV8-TBG-Cre.MCD diet promoted a strong HPC/DR response that progressively diffused in the lobule, and correlated with increased fibrosis and TGF-β1 expression. Notch signaling was unchanged in laser-capture microdissected HPC/DR, whereas Notch receptors were down regulated in hepatocytes. However, in-vivo lineage tracing experiments identified discrete hepatocytes showing Notch-1 activation and expressing (the Notch-dependent Sox9. Stimulation of AML-12 hepatocyte-cell line with immobilized Jag1 induced Sox9 and down-regulated albumin and BSEP expression. TGF-β1 treatment in primary hepatic stellate cells (HSC induced Jag1 expression. In MCD diet-fed mice, αSMA-positive HSC were localized around Sox9 expressing hepatocytes, suggesting that Notch activation in hepatocytes was promoted by TGF-β1 stimulated HSC. In-vivo Notch inhibition reduced HPC response and fibrosis progression.Our data suggest that Notch signaling is an important regulator of DR and that in steatohepatitis, hepatocytes exposed to Jag1-positive HSC, contribute to pathologic DR by undergoing Notch-mediated differentiation towards an HPC-like phenotype. Given the roles of Notch in fibrosis and liver cancer, these data suggest mesenchymal expression of Jag1 as an alternative therapeutic target.

  6. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

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    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  7. [Circulating endothelial progenitor cell levels in treated hypertensive patients].

    Science.gov (United States)

    Maroun-Eid, C; Ortega-Hernández, A; Abad, M; García-Donaire, J A; Barbero, A; Reinares, L; Martell-Claros, N; Gómez-Garre, D

    2015-01-01

    Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP<140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  8. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

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    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  9. Left atrial appendages from adult hearts contain a reservoir of diverse cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Jussi V Leinonen

    Full Text Available There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA and their fates.We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45(pos cells grew with milder proteolysis, while CD45(neg cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45(pos cells expressed CD45 initially and rapidly lost its expression while differentiating.Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart.

  10. Biochemistry and biology: heart-to-heart to investigate cardiac progenitor cells.

    Science.gov (United States)

    Chimenti, Isotta; Forte, Elvira; Angelini, Francesco; Messina, Elisa; Giacomello, Alessandro

    2013-02-01

    Cardiac regenerative medicine is a rapidly evolving field, with promising future developments for effective personalized treatments. Several stem/progenitor cells are candidates for cardiac cell therapy, and emerging evidence suggests how multiple metabolic and biochemical pathways strictly regulate their fate and renewal. In this review, we will explore a selection of areas of common interest for biology and biochemistry concerning stem/progenitor cells, and in particular cardiac progenitor cells. Numerous regulatory mechanisms have been identified that link stem cell signaling and functions to the modulation of metabolic pathways, and vice versa. Pharmacological treatments and culture requirements may be exploited to modulate stem cell pluripotency and self-renewal, possibly boosting their regenerative potential for cell therapy. Mitochondria and their many related metabolites and messengers, such as oxygen, ROS, calcium and glucose, have a crucial role in regulating stem cell fate and the balance of their functions, together with many metabolic enzymes. Furthermore, protein biochemistry and proteomics can provide precious clues on the definition of different progenitor cell populations, their physiology and their autocrine/paracrine regulatory/signaling networks. Interdisciplinary approaches between biology and biochemistry can provide productive insights on stem/progenitor cells, allowing the development of novel strategies and protocols for effective cardiac cell therapy clinical translation. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Nigral dopaminergic neuron replenishment in adult mice through VE-cadherin-expressing neural progenitor cells

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    Abir A Rahman

    2017-01-01

    Full Text Available The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain's basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson's disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin+/Sox2– neural progenitor cells. We sought to further validate this finding and explore a potential atypical origin for these progenitor cells. Since neural progenitor cells have a proximal association with the vasculature of the brain and subsets of endothelial cells are Nestin+, we hypothesized that dopaminergic neural progenitors might share a common cell lineage. Therefore, we employed a VE-cadherin promoter-driven CREERT2:THlox/THlox transgenic mouse line to ablate the tyrosine hydroxylase gene from endothelial cells in adult animals. After 26 weeks, but not 13 weeks, following the genetic blockade of tyrosine hydroxylase expression in VE-cadherin+ cells, we observed a significant reduction in tyrosine hydroxylase+ neurons in the substantia nigra. The results from this genetic lineage tracing study suggest that dopaminergic neurons are replenished in adult mice by a VE-cadherin+ progenitor cell population potentially arising from an endothelial lineage.

  12. Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

    Science.gov (United States)

    Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

    2018-01-01

    Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

  13. Disturbances in the positioning, proliferation, and apoptosis of neural progenitors contribute to subcortical band heterotopia formation

    Science.gov (United States)

    Fitzgerald, MP; Covio, M; Lee, KS

    2011-01-01

    Cortical malformations are commonly associated with intractable epilepsy and other developmental disorders. Our studies utilize the tish rat, a spontaneously occurring genetic model of subcortical band heterotopia (SBH) associated with epilepsy, to evaluate the developmental events underlying SBH formation in the neocortex. Our results demonstrate that Pax6+ and Tbr2+ progenitors are mislocalized in tish+/− and tish−/− neocortex throughout neurogenesis. In addition, mislocalized tish−/− progenitors possess a longer cell cycle than wildtype or normally-positioned tish−/− progenitors, owing to a lengthened G2+M+G1 time. This mislocalization is not associated with adherens junction breakdown or loss of radial glial polarity in the ventricular zone, as assessed by immunohistochemistry against phalloidin (to identify F-actin), aPKC-λ, and Par3. However, vimentin immunohistochemistry indicates that the radial glial scaffold is disrupted in the region of the tish−/− heterotopia. Moreover, lineage tracing experiments using in utero electroporation in tish−/− neocortex demonstrate that mislocalized progenitors do not retain contact with the ventricular surface and that ventricular/subventricular zone progenitors produce neurons that migrate into both the heterotopia and cortical plate. Taken together, these findings define a series of developmental errors contributing to SBH formation that differs fundamentally from a primary error in neuronal migration. PMID:21145942

  14. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  15. DISAPPEARANCE OF THE PROGENITOR OF SUPERNOVA iPTF13bvn

    Energy Technology Data Exchange (ETDEWEB)

    Folatelli, Gastón; Bersten, Melina C. [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Instituto de Astrofísica de La Plata (IALP), CONICET, Paseo del Bosque S/N, B1900FWA La Plata (Argentina); Van Dyk, Schuyler D. [IPAC/Caltech, Mailcode 100-22, Pasadena, CA 91125 (United States); Kuncarayakti, Hanindyo; Pignata, Giuliano; Hamuy, Mario [Millennium Institute of Astrophysics (MAS), Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi; Quimby, Robert M. [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Zheng, WeiKang; Filippenko, Alexei V.; Clubb, Kelsey I. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Smith, Nathan [Steward Observatory, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Elias-Rosa, Nancy [INAF-Osservatorio Astronomico di Padova, Vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Foley, Ryan J. [Astronomy Department, University of Illinois at Urbana-Champaign, 1002 W. Green Street, Urbana, IL 61801 (United States); Miller, Adam A., E-mail: gaston.folatelli@ipmu.jp [Jet Propulsion Laboratory, 4800 Oak Grove Drive, MS 169-506, Pasadena, CA 91109 (United States)

    2016-07-10

    Supernova (SN) iPTF13bvn in NGC 5806 was the first Type Ib SN to have been tentatively associated with a progenitor in pre-explosion images. We performed deep ultraviolet (UV) and optical Hubble Space Telescope observations of the SN site ∼740 days after explosion. We detect an object in the optical bands that is fainter than the pre-explosion object. This dimming is likely not produced by dust absorption in the ejecta; thus, our finding confirms the connection of the progenitor candidate with the SN. The object in our data is likely dominated by the fading SN, implying that the pre-SN flux is mostly due to the progenitor. We compare our revised pre-SN photometry with previously proposed models. Although binary progenitors are favored, models need to be refined. In particular, to comply with our deep UV detection limit, any companion star must be less luminous than a late-O star or substantially obscured by newly formed dust. A definitive progenitor characterization will require further observations to disentangle the contribution of a much fainter SN and its environment.

