Inaba, Mayu; Venkei, Zsolt G; Yamashita, Yukiko M
2015-03-20
Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD.
Asymmetric cell division during T cell development controls downstream fate
Pham, Kim; Shimoni, Raz; Charnley, Mirren; Ludford-Menting, Mandy J.; Hawkins, Edwin D.; Ramsbottom, Kelly; Oliaro, Jane; Izon, David; Ting, Stephen B.; Reynolds, Joseph; Lythe, Grant; Molina-Paris, Carmen; Melichar, Heather; Robey, Ellen; Humbert, Patrick O.; Gu, Min
2015-01-01
During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the β-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the β-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal. PMID:26370500
Charruyer, Alexandra; Fong, Stephen; Vitcov, Giselle G; Sklar, Samuel; Tabernik, Leah; Taneja, Monica; Caputo, Melinda; Soeung, Catherine; Yue, Lili; Uchida, Yoshi; Arron, Sarah T; Horton, Karen M; Foster, Robert D; Sano, Shigetoshi; North, Jeffrey P; Ghadially, Ruby
2017-08-01
The balance between asymmetric and symmetric stem cell (SC) divisions is key to tissue homeostasis, and dysregulation of this balance has been shown in cancers. We hypothesized that the balance between asymmetric cell divisions (ACDs) and symmetric cell divisions (SCDs) would be dysregulated in the benign hyperproliferation of psoriasis. We found that, while SCDs were increased in squamous cell carcinoma (SCC) (human and murine), ACDs were increased in the benign hyperproliferation of psoriasis (human and murine). Furthermore, while sonic hedgehog (linked to human cancer) and pifithrinα (p53 inhibitor) promoted SCDs, interleukin (IL)-1α and amphiregulin (associated with benign epidermal hyperproliferation) promoted ACDs. While there was dysregulation of the ACD:SCD ratio, no change in SC frequency was detected in epidermis from psoriasis patients, or in human keratinocytes treated with IL-1α or amphiregulin. We investigated the mechanism whereby immune alterations of psoriasis result in ACDs. IL17 inhibitors are effective new therapies for psoriasis. We found that IL17A increased ACDs in human keratinocytes. Additionally, studies in the imiquimod-induced psoriasis-like mouse model revealed that ACDs in psoriasis are IL17A-dependent. In summary, our studies suggest an association between benign hyperproliferation and increased ACDs. This work begins to elucidate the mechanisms by which immune alteration can induce keratinocyte hyperproliferation. Altogether, this work affirms that a finely tuned balance of ACDs and SCDs is important and that manipulating this balance may constitute an effective treatment strategy for hyperproliferative diseases. Stem Cells 2017;35:2001-2007. © 2017 AlphaMed Press.
Symmetry breaking in human neuroblastoma cells
Izumi, Hideki; Kaneko, Yasuhiko
2014-01-01
Asymmetric cell division (ACD) is a characteristic of cancer stem cells, which exhibit high malignant potential. However, the cellular mechanisms that regulate symmetric (self-renewal) and asymmetric cell divisions are mostly unknown. Using human neuroblastoma cells, we found that the oncosuppressor protein tripartite motif containing 32 (TRIM32) positively regulates ACD. PMID:27308367
Robust control of mitotic spindle orientation in the developing epidermis
Poulson, Nicholas D.
2010-01-01
Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this study, we show that individual epidermal cells can undergo both types of division, and therefore, the balance is provided by the sum of individual cells’ choices. In addition, we define two control points for determining a cell’s mode of division. First is the expression of the mouse Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD). However, there is robust control of division orientation as excessive ACDs are prevented by a change in the localization of NuMA, an effector of spindle orientation. Finally, we show that p63, a transcriptional regulator of stratification, does not control either of these processes. These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice. PMID:21098114
Wölwer, Christina B.; Gödde, Nathan; Pase, Luke B.; Elsum, Imogen A.; Lim, Krystle Y. B.; Sacirbegovic, Faruk; Walkley, Carl R.; Ellis, Sarah; Ohno, Shigeo; Matsuzaki, Fumio; Russell, Sarah M.; Humbert, Patrick O.
2017-01-01
Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Here we investigated gene expression of members of the Par, Scribble and Pins/Gpsm2 asymmetric cell division complexes in erythroid cells, and functionally tested their role in erythroid enucleation in vivo and ex vivo. Despite their roles in regulating ACD in other contexts, we found that these polarity regulators are not essential for erythroid enucleation, nor for erythroid development in vivo. Together our results put into question a role for cell polarity and asymmetric cell division in erythroid enucleation. PMID:28095473
Ting, Stephen B; Deneault, Eric; Hope, Kristin; Cellot, Sonia; Chagraoui, Jalila; Mayotte, Nadine; Dorn, Jonas F; Laverdure, Jean-Philippe; Harvey, Michael; Hawkins, Edwin D; Russell, Sarah M; Maddox, Paul S; Iscove, Norman N; Sauvageau, Guy
2012-03-15
The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vorhagen, Susanne; Niessen, Carien M., E-mail: carien.niessen@uni-koeln.de
2014-11-01
Oriented cell division is a key regulator of tissue architecture and crucial for morphogenesis and homeostasis. Balanced regulation of proliferation and differentiation is an essential property of tissues not only to drive morphogenesis but also to maintain and restore homeostasis. In many tissues orientation of cell division is coupled to the regulation of differentiation producing daughters with similar (symmetric cell division, SCD) or differential fate (asymmetric cell division, ACD). This allows the organism to generate cell lineage diversity from a small pool of stem and progenitor cells. Division orientation and/or the ratio of ACD/SCD need to be tightly controlled. Lossmore » of orientation or an altered ratio can promote overgrowth, alter tissue architecture and induce aberrant differentiation, and have been linked to morphogenetic diseases, cancer and aging. A key requirement for oriented division is the presence of a polarity axis, which can be established through cell intrinsic and/or extrinsic signals. Polarity proteins translate such internal and external cues to drive polarization. In this review we will focus on the role of the polarity complex aPKC/Par3/Par6 in the regulation of division orientation and cell fate in different mammalian epithelia. We will compare the conserved function of this complex in mitotic spindle orientation and distribution of cell fate determinants and highlight common and differential mechanisms in which this complex is used by tissues to adapt division orientation and cell fate to the specific properties of the epithelium.« less
Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak
2012-01-01
Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764
Asymmetric cell division of stem cells in the lung and other systems
Berika, Mohamed; Elgayyar, Marwa E.; El-Hashash, Ahmed H. K.
2014-01-01
New insights have been added to identification, behavior and cellular properties of embryonic and tissue-specific stem cells over the last few years. The modes of stem cell division, asymmetric vs. symmetric, are tightly regulated during development and regeneration. The proper choice of a stem cell to divide asymmetrically or symmetrically has great consequences for development and disease because inappropriate asymmetric division disrupts organ morphogenesis, whereas uncontrolled symmetric division induces tumorigenesis. Therefore, understanding the behavior of lung stem cells could identify innovative solutions for restoring normal morphogenesis and/or regeneration of different organs. In this concise review, we describe recent studies in our laboratory about the mode of division of lung epithelial stem cells. We also compare asymmetric cell division (ACD) in the lung stem cells with other tissues in different organisms. PMID:25364740
Cell cycle in ascidian eggs and embryos.
McDougall, Alex; Chenevert, Janet; Lee, Karen W; Hebras, Celine; Dumollard, Remi
2011-01-01
In ascidians the cell cycle machinery has been studied mainly in oocytes while ascidian embryos have been used to dissect the mechanism that controls asymmetric cell division (ACD). Here we overview the most specific and often exceptional points and events in cell cycle control in ascidian oocytes and early embryos. Mature stage IV eggs are arrested at metaphase I due to cytostatic factor (CSF). In vertebrates, unfertilized eggs are arrested at metaphase II by CSF. Meta II-CSF is mediated by the Mos/MEK/MAPK/Erp1 pathway, which inhibits the ubiquitin ligase APC/C(cdc20) preventing cyclin B destruction thus stabilizing MPF activity. CSF is inactivated by the fertilization Ca(2+) transient that stimulates the destruction of Erp1 thus releasing APC/C(cdc20) from inhibition. Although many of the components of CSF are conserved between the ascidian and the vertebrates, the lack of Erp1 in the ascidians (and indeed other invertebrates) is notable since the Mos/MAPK pathway nonetheless mediates Meta I-CSF. Moreover, since the fertilization Ca(2+) transient targets Erp1, it is not clear how the sperm-triggered Ca(2+) transient in ascidians (and again other invertebrates) stimulates cyclin B destruction in the absence of Erp1. Nonetheless, like mammalian eggs, sperm trigger a series of Ca(2+) oscillations that increases the rate of cyclin B destruction and the subsequent loss of MAPK activity leading to meiotic exit in ascidians. Positive feedback from MPF maintains the Ca(2+) oscillations in fertilized ascidian eggs ensuring the eventual loss of MPF stimulating the egg-to-embryo transition. Embryonic cell cycles in the ascidian are highly stereotyped where both the rate of cell division and the orientation of cell division planes are precisely controlled. Three successive rounds of ACD generate two small posterior germ cell precursors at the 64 cell stage. The centrosome-attracting body (CAB) is a macroscopic cortical structure visible by light microscopy that causes these three rounds of ACD. Entry into mitosis activates the CAB causing the whole mitotic spindle to rotate and migrate toward the cortical CAB leading to a highly ACD whereby one small cell is formed that inherits the CAB and approximately 40 maternal postplasmic/PEM RNAs including the germ cell marker vasa.
Juranić, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanić, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas
2012-01-01
Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle–dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s). PMID:23250449
Arabidopsis ACCELERATED CELL DEATH2 Modulates Programmed Cell DeathW⃞
Yao, Nan; Greenberg, Jean T.