  16. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.

    Science.gov (United States)

    Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H

    2015-11-24

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.

  17. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  18. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    Science.gov (United States)

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

    Science.gov (United States)

    Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

    2009-12-01

    Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

  20. Reply to Comment by W. R. Peltier, D. F. Argus, and R. Drummond on "An Assessment of the ICE6G_C (VM5a) Glacial Isostatic Adjustment Model"

    Science.gov (United States)

    Purcell, A.; Tregoning, P.; Dehecq, A.

    2018-02-01

    The empirical approximation of Purcell et al. (2011, https://doi.org/10.1029/2011GL048624) has been validated by Peltier et al. (2018, https://doi.org/10.1002/2016JB013844). In their Comment they introduced new results derived from the same ice/rheology models of ICE6G_C (VM5a) but using a different model for Antarctic bathymetry. This has greatly reduced the differences in predicted Antarctic uplift rates relative to those of Purcell et al. (2016, https://doi.org/10.1002/2015JB012742). In fact, with a ˜50% reduction in uplift rate in the Weddell Sea, the results of Peltier et al. (2018, https://doi.org/10.1002/2016JB013844) now agree more closely with the predictions of Purcell et al. (2016, https://doi.org/10.1002/2015JB012742) than with the original ICE6G_C values. Peltier et al. (2018, https://doi.org/10.1002/2016JB013844) state that the high power in their high-frequency spherical harmonic coefficients remains in their new calculations. They also claim that Purcell et al. (2016, https://doi.org/10.1002/2015JB012742) used an inaccurate loading history in deriving their velocity field. In fact, the ice load history was unchanged; to remove any ambiguity, the ice and water load histories used in the CALSEA calculations are provided in the supporting information.

  1. From here to there, progenitor cells and stem cells are everywhere in lung vascular remodeling

    Directory of Open Access Journals (Sweden)

    Rebecca L. Heise

    2016-08-01

    Full Text Available The field of stem cell biology, cell therapy and regenerative medicine has expanded almost exponentially in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD, chronic obstructive pulmonary disease (COPD, idiopathic pulmonary fibrosis (IPF or pulmonary arterial hypertension (PAH. Extensive research activity is exploring lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field.

  2. The isolation and in vitro expansion of hepatic Sca-1 progenitor cells

    International Nuclear Information System (INIS)

    Clayton, Elizabeth; Forbes, Stuart J.

    2009-01-01

    The intra-hepatic population of liver progenitor cells expands during liver injury when hepatocyte proliferation is inhibited. These cells can be purified by density gradient centrifugation and cultured. Separated by size only this population contains small cells of hematopoietic, epithelial and endothelial lineages and is thought to contain liver stem cells. The identity of liver stem cells remains unknown although there is some evidence that tissue Sca1 + CD45 - cells display progenitor cell characteristics. We identified both intra-hepatic and gall bladder Sca1 + cells following liver injury and expanded ex vivo Sca1 cells as part of heterogenous cell culture or as a purified population. We found significant difference between the proliferation of Sca-1 cells when plated on laminin or collagen I while proliferation of heterogenous population was not affected by the extracellular matrix indicating the necessity for culture of Sca1 + cells with laminin matrix or laminin producing cells in long term liver progenitor cell cultures.

  3. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification.

    Science.gov (United States)

    Moretti, Alessandra; Caron, Leslie; Nakano, Atsushi; Lam, Jason T; Bernshausen, Alexandra; Chen, Yinhong; Qyang, Yibing; Bu, Lei; Sasaki, Mika; Martin-Puig, Silvia; Sun, Yunfu; Evans, Sylvia M; Laugwitz, Karl-Ludwig; Chien, Kenneth R

    2006-12-15

    Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1(+) precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1(+) cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1(+)/Nkx2.5(+)/flk1(+) defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1(+) cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types.

  4. THE PROGENITORS OF TYPE Ia SUPERNOVAE. I. ARE THEY SUPERSOFT SOURCES?

    International Nuclear Information System (INIS)

    Di Stefano, R.

    2010-01-01

    In a canonical model, the progenitors of Type Ia supernovae (SNe Ia) are accreting, nuclear-burning white dwarfs (NBWDs), which explode when the white dwarf reaches the Chandrasekhar mass, M C . Such massive NBWDs are hot (kT ∼ 100 eV), luminous (L ∼ 10 38 erg s -1 ), and are potentially observable as luminous supersoft X-ray sources (SSSs). During the past several years, surveys for soft X-ray sources in external galaxies have been conducted. This paper shows that the results falsify the hypothesis that a large fraction of progenitors are NBWDs which are presently observable as SSSs. The data also place limits on sub-M C models. While SN Ia progenitors may pass through one or more phases of SSS activity, these phases are far shorter than the time needed to accrete most of the matter that brings them close to M C .

  5. Circumstellar matter and the nature of the SN1987A progenitor star

    International Nuclear Information System (INIS)

    Chevalier, R.A.; Fransson, C.

    1987-01-01

    The radio observations of the supernova SN1987A can be interpreted in terms of its interaction with circumstellar matter. The early turn-on of the radio emission implies a relatively low density circumstellar medium. The optical properties of the supernova imply that the progenitor star had a smaller radius than that of a typical type II supernova progenitor. The mass loss properties are consistent with this hypothesis. The authors predict the thermal X-ray luminosity of the supernova, and note that it is below the current upper limit. A bright infrared dust echo is not expected. Weak ultraviolet emission lines from circumstellar gas may be visible. Although the circumstellar density is low, it is possible that the progenitor star did lose a substantial fraction of its mass prior to the supernova explosion. (author)

  6. Progenitor cells for regenerative medicine and consequences of ART and cloning-associated epimutations.

    Science.gov (United States)

    Laprise, Shari L

    2010-06-01

    The "holy grail" of regenerative medicine is the identification of an undifferentiated progenitor cell that is pluripotent, patient specific, and ethically unambiguous. Such a progenitor cell must also be able to differentiate into functional, transplantable tissue, while avoiding the risks of immune rejection. With reports detailing aberrant genomic imprinting associated with assisted reproductive technologies (ART) and reproductive cloning, the idea that human embryonic stem cells (hESCs) derived from surplus in vitro fertilized embryos or nuclear transfer ESCs (ntESCs) harvested from cloned embryos may harbor dangerous epigenetic errors has gained attention. Various progenitor cell sources have been proposed for human therapy, from hESCs to ntESCs, and from adult stem cells to induced pluripotent stem cells (iPS and piPS cells). This review highlights the advantages and disadvantages of each of these technologies, with particular emphasis on epigenetic stability.

  7. Effect of vitamin D on endothelial progenitor cells function.

    Directory of Open Access Journals (Sweden)

    Yoav Hammer

    Full Text Available Endothelial progenitor cells (EPCs are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function.To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes.Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8% and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs, their viability (measured by MTT assay, KLF-10 levels and angiogenic markers were evaluated after 1 week of culture.In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol [EPC CFUs: 1.25 (IQR 1.0-2.0 vs. 0.5 (IQR 0.5-1.9, p < 0.001; MTT:0.62 (IQR 0.44-0.93 vs. 0.52 (IQR 0.31-0.62, p = 0.001]. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability [MTT: 0.23 (IQR 0.11-0.46 vs. 0.19 (0.09-0.39, p = 0.04], but without differences in CFU count or angiopoietic markers.In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.

  8. Increased FDG bone marrow uptake after intracoronary progenitor cell therapy

    Energy Technology Data Exchange (ETDEWEB)

    Doebert, N.; Menzel, C.; Diehl, M.; Hamscho, N.; Zaplatnikov, K.; Gruenwald, F. [Dept. of Nuclear Medicine, Univ. of Frankfurt (Germany)

    2005-02-01

    Patients with coronary artery disease who undergo FDG PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. Aim of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. Patients, methods: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3{+-}2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10{+-}1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. Results: In patients (n=70) who received PCT without G-CSF, BMU media (1.3) was slightly, but significantly higher than in the controls (1.0) (p=0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p=0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p=0.023). Leucocyte blood levels were significantly higher in patients with a BMU {>=}2.5 compared to patients with a bone marrow SUVmax<2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p=0.38). Conclusion: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplitifcation of BMU. (orig.)