2006-01-01
The Arabidopsis thaliana chloroplast protein ACCELERATED CELL DEATH2 (ACD2) modulates the amount of programmed cell death (PCD) triggered by Pseudomonas syringae and protoporphyrin IX (PPIX) treatment. In vitro, ACD2 can reduce red chlorophyll catabolite, a chlorophyll derivative. We find that ACD2 shields root protoplasts that lack chlorophyll from light- and PPIX-induced PCD. Thus, chlorophyll catabolism is not obligatory for ACD2 anti-PCD function. Upon P. syringae infection, ACD2 levels and localization change in cells undergoing PCD and in their close neighbors. Thus, ACD2 shifts from being largely in chloroplasts to partitioning to chloroplasts, mitochondria, and, to a small extent, cytosol. ACD2 protects cells from PCD that requires the early mitochondrial oxidative burst. Later, the chloroplasts of dying cells generate NO, which only slightly affects cell viability. Finally, the mitochondria in dying cells have dramatically altered movements and cellular distribution. Overproduction of both ACD2 (localized to mitochondria and chloroplasts) and ascorbate peroxidase (localized to chloroplasts) greatly reduces P. syringae–induced PCD, suggesting a pro-PCD role for mitochondrial and chloroplast events. During infection, ACD2 may bind to and/or reduce PCD-inducing porphyrin-related molecules in mitochondria and possibly chloroplasts that generate reactive oxygen species, cause altered organelle behavior, and activate a cascade of PCD-inducing events. PMID:16387834
Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors.
Prodon, François; Chenevert, Janet; Hébras, Céline; Dumollard, Rémi; Faure, Emmanuel; Gonzalez-Garcia, Jose; Nishida, Hiroki; Sardet, Christian; McDougall, Alex
2010-06-01
Mitotic spindle orientation with respect to cortical polarity cues generates molecularly distinct daughter cells during asymmetric cell division (ACD). However, during ACD it remains unknown how the orientation of the mitotic spindle is regulated by cortical polarity cues until furrowing begins. In ascidians, the cortical centrosome-attracting body (CAB) generates three successive unequal cleavages and the asymmetric segregation of 40 localized postplasmic/PEM RNAs in germ cell precursors from the 8-64 cell stage. By combining fast 4D confocal fluorescence imaging with gene-silencing and classical blastomere isolation experiments, we show that spindle repositioning mechanisms are active from prometaphase until anaphase, when furrowing is initiated in B5.2 cells. We show that the vegetal-most spindle pole/centrosome is attracted towards the CAB during prometaphase, causing the spindle to position asymmetrically near the cortex. Next, during anaphase, the opposite spindle pole/centrosome is attracted towards the border with neighbouring B5.1 blastomeres, causing the spindle to rotate (10 degrees /minute) and migrate (3 microm/minute). Dynamic 4D fluorescence imaging of filamentous actin and plasma membrane shows that precise orientation of the cleavage furrow is determined by this second phase of rotational spindle displacement. Furthermore, in pairs of isolated B5.2 blastomeres, the second phase of rotational spindle displacement was lost. Finally, knockdown of PEM1, a protein localized in the CAB and required for unequal cleavage in B5.2 cells, completely randomizes spindle orientation. Together these data show that two separate mechanisms active during mitosis are responsible for spindle positioning, leading to precise orientation of the cleavage furrow during ACD in the cells that give rise to the germ lineage in ascidians.
Shi, Yu-Ling; Gu, Jun; Park, Jun-Yang; Xu, Ying-Ping; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng
2012-01-01
Background Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). Objective The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. Methods ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleens and skin draining lymph nodes were collected for immune staining. Results TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4+ and CD8+ T cells, Foxp3+CD4+ regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Conclusion Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases. PMID:22999682
Davis, Zachary B; Cogswell, Andrew; Scott, Hamish; Mertsching, Amanda; Boucau, Julie; Wambua, Daniel; Le Gall, Sylvie; Planelles, Vicente; Campbell, Kerry S; Barker, Edward
2016-02-01
Major histocompatibility class I (MHC-I)-specific inhibitory receptors on natural killer (NK) cells (iNKRs) tolerize mature NK cell responses toward normal cells. NK cells generate cytolytic responses to virus-infected or malignant target cells with altered or decreased MHC-I surface expression due to the loss of tolerizing ligands. The NKG2A/CD94 iNKR suppresses NK cell responses through recognition of the non-classical MHC-I, HLA-E. We used HIV-infected primary T-cells as targets in an in vitro cytolytic assay with autologous NK cells from healthy donors. In these experiments, primary NKG2A/CD94(+) NK cells surprisingly generated the most efficient responses toward HIV-infected T-cells, despite high HLA-E expression on the infected targets. Since certain MHC-I-presented peptides can alter recognition by iNKRs, we hypothesized that HIV-1-derived peptides presented by HLA-E on infected cells may block engagement with NKG2A/CD94, thereby engendering susceptibility to NKG2A/CD94(+) NK cells. We demonstrate that HLA-E is capable of presenting a highly conserved peptide from HIV-1 capsid (AISPRTLNA) that is not recognized by NKG2A/CD94. We further confirmed that HLA-C expressed on HIV-infected cells restricts attack by KIR2DL(+) CD56(dim) NK cells, in contrast to the efficient responses by CD56(bright) NK cells, which express predominantly NKG2A/CD94 and lack KIR2DLs. These findings are important since the use of NK cells was recently proposed to treat latently HIV-1-infected patients in combination with latency reversing agents. Our results provide a mechanistic basis to guide these future clinical studies, suggesting that ex vivo-expanded NKG2A/CD94(+) KIR2DL(-) NK cells may be uniquely beneficial.
Davis, Zachary B.; Cogswell, Andrew; Scott, Hamish; Mertsching, Amanda; Boucau, Julie; Wambua, Daniel; Le Gall, Sylvie; Planelles, Vicente; Campbell, Kerry S.; Barker, Edward
2016-01-01
Major histocompatibility class I (MHC-I)-specific inhibitory receptors on natural killer (NK) cells (iNKRs) tolerize mature NK cell responses toward normal cells. NK cells generate cytolytic responses to virus-infected or malignant target cells with altered or decreased MHC-I surface expression due to the loss of tolerizing ligands. The NKG2A/CD94 iNKR suppresses NK cell responses through recognition of the non-classical MHC-I, HLA-E. We used HIV-infected primary T-cells as targets in an in vitro cytolytic assay with autologous NK cells from healthy donors. In these experiments, primary NKG2A/CD94+ NK cells surprisingly generated the most efficient responses toward HIV-infected T-cells, despite high HLA-E expression on the infected targets. Since certain MHC-I-presented peptides can alter recognition by iNKRs, we hypothesized that HIV-1-derived peptides presented by HLA-E on infected cells may block engagement with NKG2A/CD94, thereby engendering susceptibility to NKG2A/CD94+ NK cells. We demonstrate that HLA-E is capable of presenting a highly conserved peptide from HIV-1 capsid (AISPRTLNA) that is not recognized by NKG2A/CD94. We further confirmed that HLA-C expressed on HIV-infected cells restricts attack by KIR2DL+ CD56dim NK cells, in contrast to the efficient responses by CD56bright NK cells, which express predominantly NKG2A/CD94 and lack KIR2DLs. These findings are important since the use of NK cells was recently proposed to treat latently HIV-1-infected patients in combination with latency reversing agents. Our results provide a mechanistic basis to guide these future clinical studies, suggesting that ex vivo-expanded NKG2A/CD94+ KIR2DL- NK cells may be uniquely beneficial. PMID:26828202
Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion.
Laws, L H; Parker, C E; Cherala, G; Koguchi, Y; Waisman, A; Slifka, M K; Oberbarnscheidt, M H; Obhrai, J S; Yeung, M Y; Riella, L V
2016-11-01
B cells play a central role in antibody-mediated rejection and certain autoimmune diseases. However, B cell-targeted therapy such as anti-CD20 B cell-depleting antibody (aCD20) has yielded mixed results in improving outcomes. In this study, we investigated whether an accelerated B cell reconstitution leading to aCD20 depletion resistance could account for these discrepancies. Using a transplantation model, we found that antigen-independent inflammation, likely through toll-like receptor (TLR) signaling, was sufficient to mitigate B cell depletion. Secondary lymphoid organs had a quicker recovery of B cells when compared to peripheral blood. Inflammation altered the pharmacokinetics (PK) and pharmacodynamics (PD) of aCD20 therapy by shortening drug half-life and accelerating the reconstitution of the peripheral B cell pool by bone marrow-derived B cell precursors. IVIG (intravenous immunoglobulin) coadministration also shortened aCD20 drug half-life and led to accelerated B cell recovery. Repeated aCD20 dosing restored B cell depletion and delayed allograft rejection, especially B cell-dependent, antibody-independent allograft rejection. These data demonstrate the importance of further clinical studies of the PK/PD of monoclonal antibody treatment in inflammatory conditions. The data also highlight the disconnect between B cell depletion on peripheral blood compared to secondary lymphoid organs, the deleterious effect of IVIG when given with aCD20 and the relevance of redosing of aCD20 for effective B cell depletion in alloimmunity. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.
Loganathan, Praburaman; Myung, Hyun; Muthusamy, Govarthanan; Lee, Kui-Jae; Seralathan, Kamala-Kannan; Oh, Byung-Taek
2015-10-01
This study aimed to understand the influence of heavy metals on 1-aminocyclopropane-1-carboxylate deaminase activity (ACCD) and acdS gene expression in Herbaspirillium sp. GW103. The GW103 strain ACCD activity decreased in cells grown in a medium supplemented with Pb and As, whereas cells grown in medium supplemented with Cu showed increase in enzyme activity. The GW103 strain produced 262.2 ± 6.17 μmol of α-ketobutyrate per milligram of protein per hour during ACC deamination at 25 °C after 24 h incubation. Using a PCR approach, an acdS coding-gene of 1.06 kbp was amplified in isolate GW103, showing 92% identity with Herbaspirillum seropedicae SmR1 acdS gene. Real time quantitative polymerase chain reaction results indicate that the acdS expression rate was increased (7.1-fold) in the presence of Cu, whereas it decreased (0.2- and 0.1-fold) in the presence of As and Pb. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2007-04-13
Yuri's Night at Ames a celebration of the first human in space. Ames Planetary Scientist with the Space Science Division Dr Chris McKay addresses a audience about Mars and life in extreme environments.