  9. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

  10. Endothelial progenitor cells display clonal restriction in multiple myeloma

    International Nuclear Information System (INIS)

    Braunstein, Marc; Özçelik, Tayfun; Bağişlar, Sevgi; Vakil, Varsha; Smith, Eric LP; Dai, Kezhi; Akyerli, Cemaliye B; Batuman, Olcay A

    2006-01-01

    In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V H ). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V H primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI

  11. Interactions between endothelial progenitor cells (EPC) and titanium implant surfaces.

    Science.gov (United States)

    Ziebart, Thomas; Schnell, Anne; Walter, Christian; Kämmerer, Peer W; Pabst, Andreas; Lehmann, Karl M; Ziebart, Johanna; Klein, Marc O; Al-Nawas, Bilal

    2013-01-01

    Endothelial cells play an important role in peri-implant angiogenesis during early bone formation. Therefore, interactions between endothelial progenitor cells (EPCs) and titanium dental implant surfaces are of crucial interest. The aim of our in vitro study was to investigate the reactions of EPCs in contact with different commercially available implant surfaces. EPCs from buffy coats were isolated by Ficoll density gradient separation. After cell differentiation, EPC were cultured for a period of 7 days on different titanium surfaces. The test surfaces varied in roughness and hydrophilicity: acid-etched (A), sand-blasted-blasted and acid-etched (SLA), hydrophilic A (modA), and hydrophilic SLA (modSLA). Plastic and fibronectin-coated plastic surfaces served as controls. Cell numbers and morphology were analyzed by confocal laser scanning microscopy. Secretion of vascular endothelial growth factor (VEGF)-A was measured by enzyme-linked immunosorbent assay and expressions of iNOS and eNOS were investigated by real-time polymerase chain reaction. Cell numbers were higher in the control groups compared to the cells of titanium surfaces. Initially, hydrophilic titanium surfaces (modA and modSLA) showed lower cell numbers than hydrophobic surfaces (A and SLA). After 7 days smoother surfaces (A and modA) showed increased cell numbers compared to rougher surfaces (SLA and modSLA). Cell morphology of A, modA, and control surfaces was characterized by a multitude of pseudopodia and planar cell soma architecture. SLA and modSLA promoted small and plump cell soma with little quantity of pseudopodia. The lowest VEGF level was measured on A, the highest on modSLA. The highest eNOS and iNOS expressions were found on modA surfaces. The results of this study demonstrate that biological behaviors of EPCs can be influenced by different surfaces. The modSLA surface promotes an undifferentiated phenotype of EPCs that has the ability to secrete growth factors in great quantities. In

  12. Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

    Directory of Open Access Journals (Sweden)

    Teruyo Oishi

    Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi

  13. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    Science.gov (United States)

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

  14. Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells

    International Nuclear Information System (INIS)

    Sakai, Hiroshi; Tagawa, Yoh-ichi; Tamai, Miho; Motoyama, Hiroaki; Ogawa, Shinichiro; Soeda, Junpei; Nakata, Takenari; Miyagawa, Shinichi

    2010-01-01

    Research highlights: → Hepatic progenitor cells were isolated from the portal branch-ligated liver of mice. → Portal branch ligation-stimulated hepatic progenitor cells (PBLHCs) express Hmga2. → PBLHCs have bidirectional differentiation capability in vitro. -- Abstract: Hepatic stem/progenitor cells are one of several cell sources that show promise for restoration of liver mass and function. Although hepatic progenitor cells (HPCs), including oval cells, are induced by administration of certain hepatotoxins in experimental animals, such a strategy would be inappropriate in a clinical setting. Here, we investigated the possibility of isolating HPCs in a portal branch-ligated liver model without administration of any chemical agents. A non-parenchymal cell fraction was prepared from the portal branch-ligated or non-ligated lobe, and seeded onto plates coated with laminin. Most of the cells died, but a small number were able to proliferate. These proliferating cells were cloned as portal branch ligation-stimulated hepatic cells (PBLHCs) by the limiting dilution method. The PBLHCs expressed cytokeratin19, albumin, and Hmga2. The PBLHCs exhibited metabolic functions such as detoxification of ammonium ions and synthesis of urea on Matrigel-coated plates in the presence of oncostatin M. In Matrigel mixed with type I collagen, the PBLHCs became rearranged into cystic and tubular structures. Immunohistochemical staining demonstrated the presence of Hmga2-positive cells around the interlobular bile ducts in the portal branch-ligated liver lobes. In conclusion, successful isolation of bipotent hepatic progenitor cell clones, PBLHCs, from the portal branch-ligated liver lobes of mice provides the possibility of future clinical application of portal vein ligation to induce hepatic progenitor cells.

  15. The initial masses of the red supergiant progenitors to Type II supernovae

    Science.gov (United States)

    Davies, Ben; Beasor, Emma R.

    2018-02-01

    There are a growing number of nearby supernovae (SNe) for which the progenitor star is detected in archival pre-explosion imaging. From these images it is possible to measure the progenitor's brightness a few years before explosion, and ultimately estimate its initial mass. Previous work has shown that II-P and II-L SNe have red supergiant (RSG) progenitors, and that the range of initial masses for these progenitors seems to be limited to ≲ 17 M⊙. This is in contrast with the cut-off of 25-30 M⊙ predicted by evolutionary models, a result that is termed the `red supergiant problem'. Here we investigate one particular source of systematic error present in converting pre-explosion photometry into an initial mass, which of the bolometric correction (BC) used to convert a single-band flux into a bolometric luminosity. We show, using star clusters, that RSGs evolve to later spectral types as they approach SN, which in turn causes the BC to become larger. Failure to account for this results in a systematic underestimate of a star's luminosity, and hence its initial mass. Using our empirically motivated BCs we reappraise the II-P and II-L SNe that have their progenitors detected in pre-explosion imaging. Fitting an initial mass function to these updated masses results in an increased upper mass cut-off of Mhi = 19.0^{+2.5}_{-1.3} M⊙, with a 95 per cent upper confidence limit of <27 M⊙. Accounting for finite sample size effects and systematic uncertainties in the mass-luminosity relationship raises the cut-off to Mhi = 25 M⊙ (<33 M⊙, 95 per cent confidence). We therefore conclude that there is currently no strong evidence for `missing' high-mass progenitors to core-collapse SNe.

  16. THE ARDUOUS JOURNEY TO BLACK HOLE FORMATION IN POTENTIAL GAMMA-RAY BURST PROGENITORS

    Energy Technology Data Exchange (ETDEWEB)

    Dessart, Luc [Laboratoire d' Astrophysique de Marseille, Universite Aix-Marseille and CNRS, UMR7326, 38 rue Frederic Joliot-Curie, 13388 Marseille (France); O' Connor, Evan; Ott, Christian D., E-mail: Luc.Dessart@oamp.fr, E-mail: evanoc@tapir.caltech.edu, E-mail: cott@tapir.caltech.edu [TAPIR, Mailcode 350-17, California Institute of Technology, Pasadena, CA 91125 (United States)

    2012-07-20

    We present a quantitative study on the properties at death of fast-rotating massive stars evolved at low-metallicity-objects that are proposed as likely progenitors of long-duration {gamma}-ray bursts (LGRBs). We perform one-dimensional+rotation stellar-collapse simulations on the progenitor models of Woosley and Heger, and critically assess their potential for the formation of a black hole and a Keplerian disk (namely, a collapsar) or a proto-magnetar. We note that theoretical uncertainties in the treatment of magnetic fields and the approximate handling of rotation compromise the accuracy of stellar-evolution models. We find that only the fastest rotating progenitors achieve sufficient compactness for black hole formation while the bulk of models possess a core density structure typical of garden-variety core-collapse supernova (SN) progenitors evolved without rotation and at solar metallicity. Of the models that do have sufficient compactness for black hole formation, most of them also retain a large amount of angular momentum in the core, making them prone to a magneto-rotational explosion, therefore preferentially leaving behind a proto-magnetar. A large progenitor angular-momentum budget is often the sole criterion invoked in the community today to assess the suitability for producing a collapsar. This simplification ignores equally important considerations such as the core compactness, which conditions black hole formation, the core angular momentum, which may foster a magneto-rotational explosion preventing black hole formation, or the metallicity and the residual envelope mass which must be compatible with inferences from observed LGRB/SNe. Our study suggests that black hole formation is non-trivial, that there is room for accommodating both collapsars and proto-magnetars as LGRB progenitors, although proto-magnetars seem much more easily produced by current stellar-evolutionary models.

  17. In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice.

    Science.gov (United States)

    Río, Paula; Segovia, José Carlos; Hanenberg, Helmut; Casado, José Antonio; Martínez, Jesús; Göttsche, Kerstin; Cheng, Ngan Ching; Van de Vrugt, Henri J; Arwert, Fré; Joenje, Hans; Bueren, Juan A

    2002-09-15

    Fanconi anemia (FA) is a rare autosomal recessive disease, characterized by bone marrow failure and cancer predisposition. So far, 8 complementation groups have been identified, although mutations in FANCA account for the disease in the majority of FA patients. In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors. The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors. As observed in other FA models, the hematopoietic progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC). In addition, we observed for the first time in a FA mouse model a marked in vitro growth defect of Fanca(-/-) progenitors, either when total BM or when purified Lin(-)Sca-1(+) cells were subjected to in vitro stimulation. Liquid cultures of Fanca(-/-) BM that were stimulated with stem cell factor plus interleukin-11 produced low numbers of granulocyte macrophage colony-forming units, contained a high proportion of apoptotic cells, and generated a decreased proportion of granulocyte versus macrophage cells, compared to normal BM cultures. Aiming to correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice.

  18. Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming

    Directory of Open Access Journals (Sweden)

    Li Guo

    2017-12-01

    Full Text Available Summary: A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an “interrupted reprogramming” strategy to generate “induced progenitor-like (iPL cells” using carefully timed expression of induced pluripotent stem cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc; OSKM from non-proliferative Club cells. Interrupted reprogramming allowed controlled expansion yet preservation of lineage commitment. Under clonogenic conditions, iPL cells expanded and functioned as a bronchiolar progenitor-like population to generate mature Club cells, mucin-producing goblet cells, and cystic fibrosis transmembrane conductance regulator (CFTR-expressing ciliated epithelium. In vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted reprogramming process could be metronomically applied to achieve controlled progenitor-like proliferation. By carefully controlling the duration of expression of OSKM, iPL cells do not become pluripotent, and they maintain their memory of origin and retain their ability to efficiently return to their original phenotype. A generic technique to produce highly specified populations may have significant implications for regenerative medicine. : In this article Waddell, Nagy, and colleagues present an “interrupted reprogramming” strategy to produce highly specified functional “induced progenitor-like cells” from mature quiescent cells. They propose that careful control of the duration of transient expression of iPSC reprogramming factors (OSKM allows controlled expansion yet preservation of parental lineage without traversing the pluripotent state. Keywords: generation of induced progenitor-like cells

  19. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  20. Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

    International Nuclear Information System (INIS)

    Zhang, Yandong; Yu, Xinchun; Sun, Shuhui; Li, Qian; Xie, Yunli; Li, Qiang; Zhao, Yifan; Pei, Jianfeng; Zhang, Wenmin; Xue, Peng; Zhou, Zhijun; Zhang, Yubin

    2016-01-01

    The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors, the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.

  1. β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina

    Directory of Open Access Journals (Sweden)

    Meyers Jason R

    2012-08-01

    Full Text Available Abstract Background The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood. Results We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL. Conclusions β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that

  2. THE ARDUOUS JOURNEY TO BLACK HOLE FORMATION IN POTENTIAL GAMMA-RAY BURST PROGENITORS

    International Nuclear Information System (INIS)

    Dessart, Luc; O'Connor, Evan; Ott, Christian D.

    2012-01-01

    We present a quantitative study on the properties at death of fast-rotating massive stars evolved at low-metallicity—objects that are proposed as likely progenitors of long-duration γ-ray bursts (LGRBs). We perform one-dimensional+rotation stellar-collapse simulations on the progenitor models of Woosley and Heger, and critically assess their potential for the formation of a black hole and a Keplerian disk (namely, a collapsar) or a proto-magnetar. We note that theoretical uncertainties in the treatment of magnetic fields and the approximate handling of rotation compromise the accuracy of stellar-evolution models. We find that only the fastest rotating progenitors achieve sufficient compactness for black hole formation while the bulk of models possess a core density structure typical of garden-variety core-collapse supernova (SN) progenitors evolved without rotation and at solar metallicity. Of the models that do have sufficient compactness for black hole formation, most of them also retain a large amount of angular momentum in the core, making them prone to a magneto-rotational explosion, therefore preferentially leaving behind a proto-magnetar. A large progenitor angular-momentum budget is often the sole criterion invoked in the community today to assess the suitability for producing a collapsar. This simplification ignores equally important considerations such as the core compactness, which conditions black hole formation, the core angular momentum, which may foster a magneto-rotational explosion preventing black hole formation, or the metallicity and the residual envelope mass which must be compatible with inferences from observed LGRB/SNe. Our study suggests that black hole formation is non-trivial, that there is room for accommodating both collapsars and proto-magnetars as LGRB progenitors, although proto-magnetars seem much more easily produced by current stellar-evolutionary models.

  3. THE PROGENITOR OF SUPERNOVA 2011dh/PTF11eon IN MESSIER 51

    Energy Technology Data Exchange (ETDEWEB)

    Van Dyk, Schuyler D. [Spitzer Science Center/Caltech, Pasadena CA 91125 (United States); Li, Weidong; Cenko, S. Bradley; Silverman, Jeffrey M.; Filippenko, Alexei V. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Kasliwal, Mansi M.; Horesh, Assaf; Ofek, Eran O.; Quimby, Robert M.; Kulkarni, Shrinivas R. [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Kraus, Adam L. [Institute for Astronomy, University of Hawaii, Honolulu, HI 96822 (United States); Arcavi, Iair; Gal-Yam, Avishay; Yaron, Ofer; Polishook, David, E-mail: vandyk@ipac.caltech.edu [Department of Particle Physics and Astrophysics, Weizmann Institute of Science, 76100 Rehovot (Israel)

    2011-11-10

    We have identified a luminous star at the position of supernova (SN) 2011dh/PTF11eon, in pre-SN archival, multi-band images of the nearby, nearly face-on galaxy Messier 51 (M51) obtained by the Hubble Space Telescope with the Advanced Camera for Surveys. This identification has been confirmed, to the highest available astrometric precision, using a Keck-II adaptive-optics image. The available early-time spectra and photometry indicate that the SN is a stripped-envelope, core-collapse Type IIb, with a more compact progenitor (radius {approx} 10{sup 11} cm) than was the case for the well-studied SN IIb 1993J. We infer that the extinction to SN 2011dh and its progenitor arises from a low Galactic foreground contribution, and that the SN environment is of roughly solar metallicity. The detected object has absolute magnitude M{sup 0}{sub V} Almost-Equal-To -7.7 and effective temperature {approx}6000 K. The star's radius, {approx}10{sup 13} cm, is more extended than what has been inferred for the SN progenitor. We speculate that the detected star is either an unrelated star very near the position of the actual progenitor, or, more likely, the progenitor's companion in a mass-transfer binary system. The position of the detected star in a Hertzsprung-Russell diagram is consistent with an initial mass of 17-19 M{sub Sun }. The light of this star could easily conceal, even in the ultraviolet, the presence of a stripped, compact, very hot ({approx}10{sup 5} K), nitrogen-rich Wolf-Rayet star progenitor.

  4. Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.

    Directory of Open Access Journals (Sweden)

    Dilyana Todorova

    Full Text Available BACKGROUND: Circulating CD34(+ cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN could target progenitor cell injury by Natural Killer (NK cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+-derived Endothelial Colony Forming Cells (ECFC can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+ progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+ cells expressing FKN was identified as an independent variable inversely correlated to CD34(+ progenitor cell count. We further showed that treatment of CD34(+ circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+ progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.