2009-12-10
Korean High Level Delegation Visit Ames Certer Director and various Senior staff: John Hines, Ames Center Chief Technologist (middel left) explains operations at the LADEE lab to Soon-Duk Bae, Deputy Director, Big Science Policy Division, Ministry of Educaiton, Science Technology, Young-Mok Hyun, Deputy Director, Space Development Division, Ministry of Educaiton, Science Technology, Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute.
2009-12-10
Korean High Level Delegation Visit Ames Certer Director and various Senior staff: Dan Andrews give presentation about LCROSS/LRO to Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute, Soon-Duk Bae, Deputy Director, Big Science Policy Division, Ministry of Educaiton, Science Technology, Young-Mok Hyun, Deputy Director, Space Development Division, Ministry of Educaiton, Science Technology, Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute.
75 FR 67380 - Office of the Director; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-02
... of Outside Awards for ACD Approval; Biomedical Workforce Issues; ACD Stem Cell Working Group Report...: 8 a.m. to 3 p.m. Agenda: NIH Director's Report, Lasker Clinical Research Program; ACD TRND Working...
Vijay, Srinivasan; Nair, Rashmi Ravindran; Sharan, Deepti; Jakkala, Kishor; Mukkayyan, Nagaraja; Swaminath, Sharmada; Pradhan, Atul; Joshi, Niranjan V.; Ajitkumar, Parthasarathi
2017-01-01
The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (~10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (~90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed from the SCDs of short-sized mother cells and having comparable growth rates, always showed comparable stress-susceptibility. These observations and the presence of M. tuberculosis SCs and NCs in pulmonary tuberculosis patients' sputum earlier reported by us imply a physiological role for the SCs and the NCs under the stress conditions. The plausible reasons for the higher stress susceptibility of SCs and lower stress susceptibility of NCs are discussed. PMID:28377757
2010-06-03
NASA Headquarter's Office of Infrastructure and Administration, Environmental Management Division presents the annual Blue Marble Award to Ames Scientist Leslie Prufert-Bebout receives . Leslie Prufert-Bebout is a microbial ecologist who studies many different species of algea in natural biological communities.
2010-06-03
NASA Headquarter's Office of Infrastructure and Administration, Environmental Management Division presents the annual Blue Marble Award to Ames Scientist Leslie Prufert-Bebout receives . Leslie Prufert-Bebout is a microbial ecologist who studies many different species of algea in natural biological communities.
2009-12-10
Korean High Level Delegation Visit Ames Certer Director and various Senior staff: John Hines, Ames Center Chief Technologist (middel left) explains PharmaSat (small Satellites) to Soon-Duk Bae, Deputy Director, Big Science Policy Division, Ministry of Educaiton, Science Technology, Young-Mok Hyun, Deputy Director, Space Development Division, Ministry of Educaiton, Science Technology, Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute. Unkonw person at the end of table.
2008-07-14
California Governor Arnold Schwarzenegger during a press briefing following a visit to Ames Earth Science Division for a briefing by Steve Hipskind on NASA Ames remote sensing fire fighting efforts. Also shown left to right, Mike Freilich, Director, NASA Earth Sceinces Division, Steve Hipskind, Pete Worden, Governor Schwarzenegger, Chief Del Walters, Assistant Region Fire Chief, California Department of Forestry and Fire Protection, Tom Maruyama, Deputy Director, Office of Emergency Services
Expression of neuropeptides and their degrading enzymes in ACD.
Bak, H; Lee, W J; Lee, Y W; Chang, S-E; Choi, J-H; Kim, M N; Kim, B J; Choi, Y S; Suh, H S
2010-04-01
Sensory neuropeptides such as neurokinin A or substance P modulate skin and immune cells the functions of neurokinin receptor activation during neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of these neuropeptide mediators, which are released from sensory nerves, immune and skin cells during cutaneous responses to endogenous or exogenous noxious stimuli. Recently, studies have suggested that neuropeptides are one of the major pathogenetic fact in many dermatoses, such as allergic contact dermatitis (ACD), atopic dermatitis and psoriasis. To investigate the expression of major neuropeptides, SP and its degrading enzymes such as NEP and ACE, in the lesions of ACD. A skin biopsy was obtained from 10 patients with ACD. We analysed the expression of these molecules by immunohistochemical staining, confocal laser scanning microscopy, western blotting and reverse transcription PCR. There was a significant increase in expression of SP in keratinocytes from ACD lesions compared with those in control skin. There was also increased expression of ACE but not NEP in ACD. Neuropeptides and their degrading enzymes, particularly SP and ACE, have a significant role in the pathogenesis of ACD.
Xu, Xiaoyun; Xiao, Wei; Zhang, Zhe; Pan, Jianhao; Yan, Yixi; Zhu, Tao; Tang, Dan; Ye, Kaihe; Paranjpe, Manish; Qu, Lintao; Nie, Hong
2018-05-31
Allergic contact dermatitis (ACD) is a highly prevalent inflammatory disease of the skin. As a result of the complex etiology in ACD, therapeutic compounds targeting refractory pruritus in ACD lack efficacy and lead to numerous side effects. In this study, we investigated the anti-pruritic effects of oxymatrine (OMT) and explored its mechanism of action in a mouse model of ACD. 72 male SPF C57BL/6 mice were randomly divided into control group, ACD model group, dexamethasone positive control group (0.08 mg kg -1 ) and 3 OMT groups (80, 40, 20 mg kg -1 ). OMT was administrated by intraperitoneal injection 1 h before video recording on day 10, 24 h after 2nd challenge with SADBE. Cheek skin fold thickness was measured before treatment and after recording. H&E staining was used for pathological observation. RT-qPCR, Immunohistochemistry and LEGENDplexTM assay were used to detect cytokines levels. The population of Treg cells in peripheral blood were detected via flow cytometry. OMT treatment significantly decreases the skin inflammation and scratching bouts. It rescues defects in epidermal keratinization and inflammatory cell infiltration in ACD mice. Administration of OMT significantly reduced levels of IFN-γ, IL-13, IL-17A, TNF-α, IL-22 and mRNA expression of TNF-α and IL-1β. Furthermore, it increased the percentage of Treg cells in peripheral blood of ACD mice. We have demonstrated that OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators. OMT might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD. Copyright © 2018. Published by Elsevier B.V.
KOHLER, ERIN E.; BARUAH, JUGAJYOTI; URAO, NORIFUMI; USHIO-FUKAI, MASUKO; FUKAI, TOHRU; CHATTERJEE, ISHITA; WARY, KISHORE K.
2014-01-01
Endothelial cell (EC) dedifferentiation in relation to neovascularization is a poorly understood process. In this report we addressed the role of Wnt signaling in the mechanisms of neovascularization in adult tissues. Here, we show that a low-dose of 6-bromoindirubin-3′-oxime (BIO), a competitive inhibitor of Glycogen Synthase Kinase (GSK)-3β, induced the stabilization of β-catenin and its subsequent direct interaction with the transcription factor NANOG in the nucleus of ECs. This event induced loss of VE-cadherin from the adherens junctions, increased EC proliferation accompanied by asymmetric cell division (ACD), and formed cellular aggregates in a hanging drop assays indicating the acquisition of a dedifferentiated state. In a chromatin immunoprecipitation assay, nuclear NANOG protein bound to the NANOG- and VEGFR2-promoters in ECs, and the addition of BIO activated the NANOG-promoter-luciferase reporter system in a cell-based assay. Consequently, NANOG-knockdown decreased BIO-induced NOTCH-1 expression, thereby decreasing cell proliferation, ACD and neovascularization. In a Matrigel plug assay, BIO induced increased neovascularization, secondary to the presence of VEGF. Moreover, in a mouse model of hind limb ischemia, BIO augmented neovascularization that was coupled with increased expression of NOTCH-1 in ECs and increased smooth muscle α-actin (SMA)+ cell recruitment around the neovessels. Thus, these results show the ability of a low-dose of BIO to augment neovascularization secondary to VEGF, a process that was accompanied by a partial dedifferentiation of ECs via β-catenin and the NANOG signaling pathway. PMID:24496925
Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald
2009-03-01
Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.
2009-12-10
Korean High Level Delegation Visit Ames Certer Director and various Senior staff: Dan Andrews give presentation about LCROSS/LRO to Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute, Soon-Duk Bae, Deputy Director, Big Science Policy Division, Ministry of Educaiton, Science Technology, Young-Mok Hyun, Deputy Director, Space Development Division, Ministry of Educaiton, Science Technology. Also at table are Chris Giulietti, NASA HQ, John Hines, Ames Center Chief Technologist, Unknow person and Terry Pagaduan, Government Relations/Legislative Affairs office.
2009-12-10
Korean High Level Delegation Visit Ames Certer Director and variou Senior staff: from left to right; Gary Martin, Director of New Ventures and Communication, NASA. Ames, Chris Giulietti, NASA Headquarters, Soon-Duk Bae, Deputy Director, Big Science Policy Division, Ministry of Educaiton, Science Technology, Young-Mok Hyun, Deputy Director, Space Development Division, Ministry of Educaiton, Science Technology, Yvonne Pendleton, Director of Lunar Science Institute, Terry Pagaduan, Ames Government Relations/Legislative Affairs Office, Seorium Lee, Senior Researcher, International Relations Korea Aerospace Research Institute
2001-02-16
New Center Network Deployment ribbon Cutting: from left to right: Maryland Edwards, Code JT upgrade project deputy task manager; Ed Murphy, foundry networks systems engineer; Bohdan Cmaylo, Code JT upgrade project task manager, Scott Santiago, Division Chief, Code JT; Greg Miller, Raytheon Network engineer and Frank Daras, Raytheon network engineering manager.
Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation
Jones, Morgan; Osawa, Gail; Regal, Joshua A.; Weinberg, Daniel N.; Taggart, James; Kocak, Hande; Friedman, Ann; Ferguson, David O.; Keegan, Catherine E.; Maillard, Ivan
2013-01-01
The shelterin complex plays dual functions in telomere homeostasis by recruiting telomerase and preventing the activation of a DNA damage response at telomeric ends. Somatic stem cells require telomerase activity, as evidenced by progressive stem cell loss leading to bone marrow failure in hereditary dyskeratosis congenita. Recent work demonstrates that dyskeratosis congenita can also arise from mutations in specific shelterin genes, although little is known about shelterin functions in somatic stem cells. We found that mouse hematopoietic stem cells (HSCs) are acutely sensitive to inactivation of the shelterin gene Acd, encoding TPP1. Homozygosity for a hypomorphic acd allele preserved the emergence and expansion of fetal HSCs but led to profoundly defective function in transplantation assays. Upon complete Acd inactivation, HSCs expressed p53 target genes, underwent cell cycle arrest, and were severely depleted within days, leading to hematopoietic failure. TPP1 loss induced increased telomeric fusion events in bone marrow progenitors. However, unlike in epidermal stem cells, p53 deficiency did not rescue TPP1-deficient HSCs, indicating that shelterin dysfunction has unique effects in different stem cell populations. Because the consequences of telomere shortening are progressive and unsynchronized, acute loss of shelterin function represents an attractive alternative for studying telomere crisis in hematopoietic progenitors. PMID:24316971
... ACD include: Autoimmune disorders , such as Crohn disease , systemic lupus erythematosus , rheumatoid arthritis , and ulcerative colitis Cancer , ... AOCD; ACD Images Blood cells References Bunn HF. Approach to the anemias. In: Goldman L, Schafer AI, ...
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2012-07-23
... potential to produce allergic contact dermatitis (ACD). NICEATM also requests data generated using in vivo...]m MA, B[ouml]rje A, Luthman, K, Nilsson JLG. 2008. Allergic Contact Dermatitis--Formation... Identification of Contact Allergens: Request for Comments and Data AGENCY: Division of the National Toxicology...
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2011-07-28
... Contact Dermatitis in Humans AGENCY: Division of the National Toxicology Program (DNTP), National... categorizing the potency of substances with the potential to cause allergic contact dermatitis (ACD) as strong... Contact Dermatitis in Humans (NIH Publication No. 11-7709), describes ICCVAM's recommendations for using...
Characterization of antigen-presenting cells from the porcine respiratory system.
López-Robles, Guadalupe; Silva-Campa, Erika; Burgara-Estrella, Alexel; Hernández, Jesús
2015-06-01
Antigen-presenting cells (APCs) are strategically placed in all anatomic sites with high antigen exposure such as the respiratory system. The aim of this study was to evaluate phenotypic and functional properties of APCs from the lung (L-Cs), mediastinal lymph node (LN-Cs) and bronchoalveolar lavage cells (BAL-Cs). The APCs were first analyzed based on forward scatter and side scatter profiles and the selection of MHC-II(high)CD172a(+) cells (referred to as APCs); then the expression of CD1a, CD163, CD206, CD16 and CD11R3 was evaluated in the APCs. The results showed that CD1a, CD163 and CD206 were differentially expressed among L-Cs, LN-Cs and BAL-Cs, suggesting the phenotype MHC-II(high)CD172a(+)CD1a(low/-)CD163(low)CD206(-) for L-Cs and MHC-II(high)CD172a(+)CD1a(+)CD163(low/-)CD206(+) for LN-Cs. BAL-Cs were MHC-II(high)CD172a(+)CD1a(-)CD163(high)CD206(+/-). The functional characteristics of L-Cs and LN-Cs were different from those of BAL-Cs, confirming that L-Cs and LN-Cs resemble specialized APCs. In conclusion, we present the characterization of APCs from L-Cs, LN-Cs and BAL-Cs of the porcine respiratory system. Copyright © 2015 Elsevier Ltd. All rights reserved.
Chemokine Signaling in Allergic Contact Dermatitis: Toward Targeted Therapies.
Smith, Jeffrey S; Rajagopal, Sudarshan; Atwater, Amber Reck
2018-06-22
Allergic contact dermatitis (ACD) is a common skin disease that results in significant cost and morbidity. Despite its high prevalence, therapeutic options are limited. Allergic contact dermatitis is regulated primarily by T cells within the adaptive immune system, but also by natural killer and innate lymphoid cells within the innate immune system. The chemokine receptor system, consisting of chemokine peptides and chemokine G protein-coupled receptors, is a critical regulator of inflammatory processes such as ACD. Specific chemokine signaling pathways are selectively up-regulated in ACD, most prominently CXCR3 and its endogenous chemokines CXCL9, CXCL10, and CXCL11. Recent research demonstrates that these 3 chemokines are not redundant and indeed activate distinct intracellular signaling profiles such as those activated by heterotrimeric G proteins and β-arrestin adapter proteins. Such differential signaling provides an attractive therapeutic target for novel ACD therapies and other inflammatory diseases.
The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice.
de Mayo, Tomas; Conget, Paulette; Becerra-Bayona, Silvia; Sossa, Claudia L; Galvis, Virgilio; Arango-Rodríguez, Martha L
2017-01-01
Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×106 cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8-10 week old female NOD mice. Wound healing was evaluated macroscopically (wound closure) every two days, and microscopically (reepithelialization, dermoepidermal junction, skin appendage regeneration, leukocyte infiltration, vascularization, granulation tissue formation, and density of collagen fibers in the dermis) after 16 days of MSC injection. In addition, we measured growth factors and specific proteins that were present in the allo-acd-mMSCs. Results showed significant differences in the wound healing kinetics of lesions that received allo-acd-mMSCs compared to lesions that received vehicle or allo-mBM-MSCs. In particular, mice treated with allo-acd-mMSCs reached significantly higher percentages of wound closure at day 4, 6 and 8, relative to the allo-mBM-MSCs and vehicle groups (p < 0.05), while wound closure percentages could not be statistically distinguished between the allo-mBM-MSCs and vehicle groups. Also, allo-acd-mMSCs had a greater influence in the skin would healing process. Specifically, they caused a less pronounced inflammatory severe response (p < 0.0001), more granulation tissue formation at an advanced stage (p < 0.0001), and higher density of collagen fibers (p < 0.05) compared to the other groups. Nevertheless, at day 16, both allo-mBM-MSCs and allo-acd-mMSCs revealed a higher effect on the recovery of the quality skin (continuous epidermis; regular dermoepidermal junction and skin appendages) relative to untreated lesions (p < 0.0001), but not between them. On the other hand, ELISA analyses indicated that the allo-acd-mMSCs contained growth factors and proteins relevant to wound healing such as IGF-1, KGF, HGF, VEGF, ANG-2, MMP-1, CoL-1 and PGE2. Compared to allo-acd-mMSCs, the administration of allo-mBM-MSCs is insufficient for wound healing in diabetic mice and delays the therapeutic effect, which maybe explained by the fact that trophic factors secreted by MSCs are critical for skin regeneration, and not the cells per se, suggesting that MSCs may require some time to secrete these factors after their administration.
Li, Weihua; Liu, Fanxiu; Wang, Jun; Long, Man; Wang, Zhigang
2018-03-01
The study aimed to investigate the effect of berberine on allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. Firstly, ACD model was established by sensitizing and challenging with 2,4-dinitrofluorobenzene (DNFB) topically, and the rats were treated with berberine. Ear swelling was assessed, and cytokine, IgE, and histamine productions were measured. The ear biopsies were obtained for histology analysis. Additionally, rat peritoneal mast cells (RPMCs) were isolated for detection of microRNA-21 (miR-21) expression, mitogen-activated protein kinase (MAPK) signaling, and MC degranulation. Lastly, RPMCs were transfected with miR-21 mimic or miR-21 inhibitor to investigate the relationship between miR-21 and p38 pathway in MC. Our results showed that berberine significantly attenuated ear swelling in DNFB-induced ACD (ACD vs high dose of berberine 0.48 ± 0.03 vs. 0.33 ± 0.03 mm, P < 0.01), inhibited inflammatory cell infiltration (86 ± 5.16 vs. 58 ± 4.32 cells/mm 2 , P < 0.01), reduced MC recruitment (61 ± 4.07 vs. 39 ± 3.42 mast cells/mm 2 , P < 0.01), as well as decreased inflammatory cytokine, IgE, and histamine productions (all P < 0.05). Berberine treatment inhibited miR-21 expression, suppressed β-hexosaminidase and histamine release, and prevented p38 phosphorylation (all P < 0.05), which was abrogated by pretreatment with miR-21 overexpression. These findings indicate that miR-21-mediated inhibition of MC degranulation is involved in the anti-ACD effect of berberine via inhibiting p38 pathway, which provide a new insight into the immunopharmacological role of berberine and suggest its potential application for the treatment of allergic inflammation, such as ACD.