  5. Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yandong; Yu, Xinchun [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Li, Qian [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Xie, Yunli [Insititute of Brain Sciences, Fudan University, Shanghai 200032 (China); Li, Qiang [Putuo District Center for Disease Control and Prevention, Shanghai 200062 (China); Zhao, Yifan; Pei, Jianfeng; Zhang, Wenmin; Xue, Peng; Zhou, Zhijun [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Zhang, Yubin, E-mail: yz001@fudan.edu.cn [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China)

    2016-12-15

    The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors, the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.

  6. A Fate Map of the Murine Pancreas Buds Reveals a Multipotent Ventral Foregut Organ Progenitor

    Science.gov (United States)

    Angelo, Jesse R.; Guerrero-Zayas, Mara-Isel; Tremblay, Kimberly D.

    2012-01-01

    The definitive endoderm is the embryonic germ layer that gives rise to the budding endodermal organs including the thyroid, lung, liver and pancreas as well as the remainder of the gut tube. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Dorsal bud progenitors are located in the medial endoderm overlying somites 2–4 between the 2 and 11 somite stage (SS). The endoderm forming the ventral pancreas bud is found in 2 distinct regions. One territory originates from the left and right lateral endoderm caudal to the anterior intestinal portal by the 6 SS and the second domain is derived from the ventral midline of the endoderm lip (VMEL). Unlike the laterally located ventral foregut progenitors, the VMEL population harbors a multipotent progenitor that contributes to the thyroid bud, the rostral cap of the liver bud, ventral midline of the liver bud and the midline of the ventral pancreas bud in a temporally restricted manner. This data suggests that the midline of the 9.5 dpc thyroid, liver and ventral pancreas buds originates from the same progenitor population, demonstrating a developmental link between all three ventral foregut buds. Taken together, these data define the location of the dorsal and ventral pancreas progenitors in the prespecified endodermal sheet and should lead to insights into the inductive events required for pancreas specification. PMID:22815796

  7. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

    NARCIS (Netherlands)

    von Lindern, M.; Zauner, W.; Mellitzer, G.; Steinlein, P.; Fritsch, G.; Huber, K.; Löwenberg, B.; Beug, H.

    1999-01-01

    Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors

  8. File list: NoD.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Neu.20.AllAg.Neural_progenitor_cells mm9 No description Neural Neural progenito...SRX346675,SRX346817 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  9. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

    Science.gov (United States)

    Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

    2017-01-01

    Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein-protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

  10. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    Haibo Shi

    2017-04-01

    Full Text Available Cochlear supporting cells (SCs have been shown to be a promising resource for hair cell (HC regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

  11. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

    Science.gov (United States)

    Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

    2017-01-01

    Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration. PMID:28491023

  12. Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients

    DEFF Research Database (Denmark)

    Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem

    2007-01-01

    Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor...

  13. Role of nutrients and mTOR signaling in the regulation of pancreatic progenitors development

    Directory of Open Access Journals (Sweden)

    Lynda Elghazi

    2017-06-01

    Full Text Available Objective: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis. Method: Pancreatic rudiments in culture were used to study the role of glucose, growth factors, and amino acids on β-cell development. The number and proliferation of pancreatic and endocrine progenitor were assessed in the presence or absence of rapamycin. The impact of mTOR signaling in vivo on pancreas development and glucose homeostasis was assessed in models deficient for mTOR or Raptor in Pdx1 expressing pancreatic progenitors. Results: We found that amino acid concentrations, and leucine in particular, enhance the number of pancreatic and endocrine progenitors and are essential for growth factor induced proliferation. Rapamycin, an mTORC1 complex inhibitor, reduced the number and proliferation of pancreatic and endocrine progenitors. Mice lacking mTOR in pancreatic progenitors exhibited hyperglycemia in neonates, hypoinsulinemia and pancreatic agenesis/hypoplasia with pancreas rudiments containing ductal structures lacking differentiated acinar and endocrine cells. In addition, loss of mTORC1 by deletion of raptor in pancreatic progenitors reduced pancreas size with reduced number of β-cells. Conclusion: Together, these results suggest that amino acids concentrations and in particular leucine modulates growth responses of pancreatic and endocrine progenitors and that mTOR signaling is critical for these responses. Inactivation of mTOR and raptor in pancreatic progenitors suggested that alterations in some of

  14. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...

  15. Periodontal Bioengineering: A Discourse in Surface Topographies, Progenitor Cells and Molecular Profiles

    Science.gov (United States)

    Dangaria, Smit J.

    2011-12-01

    Stem/progenitor cells are a population of cells capable of providing replacement cells for a given differentiated cell type. We have applied progenitor cell-based technologies to generate novel tissue-engineered implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone (AB), and periodontal ligament (PDL) are neural crest-derived entities that emerge from the dental follicle (DF) at the onset of tooth root formation. Using a systems biology approach we have identified key differences between these periodontal progenitors on the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, in addition to differences in cellular morphologies. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Secondly, we have tested the influence of natural extracellular hydroxyapatite matrices on periodontal progenitor differentiation. Dimension and structure of extracellular matrix surfaces have powerful influences on cell shape, adhesion, and gene expression. Here we show that natural tooth root topographies induce integrin-mediated extracellular matrix signaling cascades in tandem with cell elongation and polarization to generate physiological periodontium-like tissues. In this study we replanted surface topography instructed periodontal ligament progenitors (PDLPs) into rat alveolar bone sockets for 8 and 16 weeks, resulting in complete attachment of tooth roots to the surrounding alveolar bone with a periodontal ligament fiber apparatus closely matching physiological controls along the entire root surface. Displacement studies and biochemical analyses confirmed that progenitor-based engineered periodontal tissues were similar to control teeth and

  16. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae

    2015-01-01

    that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

  17. Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber assembly in engineered vascular tissues.

    Science.gov (United States)

    Lin, Shigang; Mequanint, Kibret

    2017-09-01

    In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers. Incorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and

  18. Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    Yanping Zhang

    2018-05-01

    Full Text Available Hair cell (HC loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/β-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5, Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs. Our previous studies showed that Lgr6+ cells are a subpopulation of Lgr5+ progenitor cells and that both Lgr6+ and Lgr5+ progenitors can generate Myosin7a+ HCs in vitro. Thus we hypothesized that Lgr6+ cells are an enriched population of cochlear progenitor cells. However, the detailed distinctions between the Lgr5+ and Lgr6+ progenitors are unclear. Here, we systematically compared the proliferation, HC differentiation, and detailed transcriptome expression profiles of these two progenitor populations. We found that the same number of isolated Lgr6+ progenitors generated significantly more Myosin7a+ HCs compared to Lgr5+ progenitors; however, Lgr5+ progenitors formed more epithelial colonies and more spheres than Lgr6+ progenitors in vitro. Using RNA-Seq, we compared the transcriptome differences between Lgr5+ and Lgr6+ progenitors and identified a list of significantly differential expressed genes that might regulate the proliferation and differentiation of these HC progenitors, including 4 cell cycle genes, 9 cell signaling pathway genes, and 54 transcription factors. In conclusion, we demonstrate that Lgr6+ progenitors are an enriched population of inner ear progenitors that generate more HCs compared to Lgr5+ progenitors in the newborn mouse cochlea, and the our research provides a series of genes that might regulate the proliferation of progenitors

  19. Electroacupuncture Promotes Proliferation of Amplifying Neural Progenitors and Preserves Quiescent Neural Progenitors from Apoptosis to Alleviate Depressive-Like and Anxiety-Like Behaviours

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2014-01-01

    Full Text Available The present study was designed to investigate the effects of electroacupuncture (EA on depressive-like and anxiety-like behaviours and neural progenitors in the hippocampal dentate gyrus (DG in a chronic unpredictable stress (CUS rat model of depression. After being exposed to a CUS procedure for 2 weeks, rats were subjected to EA treatment, which was performed on acupoints Du-20 (Bai-Hui and GB-34 (Yang-Ling-Quan, once every other day for 15 consecutive days (including 8 treatments, with each treatment lasting for 30 min. The behavioural tests (i.e., forced swimming test, elevated plus-maze test, and open-field entries test revealed that EA alleviated the depressive-like and anxiety-like behaviours of the stressed rats. Immunohistochemical results showed that proliferative cells (BrdU-positive in the EA group were significantly larger in number compared with the Model group. Further, the results showed that EA significantly promoted the proliferation of amplifying neural progenitors (ANPs and simultaneously inhibited the apoptosis of quiescent neural progenitors (QNPs. In a word, the mechanism underlying the antidepressant-like effects of EA is associated with enhancement of ANPs proliferation and preserving QNPs from apoptosis.