Chung, Kyung Min; Park, Hyunhee; Jung, Seonghee; Ha, Shinwon; Yoo, Seung-Jun; Woo, Hanwoong; Lee, Hyang Ju; Kim, Seong Who; Kim, Eun-Kyoung; Moon, Cheil; Yu, Seong-Woon
2015-10-01
Programmed cell death (PCD) has significant effects on the function of neural stem cells (NSCs) during brain development and degeneration. We have previously reported that adult rat hippocampal neural stem (HCN) cells underwent autophagic cell death (ACD) rather than apoptosis following insulin withdrawal despite their intact apoptotic capabilities. Here, we report a switch in the mode of cell death in HCN cells with calpain as a critical determinant. In HCN cells, calpain 1 expression was barely detectable while calpain 2 was predominant. Inhibition of calpain in insulin-deprived HCN cells further augmented ACD. In contrast, expression of calpain 1 switched ACD to apoptosis. The proteasome inhibitor lactacystin blocked calpain 2 degradation and elevated the intracellular Ca(2+) concentration. In combination, these effects potentiated calpain activity and converted the mode of cell death to apoptosis. Our results indicate that low calpain activity, due to absence of calpain 1 and degradation of calpain 2, results in a preference for ACD over apoptosis in insulin-deprived HCN cells. On the other hand, conditions leading to high calpain activity completely switch the mode of cell death to apoptosis. This is the first report on the PCD mode switching mechanism in NSCs. The dynamic change in calpain activity through the proteasome-mediated modulation of the calpain and intracellular Ca(2+) levels may be the critical contributor to the demise of NSCs. Our findings provide a novel insight into the complex mechanisms interconnecting autophagy and apoptosis and their roles in the regulation of NSC death. © 2015 AlphaMed Press.
Nickel Allergy and Our Children's Health: A Review of Indexed Cases and a View of Future Prevention.
Jacob, Sharon E; Goldenberg, Alina; Pelletier, Janice L; Fonacier, Luz S; Usatine, Richard; Silverberg, Nanette
2015-01-01
Nickel is the leading cause of allergic contact dermatitis (ACD) from early childhood through adolescence. Studies have shown that skin piercings and other nickel-laden exposures can trigger the onset of nickel ACD in those who are susceptible. Nickel ACD causes a vast amount of cutaneous disease in children. Cases of nickel ACD in children have been reported in peer-reviewed literature from 28 states. Common items that contain inciting nickel include jewelry, coins, zippers, belts, tools, toys, chair studs, cases for cell phones and tablets, and dental appliances. The diagnosis of nickel ACD has been routinely confirmed by patch testing in children older than 6 months suspected of ACD from nickel. Unlike in Europe, there are no mandatory restrictions legislated for nickel exposure in the United States. Denmark has demonstrated that regulation of the nickel content in metals can lower the risk of ACD and the associated health care-related costs that arise from excess nickel exposure. To further awareness, this article reviews the prominent role of nickel in pediatric skin disease in the United States. It discusses the need for a campaign by caretakers to reduce nickel-related morbidity. Lastly, it promotes the model of European legislation as a successful intervention in the prevention of nickel ACD. © 2015 Wiley Periodicals, Inc.
Oleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Choi, Jin Kyeong; Oh, Hyun-Mee; Lee, Soyoung
2013-05-15
Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common allergic and inflammatory skin diseases caused by a combination of eczema, scratching, pruritus, and cutaneous sensitization with allergens. This paper examines whether oleanolic acid acetate (OAA) modulates AD and ACD symptoms by using an existing AD model based on the repeated local exposure of mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene to the ears of BALB/c mice. In addition, the paper uses a 2,4-dinitrofluorobenzene-sensitized local lymph node assay (LLNA) for the ACD model. The oral administration of OAA over a four-week period attenuated AD symptoms in terms of decreasedmore » skin lesions, epidermal thickness, the infiltration of immune cells (CD4{sup +} cells, eosinophils, and mast cells), and serum IgE, IgG2a, and histamine levels. The gene expression of Th1, Th2, Th17, and Th22 cytokines was reduced by OAA in the lymph node and ear tissue, and the LLNA verified that OAA suppressed ACD. The oral administration of OAA over a three-day period attenuated ACD symptoms in terms of ear thickness, lymphocyte proliferation, and serum IgG2a levels. The gene expression of Th1, Th2, and Th17 cytokines was reduced by OAA in the thymus and ear tissue. Finally, to define the underlying mechanism, this paper uses a TNF-α/IFN-γ-activated human keratinocyte (HaCaT) model. OAA inhibited the expression of cytokines and chemokines through the downregulation of NF-κB and MAPKs in HaCaT cells. Taken together, the results indicate that OAA inhibited AD and ACD symptoms, suggesting that OAA may be effective in treating allergic skin disorders. - Highlights: • OAA reduced both acute and chronic AD symptoms. • OAA had a controlling effect on the immune reaction for ACD. • The effect of OAA on allergic skin disorders was comparable to the cyclosporine A. • OAA might be a candidate for the treatment of allergic skin disorders.« less
2006-07-05
Spaceward Bound Program in Atacama Desert; shown here is a realtime webcast from Yungay, Chile vis satellite involving NASA Scientists and seven NASA Explorer school teachers. On the Ames end we find the Girl Scouts Space cookines robotic team. The robot nicknamed Zoe is looking for life in extreme environments in preparation for what might be encounter on Mars. (back row l-r) Yvonne Clearwater, Ames Education Division, Donald James, Ames Education Division Chief, Pete Worden, Ames Center Director, Angela Diaz, Ames Director of Strategic Communications) see full text on the NASA-Ames News - Research # 04-91AR
Stoebner, Pierre E; Rahmoun, Massilva; Ferrand, Christophe; Meunier, Laurent; Yssel, Hans; Pène, Jérôme
2006-08-01
Solar ultraviolet (UV) radiation has hazardous effects on human health that are, in part, associated with its immunosuppressive effects via the induction of interleukin (IL)-10 production. Although IL-10 is produced by both T helper type 2 (Th2) cells and T-regulatory type 1 (Tr1) cells, the relative contribution of either subset in UV radiation-induced immunosuppression has not been established. Here, we show that T cells isolated from non-treated allergic contact dermatitis (ACD) reactions, 48 h following nickel challenge and propagated for 7-10 days in the presence of IL-2, were mainly CD4(+) and produced IL-10, but little interferon-gamma. A single sub-erythematous solar-simulated radiation (SSR) prior to antigen challenge exposure resulted in a clinical attenuation of the intensity of ACD reactions which was associated with a significant increase in both the magnitude of IL-10 production by skin-infiltrating T cells and the frequency of IL-10-producing Tr1 cells. Skin-infiltrating T cells in SSR-exposed, as well as non-exposed, ACD reactions showed a perturbed T-cell receptor (TCR)-Vbeta repertoire, without overexpression of a particular TCR-Vbeta gene product, indicating the presence of high frequencies of nickel non-specific T cells in ACD reactions. These results show that a single sub-erythematous SSR induces immunosuppression via the cutaneous infiltration of IL-10-producing Tr1, and to a lesser extent, Th2 cells.
Guerra, Marta G; Silva, Andreia M M; Marques, Sara H M; Melo, Sofia H; Póvoa, João A; Lobo, Conceição; Murta, Joaquim Neto
2017-01-01
To compare endothelial cell (EC) variation after anterior chamber phakic intraocular lens (AC-pIOL) implantation in highly myopic patients with a preoperative anterior chamber depth (ACD) between 2.8 and 3.0 versus ≥3.0 mm. A total of 280 eyes submitted to primary AC-pIOL implantation were analyzed. Pre- and postoperative values for uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, ACD (endothelial surface), and EC count were collected. The eyes were divided into 2 groups: group A - ACD between 2.8 and 3.0 mm; group B - ACD ≥3.0 mm. Mean global EC loss (ECL) and loss for each ACD group, according to pIOL type, were analyzed. Significant improvement of the spherical equivalent (-11.38 ± 4.57 vs. -0.49 ± 0.79; p = 0.000) and a significant decrease in EC density (2,810.95 ± 343.88 vs. 2,584.09 ± 374.88 cells/mm2; p = 0.000) were noted. The mean annual ECL was -2.19 ± 3.97%. Regarding group A (n = 80), a mean annual ECL of -2.06 ± 3.88% was registered, higher for the Acrysof Cachet® subtype, while group B (n = 200) showed -2.25 ± 4.01% ECL, higher for the Verisyse® subtype. There was no significant difference between the groups (p = 0.96). AC-pIOL implantation significantly improves the spherical equivalent in myopic patients. The mean annual ECL after pIOL implantation was higher in the larger ACD group, but this value was not statistically significant. A 2.8-mm ACD value seems to be a safe cutoff for AC-pIOL implantation. © 2017 S. Karger AG, Basel.
Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL.
Ito, Tomohisa; Ando, Takashi; Suzuki-Karasaki, Miki; Tokunaga, Tomohiko; Yoshida, Yukihiro; Ochiai, Toyoko; Tokuhashi, Yasuaki; Suzuki-Karasaki, Yoshihiro
2018-05-21
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cold plasma-stimulated medium (PSM) are promising novel anticancer tools due to their strong anticancer activities and high tumor-selectivity. The present study demonstrated that PSM and TRAIL may trigger autophagy in human malignant melanoma and osteosarcoma cells. Live-cell imaging revealed that even under nutritional and stress-free conditions, these cells possessed a substantial level of autophagosomes, which were localized in the cytoplasm separately from tubular mitochondria. In response to cytotoxic levels of PSM, the mitochondria became highly fragmented, and aggregated and colocalized with the autophagosomes. The cytotoxic effects of PSM were suppressed in response to various pharmacological autophagy inhibitors, including 3-methyladenine (3-MA) and bafilomycin A1, thus indicating the induction of autophagic cell death (ACD). Lethal levels of PSM also resulted in non-apoptotic, non-autophagic cell death in a reactive oxygen species-dependent manner under certain circumstances. Furthermore, TRAIL exhibited only a modest cytotoxicity toward these tumor cells, and did not induce ACD and mitochondrial aberration. The combined use of TRAIL and subtoxic concentrations of 3-MA resulted in decreased basal autophagy, increased mitochondrial aberration, colocalization with autophagosomes and apoptosis. These results indicated that PSM may induce ACD, whereas TRAIL may trigger cytoprotective autophagy that compromises apoptosis. To the best of our knowledge, the present study is the first to demonstrate that PSM can induce ACD in human cancer cells. These findings provide a rationale for the advantage of PSM over TRAIL in the destruction of apoptosis-resistant melanoma and osteosarcoma cells.