  20. THE YELLOW SUPERGIANT PROGENITOR OF THE TYPE II SUPERNOVA 2011dh IN M51

    International Nuclear Information System (INIS)

    Maund, J. R.; Fraser, M.; Smartt, S. J.; Kotak, R.; Magill, L.; Ergon, M.; Sollerman, J.; Pastorello, A.; Benetti, S.; Botticella, M.-T.; Valenti, S.; Bufano, F.; Danziger, I. J.; Stephens, A. W.

    2011-01-01

    We present the detection of the putative progenitor of the Type IIb SN 2011dh in archival pre-explosion Hubble Space Telescope images. Using post-explosion Adaptive Optics imaging with Gemini NIRI+ALTAIR, the position of the supernova (SN) in the pre-explosion images was determined to within 23 mas. The progenitor candidate is consistent with an F8 supergiant star (logL/L sun = 4.92 ± 0.20 and T eff = 6000 ± 280 K). Through comparison with stellar evolution tracks, this corresponds to a single star at the end of core C-burning with an initial mass of M ZAMS = 13 ± 3 M sun . The possibility of the progenitor source being a cluster is rejected, on the basis of: (1) the source not being spatially extended, (2) the absence of excess Hα emission, and (3) the poor fit to synthetic cluster spectral energy distributions (SEDs). It is unclear if a binary companion is contributing to the observed SED, although given the excellent correspondence of the observed photometry to a single star SED we suggest that the companion does not contribute significantly. Early photometric and spectroscopic observations show fast evolution similar to the transitional Type IIb SN 2008ax and suggest that a large amount of the progenitor's hydrogen envelope was removed before explosion. Late-time observations will reveal if the yellow supergiant or the putative companion star were responsible for this SN explosion.

  1. Constraints for the progenitor masses of 17 historic core-collapse supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Benjamin F.; Peterson, Skyler; Gilbert, Karoline; Dalcanton, Julianne J. [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Murphy, Jeremiah [Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Dolphin, Andrew E. [Raytheon, 1151 E. Hermans Road, Tucson, AZ 85706 (United States); Jennings, Zachary G., E-mail: ben@astro.washington.edu, E-mail: peters8@uw.edu, E-mail: jd@astro.washington.edu, E-mail: jeremiah@physics.fsu.edu, E-mail: kgilbert@stsci.edu, E-mail: dolphin@raytheon.com, E-mail: zgjennin@ucsc.edu [University of California Observatories, Santa Cruz, CA 95064 (United States)

    2014-08-20

    Using resolved stellar photometry measured from archival Hubble Space Telescope imaging, we generate color-magnitude diagrams of the stars within 50 pc of the locations of historic core-collapse supernovae (SNe) that took place in galaxies within 8 Mpc. We fit these color-magnitude distributions with stellar evolution models to determine the best-fit age distribution of the young population. We then translate these age distributions into probability distributions for the progenitor mass of each SN. The measurements are anchored by the main-sequence stars surrounding the event, making them less sensitive to assumptions about binarity, post-main-sequence evolution, or circumstellar dust. We demonstrate that, in cases where the literature contains masses that have been measured from direct imaging, our measurements are consistent with (but less precise than) these measurements. Using this technique, we constrain the progenitor masses of 17 historic SNe, 11 of which have no previous estimates from direct imaging. Our measurements still allow the possibility that all SN progenitor masses are <20 M {sub ☉}. However, the large uncertainties for the highest-mass progenitors also allow the possibility of no upper-mass cutoff.

  2. Directed differentiation of porcine epiblast-derived neural progenitor cells into neurons and glia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel Aabech; Hall, Vanessa Jane; Carter, T.F.

    2011-01-01

    Neural progenitor cells (NPCs) are promising candidates for cell-based therapy of neurodegenerative diseases; however, safety concerns must be addressed through transplantation studies in large animal models, such as the pig. The aim of this study was to derive NPCs from porcine blastocysts...

  3. Repair of Tissues by Adult Stem/Progenitor Cells (MSCs): Controversies, Myths, and Changing Paradigms

    OpenAIRE

    Prockop, Darwin J

    2009-01-01

    Research on stem cells has progressed at a rapid pace and, as might be anticipated, the results have generated several controversies, a few myths and a change in a major paradigm. Some of these issues will be reviewed in this study with special emphasis on how they can be applied to the adult stem/progenitor cells from bone marrow, referred to as MSCs.

  4. Opportunities and Challenges for Repair of Macrovascular Disease using Circulating Blood-Derived Progenitor Cells

    OpenAIRE

    Loeken, Mary R.

    2014-01-01

    There are currently few solutions for diabetic vascular disease that involve repair of damaged tissues. The manuscript by Porat, et al., suggests a possible method to use a patient’s own circulating blood cells to provide progenitors to repair damaged vascular tissues.

  5. Selecting ultra-faint dwarf candidate progenitors in cosmological N-body simulations at high redshifts

    Science.gov (United States)

    Safarzadeh, Mohammadtaher; Ji, Alexander P.; Dooley, Gregory A.; Frebel, Anna; Scannapieco, Evan; Gómez, Facundo A.; O'Shea, Brian W.

    2018-06-01

    The smallest satellites of the Milky Way ceased forming stars during the epoch of reionization and thus provide archaeological access to galaxy formation at z > 6. Numerical studies of these ultrafaint dwarf galaxies (UFDs) require expensive cosmological simulations with high mass resolution that are carried out down to z = 0. However, if we are able to statistically identify UFD host progenitors at high redshifts with relatively high probabilities, we can avoid this high computational cost. To find such candidates, we analyse the merger trees of Milky Way type haloes from the high-resolution Caterpillar suite of dark matter only simulations. Satellite UFD hosts at z = 0 are identified based on four different abundance matching (AM) techniques. All the haloes at high redshifts are traced forward in time in order to compute the probability of surviving as satellite UFDs today. Our results show that selecting potential UFD progenitors based solely on their mass at z = 12 (8) results in a 10 per cent (20 per cent) chance of obtaining a surviving UFD at z = 0 in three of the AM techniques we adopted. We find that the progenitors of surviving satellite UFDs have lower virial ratios (η), and are preferentially located at large distances from the main MW progenitor, while they show no correlation with concentration parameter. Haloes with favorable locations and virial ratios are ≈3 times more likely to survive as satellite UFD candidates at z = 0.

  6. ATP Binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J.E.; Roskams, T.A.D.; Geuken, M.; Havinga, R.; Splinter, P.L.; Petersen, B.E.; LaRusso, N.F.; Kolk, van der D.M.; Kuipers, F.; Faber, K.N.; Müller, M.R.; Jansen, P.L.M.

    2003-01-01

    Background and aim: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  7. ATP binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J. E.; Roskams, T. A. D.; Geuken, M.; Havinga, R.; Splinter, P. L.; Petersen, B. E.; LaRusso, N. F.; van der Kolk, D. M.; Kuipers, F.; Faber, K. N.; Müller, M.; Jansen, P. L. M.

    2003-01-01

    BACKGROUND AND AIM: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  8. ATP binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J.E.; Roskams, TAD; Geuken, M; Havinga, R; Splinter, PL; Petersen, BE; LaRusso, NF; van der Kolk, D.M.; Kuipers, F; Faber, KN; Muller, M; Jansen, PLM

    Background and aim: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  9. Effects of Electromagnetic Radiation from Smartphones on Learning Ability and Hippocampal Progenitor Cell Proliferation in Mice.