Evidence for ACD5 ceramide kinase activity involvement in Arabidopsis response to cold stress.
Dutilleul, Christelle; Chavarria, Heidy; Rézé, Nathalie; Sotta, Bruno; Baudouin, Emmanuel; Guillas, Isabelle
2015-12-01
Although sphingolipids emerged as important signals for plant response to low temperature, investigations have been limited so far to the function of long-chain base intermediates. The formation and function of ceramide phosphates (Cer-Ps) in chilled Arabidopsis were explored. Cer-Ps were analysed by thin layer chromatography (TLC) following in vivo metabolic radiolabelling. Ceramide kinase activity, gene expression and growth phenotype were determined in unstressed and cold-stressed wild type (WT) and Arabidopsis ceramide kinase mutant acd5. A rapid and transient formation of Cer-P occurs in cold-stressed WT Arabidopsis plantlets and cultured cells, which is strongly impaired in acd5 mutant. Although concomitant, Cer-P formation is independent of long-chain base phosphate (LCB-P) formation. No variation of ceramide kinase activity was measured in vitro in WT plantlets upon cold stress but the activity in acd5 mutant was further reduced by cold stress. At the seedling stage, acd5 response to cold was similar to that of WT. Nevertheless, acd5 seed germination was hypersensitive to cold and abscisic acid (ABA), and ABA-dependent gene expression was modified in acd5 seeds when germinated at low temperature. Our data involve for the first time Cer-P and ACD5 in low temperature response and further underline the complexity of sphingolipid signalling operating during cold stress. © 2015 John Wiley & Sons Ltd.
Acellular derivatives of mesenchymal stem cells prevent peritoneal adhesions in an animal model.
Rojo, Daniel; Conget, Paulette
2018-03-01
Peritoneal adhesions are nonanatomical connections that bind organs to the abdominal wall or among them. They arise after peritoneal injury, which triggers an inflammatory response followed by a healing process that leads to fibrotic tissue formation. Mesenchymal stem cells and their secretion products, also referred to as acellular derivatives (ACDs), have anti-inflammatory, fibrinolytic, and antifibrogenic properties. The aim of this study was to determine the effect of intraoperative administration of ACD on the appearance, severity, and progression of peritoneal adhesions, in an animal model. Cecal erosions were mechanically induced in adult mice. Before closure, the vehicle, ACD, or Seprafilm was administered. Seven days later, the presence and grade of peritoneal adhesions were assessed macroscopically. One, 3, and 7 d after intervention, molecular and cellular markers of inflammation, fibrinolysis, and fibrogenesis were evaluated both locally and systemically. ACDs avoided the appearance of clinically relevant peritoneal adhesions. The vehicle had no effect, and Seprafilm reduced them inconsistently. The antiadhesive effect of ACD was associated with an early reduction of proinflammatory cytokine (tumor necrosis factor-alpha and interferon-gamma) secretion and leukocyte (polymorphonuclears, mononuclears, and macrophages) infiltration. High levels of D-dimer, low fibrin deposits, low myofibroblasts infiltration, and less fibrosis were also observed. ACD administered at the end of abdominal surgeries prevents the formation of peritoneal adhesions due to the modulation of inflammatory, fibrinolytic, and fibrogenic processes. Copyright © 2017 Elsevier Inc. All rights reserved.
Wanner, G A; Mica, L; Wanner-Schmid, E; Kolb, S A; Hentze, H; Trentz, O; Ertel, W
1999-07-01
Using a murine model, we studied the effect of agonistic anti-CD95 antibodies (aCD95) on sinusoidal lining cells and a potential protection by caspase inhibition. C3H/HeN mice were intravenously administered aCD95 (10 microgram/mouse) or unspecific IgG (control) in the presence or absence of the caspase inhibitor z-VAD-fmk. Analysis of hepatic microcirculation using intravital fluorescence microscopy revealed severe (P<0.01) sinusoidal perfusion failure and reduced (P<0.05) phagocytic activity of Kupffer cells (KC) within 2 h. Transmission electron micrographs demonstrated loss of integrity of sinusoidal endothelial cells as early as 1 h after aCD95 application, whereas histological manifestation of hepatocellular apoptosis and hemorrhagic necrosis was most pronounced at 6 h. Blocking of caspase activity attenuated (P<0.01) both hepatic microvascular perfusion failure and KC dysfunction. Accordingly, full protection of the liver from apoptotic damage and intact microarchitecture was observed in histological sections after z-VAD-fmk treatment. Mortality rate was 40% 6 h after aCD95 administration, whereas all animals survived in the z-VAD-fmk group (P<0.05). The activation of caspases through CD95 may primarily lead to damage of sinusoidal endothelial cells and hepatic microvascular perfusion failure. Moreover, reduced phagocytic capacity of KC may contribute to accumulation of toxic metabolites released by dying cells at the local site of inflammation, further aggravating liver injury.
The RING-Type E3 Ligase XBAT35.2 Is Involved in Cell Death Induction and Pathogen Response1[OPEN
Liu, Hongxia; Ravichandran, Sridhar; McVey, Sarah; Lilley, Carly; Teresinski, Howard J.; Gonzalez-Ferrer, Carmen; Prithiviraj, Balakrishnan
2017-01-01
XBAT35 belongs to a subfamily of Arabidopsis (Arabidopsis thaliana) RING-type E3s that are similar in domain architecture to the rice (Oryza sativa) XA21 Binding Protein3, a defense protein. The XBAT35 transcript undergoes alternative splicing to produce two protein isoforms, XBAT35.1 and XBAT35.2. Here, we demonstrate that XBAT35.2 localizes predominantly to the Golgi and is involved in cell death induction and pathogen response. XBAT35.2, but not XBAT35.1, was found to trigger cell death when overexpressed in tobacco (Nicotiana benthamiana) leaves and does so in a manner that requires its RING domain. Loss of XBAT35 gene function disrupts the plant’s ability to defend against pathogen attack, whereas overexpression of XBAT35.2 enhances resistance to pathogens. XBAT35.2 was found to be unstable and promotes its own degradation, suggesting self-regulation. Inoculation with virulent and avirulent strains of the bacterial pathogen Pseudomonas syringae pv tomato DC3000 results in a drastic reduction in the levels of ubiquitinated XBAT35.2 and an increase in the abundance of the E3. This implies that pathogen infection prohibits XBAT35.2 self-regulation and stabilizes the E3. In agreement with a role in defending against pathogens, XBAT35.2 interacts with defense-related Accelerated Cell Death11 (ACD11) in planta and promotes the proteasome-dependent turnover of ACD11 in cell-free degradation assays. In accordance with regulation by a stabilized XBAT35.2, the levels of ubiquitinated ACD11 increased considerably, and the abundance of ACD11 was reduced following pathogen infection. In addition, treatment of transgenic seedlings with a proteasome inhibitor results in the accumulation of ACD11, confirming proteasome-dependent degradation. Collectively, these results highlight a novel role for XBAT35.2 in cell death induction and defense against pathogens. PMID:28951488
Wang, Yanyan; Xu, Han; Zheng, Xiaodong; Wei, Haiming; Sun, Rui; Tian, Zhigang
2007-10-01
Human umbilical cord blood (CB) has recently been used as a source of stem cells in transplantation. NK cells derived from CB are the key effector cells involved in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). It was reported that the activity of CB NK cells was lower than that of adult peripheral blood (PB) NK cells. In this study, we analyzed the expression of some NK cell receptors and cytotoxicity-related molecules in CB and PB NK cells. The expressions of activating NK receptors, CD16, NKG2D and NKp46, did not show significant difference between CB and PB NK cells. But the expression of inhibitory receptor NKG2A/CD94 was significantly higher on CB NK cells. As to the effector function molecules, granzyme B was expressed significantly lower in CB NK cells, but the expressions of intracellular perforin, IFN-gamma, TNF-alpha and cell surface FasL and TRAIL did not show difference between CB and PB NK cells. The results indicated that the high expression of NKG2A/CD94 and low expression of granzyme B may be related with the reduced activity of CB NK cells.
Wang, Kaiping; Wu, Jun; Cheng, Fang; Huang, Xiao; Zeng, Fang; Zhang, Yu
2017-01-01
Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia. Furthermore, ASP inhibited NF- κ B p65 activation via the I κ B kinases- (IKKs-) I κ B α pathway, thereby reducing the secretion of interleukin-6 (IL-6) and TNF- α , which is known to inhibit erythropoiesis. Our findings indicate that ASP is a potential treatment option for patients suffering from ACD.
Smith, K J; Skelton, H G; Nelson, A; Wagner, K F; Hackley, B E
1997-01-01
Delayed hypersensitivity reactions (DTH) are lost with progression of HIV disease. This loss of DTH commonly occurs before the onset of opportunistic infections and is an independent predictor of disease progression. We wanted to determine whether patients in late HIV disease with a history of allergic contact dermatitis (ACD) to poison ivy continue to react to poison ivy. Twelve HIV+ patients with a past history of ACD to poison ivy were tested with an extract prepared from poison ivy leaves. All but 1 patient had CD4+ T cell counts < 200/microliters, and 5 patients had had an opportunistic infection. All 12 patients showed positive reactions ranging from mild erythema and infiltration to marked erythema with bulla formation. ACD is considered a variant of DTH, and as DTH results in a T helper 1 cytokine pattern. However, the antigen-specific effector cells in ACD may be more diverse than in DTH. This diversity could explain the continued reaction to some contact allergens in late disease and may be important in the use of contact allergens for immunotherapy.
Wang, Ying; D'Urso, Giulia
2012-01-01
Degenerin/epithelial Na+ channels (DEG/ENaCs) are voltage-independent Na+ or Na+/Ca2+ channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na+ transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in Gi protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca2+ when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity. PMID:21994266
Wang, Ying; D'Urso, Giulia; Bianchi, Laura
2012-01-01
Degenerin/epithelial Na(+) channels (DEG/ENaCs) are voltage-independent Na(+) or Na(+)/Ca(2+) channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na(+) transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in G(i) protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca(2+) when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity.
Zárský, Viktor; Potocký, Martin
2010-04-01
The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a 'recycling domain' (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase-effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants.
Osterberg, T; Norinder, U
2001-01-01
A method of modelling and predicting biopharmaceutical properties using simple theoretically computed molecular descriptors and multivariate statistics has been investigated for several data sets related to solubility, IAM chromatography, permeability across Caco-2 cell monolayers, human intestinal perfusion, brain-blood partitioning, and P-glycoprotein ATPase activity. The molecular descriptors (e.g. molar refractivity, molar volume, index of refraction, surface tension and density) and logP were computed with ACD/ChemSketch and ACD/logP, respectively. Good statistical models were derived that permit simple computational prediction of biopharmaceutical properties. All final models derived had R(2) values ranging from 0.73 to 0.95 and Q(2) values ranging from 0.69 to 0.86. The RMSEP values for the external test sets ranged from 0.24 to 0.85 (log scale).
Zhai, Xiuhong; Gao, Yong-Guang; Mishra, Shrawan K; Simanshu, Dhirendra K; Boldyrev, Ivan A; Benson, Linda M; Bergen, H Robert; Malinina, Lucy; Mundy, John; Molotkovsky, Julian G; Patel, Dinshaw J; Brown, Rhoderick E
2017-02-10
Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants include Arabidopsis accelerated-cell-death 11 mutant ( acd11 ). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, "soluble" phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1P versus glycolipid. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Springer, Tzvia I; Goebel, Erich; Hariraju, Dinesh; Finley, Natosha L
2014-10-10
Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD's β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD's β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (Rh) and reduced thermal stability in the mutant complex. Taken together, our data provide new structural insights into the β-hairpin's role in stabilizing interactions between CyaA-ACD and N-CaM. Copyright © 2014 Elsevier Inc. All rights reserved.
Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.
Świadek, Magdalena; Proost, Sebastian; Sieh, Daniela; Yu, Jing; Todesco, Marco; Jorzig, Christian; Rodriguez Cubillos, Andrés Eduardo; Plötner, Björn; Nikoloski, Zoran; Chae, Eunyoung; Giavalisco, Patrick; Fischer, Axel; Schröder, Florian; Kim, Sang-Tae; Weigel, Detlef; Laitinen, Roosa A E
2017-01-01
Hybrid necrosis is a common type of hybrid incompatibility in plants. This phenomenon is caused by deleterious epistatic interactions, resulting in spontaneous activation of plant defenses associated with leaf necrosis, stunted growth and reduced fertility in hybrids. Specific combinations of alleles of ACCELERATED CELL DEATH 6 (ACD6) have been shown to be a common cause of hybrid necrosis in Arabidopsis thaliana. Increased ACD6 activity confers broad-spectrum resistance against biotrophic pathogens but reduces biomass production. We generated 996 crosses among individuals derived from a single collection area around Tübingen (Germany) and screened them for hybrid necrosis. Necrotic hybrids were further investigated by genetic linkage, amiRNA silencing, genomic complementation and metabolic profiling. Restriction site associated DNA (RAD)-sequencing was used to understand genetic diversity in the collection sites containing necrosis-inducing alleles. Novel combinations of ACD6 alleles found in neighbouring stands were found to activate the A. thaliana immune system. In contrast to what we observed in controlled conditions, necrotic hybrids did not show reduced fitness in the field. Metabolic profiling revealed changes associated with the activation of the immune system in ACD6-dependent hybrid necrosis. This study expands our current understanding of the active role of ACD6 in mediating trade-offs between defense responses and growth in A. thaliana. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
Choi, Dae Woon; Kwon, Da-Ae; Jung, Sung Keun; See, Hye-Jeong; Jung, Sun Young; Shon, Dong-Hwa; Shin, Hee Soon
2018-05-26
Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1β and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.
Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis.
Scholzen, T E; Steinhoff, M; Bonaccorsi, P; Klein, R; Amadesi, S; Geppetti, P; Lu, B; Gerard, N P; Olerud, J E; Luger, T A; Bunnett, N W; Grady, E F; Armstrong, C A; Ansel, J C
2001-01-15
Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.
Chen, Fengyang; Ye, Xiaodi; Yang, Yadong; Teng, Tianli; Li, Xiaoyu; Xu, Shifang; Ye, Yiping
2015-04-15
The leaves and bark of Metasequoia glyptostroboides are used as anti-microbic, analgesic and anti-inflammatory drug for dermatic diseases in Chinese folk medicine. However, the pharmacological effects and material basis responsible for the therapeutic use of this herb have not yet been well studied. The objectives of this study were to evaluate the anti-inflammatory effects of the proanthocyanidin fraction from the bark of M. glyptostroboides (MGEB) and to elucidate its immunological mechanisms. The anti-inflammatory activity of MGEB was evaluated using 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in mice. Its potential mechanisms were further investigated by determining its effects on Con A-induced T cell activation and Th1/Th17 responses in vitro. Both intraperitoneal injection and oral administration of MGEB significantly reduced the ear swelling in DNFB-induced ACD mice. MGEB inhibited Con A-induced proliferation and the expression levels of cell surface molecules CD69 and CD25 of T cells in vitro. MGEB also significantly decreased the production of Th1/Th17 specific cytokines (IL-2, IFN-γ and IL-17) and down-regulated their mRNA expression levels in activated T-cells. MGEB could ameliorate ACD, at least in part, through directly inhibiting T cells activation and Th1/Th17 responses. Copyright © 2015 Elsevier GmbH. All rights reserved.
Evidence for a stepwise program of extrathymic T cell development within the human tonsil
McClory, Susan; Hughes, Tiffany; Freud, Aharon G.; Briercheck, Edward L.; Martin, Chelsea; Trimboli, Anthony J.; Yu, Jianhua; Zhang, Xiaoli; Leone, Gustavo; Nuovo, Gerard; Caligiuri, Michael A.
2012-01-01
The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin– cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34+CD38brightLin– cells; (c) CD34+CD1a+CD11c– cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34–CD1a+CD3–CD11c– cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e) CD34–CD1a+CD3+CD11c– cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre–T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development. PMID:22378041
The immunology of the porcine skin and its value as a model for human skin.
Summerfield, Artur; Meurens, François; Ricklin, Meret E
2015-07-01
The porcine skin has striking similarities to the human skin in terms of general structure, thickness, hair follicle content, pigmentation, collagen and lipid composition. This has been the basis for numerous studies using the pig as a model for wound healing, transdermal delivery, dermal toxicology, radiation and UVB effects. Considering that the skin also represents an immune organ of utmost importance for health, immune cells present in the skin of the pig will be reviewed. The focus of this review is on dendritic cells, which play a central role in the skin immune system as they serve as sentinels in the skin, which offers a large surface area exposed to the environment. Based on a literature review and original data we propose a classification of porcine dendritic cell subsets in the skin corresponding to the subsets described in the human skin. The equivalent of the human CD141(+) DC subset is CD1a(-)CD4(-)CD172a(-)CADM1(high), that of the CD1c(+) subset is CD1a(+)CD4(-)CD172a(+)CADM1(+/low), and porcine plasmacytoid dendritic cells are CD1a(-)CD4(+)CD172a(+)CADM1(-). CD209 and CD14 could represent markers of inflammatory monocyte-derived cells, either dendritic cells or macrophages. Future studies for example using transriptomic analysis of sorted populations are required to confirm the identity of these cells. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Aeronautics and Space Report of the President: Fiscal Year 2009 Activities
NASA Technical Reports Server (NTRS)
2009-01-01
In fiscal year 2009 (FY 09), the Exploration Systems Mission Directorate's (ESMD) Advanced Capabilities Division (ACD) provided critical research and technology products that reduced operational and technical risks for the flight systems being developed by the Constellation Program.1 These products addressed high-priority technology requirements for lunar exploration; risk mitigation related to astronaut health and performance; basic research in life and physical sciences using the International Space Station (ISS), free-flying spacecraft, and ground-based laboratories; and lunar robotic missions to gather data relevant to future human lunar missions.
Ouyang, Liang; Zhang, Lan; Fu, Leilei; Liu, Bo
2017-04-03
ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) data set, tissue microarray-based analyses and multiple biologic evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC. Moreover, such new inspiring findings may help us discover that this activator of ULK1 (LYN-1604) with its anti-tumor activity and ACD-modulating mechanisms can be further exploited as a small-molecule candidate drug for future TNBC therapy.
Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.
György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I
2014-02-01
Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.
Pattmöller, Johanna; Wang, Jiong; Zemova, Elena; Seitz, Berthold; Eppig, Timo; Langenbucher, Achim; Szentmáry, Nóra
2015-09-01
To analyze corneal surface temperature profile in a young and healthy study population and to determine the impact of corneal thickness (CT), anterior chamber depth (ACD), and endothelial cell density (ECD) on surface temperature. In this prospective, single-center study 61 healthy right eyes of 61 subjects without tear film pathologies (mean age 24.9 ± 6.7 years) were recruited. Ocular surface temperature (OST) was measured with the Ocular Surface Thermographer TG-1000. From Pentacam HR CT and ACD, and from specular microscopy ECD and central corneal thickness (CCT) were acquired. From the raw measurement data (OST, CT and ACD) we extracted a) local OST the corneal center and 3mm away from the center at the 3, 6, and 9 o'clock positions, and b) Zernike parameters Z1, Z2 and Z3 to evaluate the general temperature profile within a 6mm circular area around the center. Overall, there was no correlation between OST and CT, ACD or ECD. Local OST did not correlate with CT at any measurement position. On average local OST was highest at measurement positions where CT was lowest, but without reaching statistical significance. Baseline OST was highest at thin corneal regions and temperature decay over time was smallest in those regions. Z1, Z2 and Z3 correlated well with CT. In healthy subjects corneal thickness, endothelial cell density and anterior chamber depth have no effect on corneal surface temperature. The general temperature profile seems to be influenced by the corneal thickness profile effecting a higher temperature and lower decay at thinner corneal regions. Copyright © 2014. Published by Elsevier GmbH.