    Science.gov (United States)

    Choi, Yu-Jin; Choi, Yun-Sik

    2016-02-01

    Nonionizing radiation is emitted from electronic devices, such as smartphones. In this study, we intended to elucidate the effect of electromagnetic radiation from smartphones on spatial working memory and progenitor cell proliferation in the hippocampus. Both male and female mice were randomly separated into two groups (radiated and control) and the radiated group was exposed to electromagnetic radiation for 9 weeks and 11 weeks for male and female mice, respectively. Spatial working memory was examined with a Y maze, and proliferation of hippocampal progenitor cells were examined by 5-bromo-2'-deoxyuridine administration and immunohistochemical detection. When spatial working memory on a Y maze was examined in the 9(th) week, there was no significant difference in the spontaneous alternation score on the Y maze between the two groups. In addition, there was no significant difference in hippocampal progenitor cell proliferation. However, immunoreactivity to glial fibrillary acidic protein was increased in exposed animals. Next, to test the effect of recovery following chronic radiation exposure, the remaining female mice were further exposed to electromagnetic radiation for 2 more weeks (total 11 weeks), and spontaneous alternation was tested 4 weeks later. In this experiment, although there was no significant difference in the spontaneous alternation scores, the number of arm entry was significantly increased. These data indicate that although chronic electromagnetic radiation does not affect spatial working memory and hippocampal progenitor cell proliferation it can mediate astrocyte activation in the hippocampus and delayed hyperactivity-like behavior.

  10. Expression of cytochrome P450 genes in CD34(+) hematopoietic stem and progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Souček, P.; Anzenbacher, P.; Skoumalová, I.; Dvořák, Michal

    2005-01-01

    Roč. 23, č. 9 (2005), s. 1417-1422 ISSN 1066-5099 Institutional research plan: CEZ:AV0Z50520514 Keywords : CD34+ stem/progenitor cells * cytochrome P450 isoforms Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.094, year: 2005

  11. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke

    2011-01-01

    To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal ve...

  12. [Culture of pancreatic progenitor cells in hanging drop and on floating filter].

    Science.gov (United States)

    Ma, Feng-xia; Chen, Fang; Chi, Ying; Yang, Shao-guang; Lu, Shi-hong; Han, Zhong-chao

    2013-06-01

    To construct a method to culture pancreatic progenitor cells in hanging drop and on floating filter,and to examine if pancreatic progenitor cells can differentiate into mature endocrine cells with this method. Murine embryos at day 12.5 were isolated and digested into single cells,which were then cultured in hanging drop for 24h and formed spheres.Spheres were cultured on the filter for 6 days,which floated in the dish containing medium.During culture,the expressions of pancreas duodenum homeobox-1(PDX-1)and neurogenin3(Ngn3)were determined.The expressions of endocrine and exocrine markers,insulin,glucagon,and carboxypeptidase(CPA)were determined on day 7 by immunohistochemistry.Insulin secretion of spheres stimulated by glucose was detected by ELISA.The changes of pancreatic marker expressions during culture were monitored by real-time polymerase chain reaction(PCR). One day after the culture,there were still a large amount of PDX-1 positive cells in pancreatic spheres,and these cells proliferated.On day 3,high expression of Ngn3 was detected,and the Ngn3-positive cells did not proliferate.On day 7,The expressions of endocrine and exocrine markers in the differentiated pancreatic progenitor cells were detected,which were consistent with that in vivo.Insulin was secreted by spheres upon the stimulation of glucose. In hanging drop and on floating filter,pancreatic progenitor cells can differentiate into mature endocrine cells.

  13. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  14. Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro

    NARCIS (Netherlands)

    de Groot, Martje W G D M; Dingemans, Milou M L; Rus, Katinka H; de Groot, Aart; Westerink, Remco H S

    In vitro methods for developmental neurotoxicity (DNT) testing have the potential to reduce animal use and increase insight into cellular and molecular mechanisms underlying chemical-induced alterations in the development of functional neuronal networks. Mouse neural progenitor cells (mNPCs)

  15. FGF8 activates proliferation and migration in mouse post-natal oligodendrocyte progenitor cells.

    Directory of Open Access Journals (Sweden)

    Pablo Cruz-Martinez

    Full Text Available Fibroblast growth factor 8 (FGF8 is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis. In vitro, oligodendrocyte progenitor cells were cultured with differentiating medium and in the presence of FGF8. Differentiation and proliferation studies were performed by immunocytochemistry and PCR. Also, migration studies were performed in matrigel cultures, where oligodendrocyte progenitor cells were placed at a certain distance of a FGF8-soaked heparin bead. The results showed that both migration and proliferation was induced by FGF8. Furthermore, a similar effect was observed in an in vivo demyelinating mouse model, where oligodendrocyte progenitor cells were observed migrating towards the FGF8-soaked heparin beads where they were grafted. In conclusion, the results shown here demonstrate that FGF8 is a novel factor to induce oligodendrocyte progenitor cell activation, migration and proliferation in vitro, which can be extrapolated in vivo in demyelinated animal models.

  16. Upper limits on the luminosity of the progenitor of type Ia supernova SN2014J

    DEFF Research Database (Denmark)

    Nielsen, M. T. B.; Gilfanov, M.; Bogdan, A.

    2014-01-01

    We analysed archival data of Chandra pre-explosion observations of the position of SN2014J in M82. No X-ray source at this position was detected in the data, and we calculated upper limits on the luminosities of the progenitor. These upper limits allow us to firmly rule out an unobscured supersof...

  17. Constraints for the progenitor masses of 17 historic core-collapse supernovae

    International Nuclear Information System (INIS)

    Williams, Benjamin F.; Peterson, Skyler; Gilbert, Karoline; Dalcanton, Julianne J.; Murphy, Jeremiah; Dolphin, Andrew E.; Jennings, Zachary G.

    2014-01-01

    Using resolved stellar photometry measured from archival Hubble Space Telescope imaging, we generate color-magnitude diagrams of the stars within 50 pc of the locations of historic core-collapse supernovae (SNe) that took place in galaxies within 8 Mpc. We fit these color-magnitude distributions with stellar evolution models to determine the best-fit age distribution of the young population. We then translate these age distributions into probability distributions for the progenitor mass of each SN. The measurements are anchored by the main-sequence stars surrounding the event, making them less sensitive to assumptions about binarity, post-main-sequence evolution, or circumstellar dust. We demonstrate that, in cases where the literature contains masses that have been measured from direct imaging, our measurements are consistent with (but less precise than) these measurements. Using this technique, we constrain the progenitor masses of 17 historic SNe, 11 of which have no previous estimates from direct imaging. Our measurements still allow the possibility that all SN progenitor masses are <20 M ☉ . However, the large uncertainties for the highest-mass progenitors also allow the possibility of no upper-mass cutoff.

  18. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

    NARCIS (Netherlands)

    Krenning, Guido; Dankers, Patricia Y. W.; Drouven, Johannes W.; Waanders, Femke; Franssen, Casper F. M.; van Luyn, Marja J. A.; Harmsen, Martin C.; Popa, Eliane R.

    Krenning G, Dankers PY, Drouven JW, Waanders F, Franssen CF, van Luyn MJ, Harmsen MC, Popa ER. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease. Am J Physiol Renal Physiol 296: F1314-F1322, 2009. First published April 1, 2009; doi:

  19. DYRK1A is a regulator of S phase entry in hepatic progenitor cells

    NARCIS (Netherlands)

    Kruitwagen, Hedwig Suzanne; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda Jm; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

    Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage HPC proliferation is triggered by external activation mechanisms from their niche. Although several important

  20. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

    Science.gov (United States)

    Doulatov, Sergei; Vo, Linda T.; Macari, Elizabeth R.; Wahlster, Lara; Kinney, Melissa A.; Taylor, Alison M.; Barragan, Jessica; Gupta, Manav; McGrath, Katherine; Lee, Hsiang-Ying; Humphries, Jessica M.; DeVine, Alex; Narla, Anupama; Alter, Blanche P.; Beggs, Alan H.; Agarwal, Suneet; Ebert, Benjamin L.; Gazda, Hanna T.; Lodish, Harvey F.; Sieff, Colin A.; Schlaeger, Thorsten M.; Zon, Leonard I.; Daley, George Q.

    2017-01-01

    Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA. PMID:28179501

  1. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  2. A Comparative Study on SN II Progenitors for the Synthesis of Li and ...

    Indian Academy of Sciences (India)

    these two elements for SN II progenitors with 8, 10 and 20 solar masses. The process considered ... explain their origin. Interaction of ... universe expansion rate either due to cosmological term or due to increased 'grav- itational constant' ..... elevate Li production or to suppress B production in early solar system events. The.

  3. Development of MAPC derived induced endodermal progenitors : Generation of pancreatic beta cells and hepatocytes

    NARCIS (Netherlands)

    Sambathkumar, Rangarajan

    2017-01-01

    Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14

  4. Wnt signaling induces differentiation of progenitor cells in organotypic keratinocyte cultures

    Directory of Open Access Journals (Sweden)

    Liu Bob Y

    2007-02-01

    Full Text Available Abstract Background Interfollicular skin develops normally only when the activity of the progenitor cells in the basal layer is counterbalanced by the exit of cells into the suprabasal layers, where they differentiate and cornify to establish barrier function. Distinct stem and progenitor compartments have been demonstrated in hair follicles and sebaceous glands, but there are few data to describe the control of interfollicular progenitor cell activity. Wnt signaling has been shown to be an important growth-inducer of stem cell compartments in skin and many other tissues. Results Here, we test the effect of ectopic Wnt1 expression on the behavior of interfollicular progenitor cells in an organotypic culture model, and find that Wnt1 signaling inhibits their growth and promotes terminal differentiation. Conclusion These results are consistent with the phenotypes reported for transgenic mice engineered to have gain or loss of function of Wnt signaling in skin, which would recommend our culture model as an accurate one for molecular analysis. Since it is known that canonical ligands are expressed in skin, it is likely that this pathway normally regulates the balance of growth and differentiation, and suggests it could be important to pathogenesis.

  5. Meis1 regulates Foxn4 expression during retinal progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Mohammed M. Islam

    2013-09-01

    The transcription factor forkhead box N4 (Foxn4 is a key regulator in a variety of biological processes during development. In particular, Foxn4 plays an essential role in the genesis of horizontal and amacrine neurons from neural progenitors in the vertebrate retina. Although the functions of Foxn4 have been well established, the transcriptional regulation of Foxn4 expression during progenitor cell differentiation remains unclear. Here, we report that an evolutionarily conserved 129 bp noncoding DNA fragment (Foxn4CR4.2 or CR4.2, located ∼26 kb upstream of Foxn4 transcription start site, functions as a cis-element for Foxn4 regulation. CR4.2 directs gene expression in Foxn4-positive cells, primarily in progenitors, differentiating horizontal and amacrine cells. We further determined that the gene regulatory activity of CR4.2 is modulated by Meis1 binding motif, which is bound and activated by Meis1 transcription factor. Deletion of the Meis1 binding motif or knockdown of Meis1 expression abolishes the gene regulatory activity of CR4.2. In addition, knockdown of Meis1 expression diminishes the endogenous Foxn4 expression and affects cell lineage development. Together, we demonstrate that CR4.2 and its interacting Meis1 transcription factor play important roles in regulating Foxn4 expression during early retinogenesis. These findings provide new insights into molecular mechanisms that govern gene regulation in retinal progenitors and specific cell lineage development.

  6. Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects.

    Science.gov (United States)

    Mikirova, Nina A; Jackson, James A; Hunninghake, Ron; Kenyon, Julian; Chan, Kyle W H; Swindlehurst, Cathy A; Minev, Boris; Patel, Amit N; Murphy, Michael P; Smith, Leonard; Ramos, Famela; Ichim, Thomas E; Riordan, Neil H

    2010-04-08

    The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

  7. A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance

    DEFF Research Database (Denmark)

    Livigni, Alessandra; Peradziryi, Hanna; Sharov, Alexei A

    2013-01-01

    BACKGROUND: The class V POU domain transcription factor Oct4 (Pou5f1) is a pivotal regulator of embryonic stem cell (ESC) self-renewal and reprogramming of somatic cells to induced pluripotent stem (iPS) cells. Oct4 is also an important evolutionarily conserved regulator of progenitor cell differ...

  8. LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.

    Science.gov (United States)

    McKey, Jennifer; Martire, Delphine; de Santa Barbara, Pascal; Faure, Sandrine

    2016-04-28

    Smooth muscle cell (SMC) plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions. Here, we show that Limb Expression 1 (LIX1) molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. We show that LIX1 is required for stomach SMC determination to regulate the expression of the pro-proliferative gene YAP1 and mesenchymal cell proliferation. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP1 activity. We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation. Our data highlight dual roles for LIX1 and YAP1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs.

  9. MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors

    NARCIS (Netherlands)

    Giacomazzi, G. (Giorgia); Holvoet, B. (Bryan); Trenson, S. (Sander); Caluwé, E. (Ellen); Kravic, B. (Bojana); Grosemans, H. (Hanne); Cortés-Calabuig, Á. (Álvaro); Deroose, C.M. (Christophe M.); D. Huylebroeck (Danny); Hashemolhosseini, S. (Said); S. Janssens (Stefan); McNally, E. (Elizabeth); Quattrocelli, M. (Mattia); Sampaolesi, M. (Maurilio)

    2017-01-01

    textabstractMuscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types

  10. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  11. Epithelial progenitor cell lines as models of normal breast morphogenesis and neoplasia

    DEFF Research Database (Denmark)

    Petersen, Ole William; Gudjonsson, Thorarinn; Villadsen, René

    2003-01-01

    The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial compartment. This has been subdivided recently into at least three luminal subtypes based on gene expression patterns. The value of kn...

  12. Global transcriptome analysis of T-competent progenitors in the bone marrow

    Directory of Open Access Journals (Sweden)

    Vionnie W.C. Yu

    2015-09-01

    Full Text Available T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015 [1]. Selective endogenous depletion of Ocn+ cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR led to reduction of T-competent common lymphoid progenitors (Ly6D− CLPs in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn+ cells in the bone marrow ensures the production of Ly6D− CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D− CLPs derived from Ocn+ cells deleted mice (OcnCre+;iDTR compared to those derived from control littermates (OcnCre−;iDTR. These data are publically available from NCBI Gene Expression Omnibus (GEO with the accession number GSE66102.

  13. Stem and Progenitor Cell-Based Therapy of the Central Nervous System

    DEFF Research Database (Denmark)

    Goldman, Steven A.

    2016-01-01

    A variety of neurological disorders are attractive targets for stem and progenitor cell-based therapy. Yet many conditions are not, whether by virtue of an inhospitable disease environment, poorly understood pathophysiology, or poor alignment of donor cell capabilities with patient needs. Moreove...

  14. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke

    2011-01-01

    To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal ve...... that modulation of host immunity is likely necessary for prolonged xenograft survival in this model....

  15. MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

    Directory of Open Access Journals (Sweden)

    Francisca F. Vasconcelos

    2016-10-01

    Full Text Available The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

  16. Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects

    Directory of Open Access Journals (Sweden)

    Minev Boris

    2010-04-01

    Full Text Available Abstract The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

  17. Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors

    NARCIS (Netherlands)

    van den Akker, Emile; van Dijk, Thamar; Parren-van Amelsvoort, Martine; Grossmann, Katja S.; Schaeper, Ute; Toney-Earley, Kenya; Waltz, Susan E.; Löwenberg, Bob; von Lindern, Marieke

    2004-01-01

    Erythropoietin (EPO) is required for cell survival during differentiation and for progenitor expansion during stress erythropoiesis. Although signaling pathways may couple directly to docking sites on the EPO receptor (EpoR), additional docking molecules expand the signaling platform of the

  18. In vitro effects of Epidiferphane™ on adult human neural progenitor cells

    Science.gov (United States)

    Neural stem cells have the capacity to respond to their environment, migrate to the injury site and generate functional cell types, and thus they hold great promise for cell therapies. In addition to representing a source for central nervous system (CNS) repair, neural stem and progenitor cells als...

  19. Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

    DEFF Research Database (Denmark)

    Golonzhka, Olga; Nord, Alex; Tang, Paul L F

    2015-01-01

    We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient...

  20. PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

    Science.gov (United States)

    Zhu, Guo; Rankin, Sherri L; Larson, Jon D; Zhu, Xiaoyan; Chow, Lionel M L; Qu, Chunxu; Zhang, Jinghui; Ellison, David W; Baker, Suzanne J

    2017-01-01

    Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR. ©2016 American Association for Cancer Research.