Dalmarco, Eduardo Monguilhott; Medeiros, Yara Santos
2008-01-01
The mouse model of pleurisy induced by carrageenan is characterized by a significant enhancement of cell migration due to neutrophils 4 h after pleurisy induction. Forty-eight hours after pleurisy induction, a significant increase in cell migration due to mononuclear cells occurs. Recently, studies in our laboratory have demonstrated that cyclosporine A (CsA) inhibits leukocyte migration in the pleural cavity and lungs in the mouse model of pleurisy induced by carrageenan. In the present work we evaluated whether CsA was able to downregulate CD11a/CD18 adhesion molecule in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity in this model. Our results showed that CsA significantly decreased CD11a/CD18 in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity 4 h and 48 h after pleurisy induction. It is our hypothesis that the inhibitory effect elicited by CsA upon these adhesion molecules may be also be attributed to the downregulation of TNFα and IL-1β cytokines. PMID:19262158
Ohshima, Shiro; Ishii, Masaru; Asada, Hideo; Tatekawa, Toyoshi; Yamaguchi, Norihiko; Kobayashi, Hideyuki; Ishii, Taeko; Mima, Toru; Kawase, Ichiro; Saeki, Yukihiko
2002-08-01
We report the case of a young female patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). She showed a marked increase of NK cell population in peripheral blood. The NK cell population was suggested to be infected with EBV, and to be oligoclonal by Southern blotting using an EBV genome terminal-repeat probe. The NK cells aberrantly expressed CD25, a high affinity receptor for IL-2, and showed an augmented in vitro proliferative response to IL-2. Moreover, they also showed enhanced expression of both Fas-ligand and Bcl-2, and resistance to in vitro Fas-induced apoptotic cell death (Fas-ACD). Taken together, these observations suggested that both the augmentation of proliferative response to IL-2 and the decrease in Fas-ACD may cause NK cell lineage granular lymphocyte proliferative disorder (NK-GLPD) in patients with CAEBV and SHMB.
The role of skin barrier in occupational contact dermatitis.
Jakasa, Ivone; Thyssen, Jacob P; Kezic, Sanja
2018-06-12
Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis, which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier is different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signaling pathways during the sensitization phase required for the activation of T-cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens, but also by generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to development of ICD and ACD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
NASA Astrophysics Data System (ADS)
Zhan, Shuiqing; Wang, Junfeng; Wang, Zhentao; Yang, Jianhong
2018-02-01
The effects of different cell design and operating parameters on the gas-liquid two-phase flows and bubble distribution characteristics under the anode bottom regions in aluminum electrolysis cells were analyzed using a three-dimensional computational fluid dynamics-population balance model. These parameters include inter-anode channel width, anode-cathode distance (ACD), anode width and length, current density, and electrolyte depth. The simulations results show that the inter-anode channel width has no significant effect on the gas volume fraction, electrolyte velocity, and bubble size. With increasing ACD, the above values decrease and more uniform bubbles can be obtained. Different effects of the anode width and length can be concluded in different cell regions. With increasing current density, the gas volume fraction and electrolyte velocity increase, but the bubble size keeps nearly the same. Increasing electrolyte depth decreased the gas volume fraction and bubble size in particular areas and the electrolyte velocity increased.
Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.
Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D
2017-04-01
Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Landscape-Scale Controls on Aboveground Forest Carbon Stocks on the Osa Peninsula, Costa Rica
Taylor, Philip; Asner, Gregory; Dahlin, Kyla; Anderson, Christopher; Knapp, David; Martin, Roberta; Mascaro, Joseph; Chazdon, Robin; Cole, Rebecca; Wanek, Wolfgang; Hofhansl, Florian; Malavassi, Edgar; Vilchez-Alvarado, Braulio; Townsend, Alan
2015-01-01
Tropical forests store large amounts of carbon in tree biomass, although the environmental controls on forest carbon stocks remain poorly resolved. Emerging airborne remote sensing techniques offer a powerful approach to understand how aboveground carbon density (ACD) varies across tropical landscapes. In this study, we evaluate the accuracy of the Carnegie Airborne Observatory (CAO) Light Detection and Ranging (LiDAR) system to detect top-of-canopy tree height (TCH) and ACD across the Osa Peninsula, Costa Rica. LiDAR and field-estimated TCH and ACD were highly correlated across a wide range of forest ages and types. Top-of-canopy height (TCH) reached 67 m, and ACD surpassed 225 Mg C ha-1, indicating both that airborne CAO LiDAR-based estimates of ACD are accurate in tall, high-biomass forests and that the Osa Peninsula harbors some of the most carbon-rich forests in the Neotropics. We also examined the relative influence of lithologic, topoedaphic and climatic factors on regional patterns in ACD, which are known to influence ACD by regulating forest productivity and turnover. Analyses revealed a spatially nested set of factors controlling ACD patterns, with geologic variation explaining up to 16% of the mapped ACD variation at the regional scale, while local variation in topographic slope explained an additional 18%. Lithologic and topoedaphic factors also explained more ACD variation at 30-m than at 100-m spatial resolution, suggesting that environmental filtering depends on the spatial scale of terrain variation. Our result indicate that patterns in ACD are partially controlled by spatial variation in geologic history and geomorphic processes underpinning topographic diversity across landscapes. ACD also exhibited spatial autocorrelation, which may reflect biological processes that influence ACD, such as the assembly of species or phenotypes across the landscape, but additional research is needed to resolve how abiotic and biotic factors contribute to ACD variation across high biomass, high diversity tropical landscapes. PMID:26061884
March, Samanta M.; Culleré, Marcela E.; Abate, Paula; Hernández, José I.; Spear, Norman E.; Molina, Juan C.
2013-01-01
Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life. PMID:23785319
Bomberg, Hagen; Meiser, Franziska; Daume, Philipp; Bellgardt, Martin; Volk, Thomas; Sessler, Daniel I; Groesdonk, Heinrich V; Meiser, Andreas
2018-05-21
Volatile anesthetics are increasingly used for sedation in intensive care units. The most common administration system is AnaConDa-100 mL (ACD-100; Sedana Medical, Uppsala, Sweden), which reflects volatile anesthetics in open ventilation circuits. AnaConDa-50 mL (ACD-50) is a new device with half the volumetric dead space. Carbon dioxide (CO2) can be retained with both devices. We therefore compared the CO2 elimination and isoflurane reflection efficiency of both devices. A test lung constantly insufflated with CO2 was ventilated with a tidal volume of 500 mL at 10 breaths/min. End-tidal CO2 (EtCO2) partial pressure was measured using 3 different devices: a heat-and-moisture exchanger (HME, 35 mL), ACD-100, and ACD-50 under 4 different experimental conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS) conditions, BTPS with 0.4 Vol% isoflurane (ISO-0.4), and BTPS with 1.2 Vol% isoflurane. Fifty breaths were recorded at 3 time points (n = 150) for each device and each condition. To determine device dead space, we adjusted the tidal volume to maintain normocapnia (n = 3), for each device. Thereafter, we determined reflection efficiency by measuring isoflurane concentrations at infusion rates varying from 0.5 to 20 mL/h (n = 3), for each device. EtCO2 was consistently greater with ACD-100 than with ACD-50 and HME (ISO-0.4, mean ± standard deviations: ACD-100, 52.4 ± 0.8; ACD-50, 44.4 ± 0.8; HME, 40.1 ± 0.4 mm Hg; differences of means of EtCO2 [respective 95% confidence intervals]: ACD-100 - ACD-50, 8.0 [7.9-8.1] mm Hg, P < .001; ACD-100 - HME, 12.3 [12.2-12.4] mm Hg, P < .001; ACD-50 - HME, 4.3 [4.2-4.3] mm Hg, P < .001). It was greatest under ATP, less under BTPS, and least with ISO-0.4 and BTPS with 1.2 Vol% isoflurane. In addition to the 100 or 50 mL "volumetric dead space" of each AnaConDa, "reflective dead space" was 40 mL with ACD-100 and 25 mL with ACD-50 when using isoflurane. Isoflurane reflection was highest under ATP. Under BTPS with CO2 insufflation and isoflurane concentrations around 0.4 Vol%, reflection efficiency was 93% with ACD-100 and 80% with ACD-50. Isoflurane reflection remained sufficient with the ACD-50 at clinical anesthetic concentrations, while CO2 elimination was improved. The ACD-50 should be practical for tidal volumes as low as 200 mL, allowing lung-protective ventilation even in small patients.
red cells were assayed by ion exchange chromatography. The O-day 2,3- diphosphoglycerate concentrations of the ACD-AP bloods were below the normal...adenosine or guanosine. After a small initial increase, the ADP levels remained fairly constant. The AMP values increased as the ATP decreased and in
Thomas, C; Kobold, U; Balan, S; Roeddiger, R; Thomas, L
2011-04-01
Biochemical markers of iron deficiency do not distinguish iron-deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin-25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin-25 enables the differentiation of the states above in comparison with the ferritin index plot, the so-called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Serum hepcidin-25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin-25 was determined using an isotope-dilution micro-HPLC-tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin-25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Serum hepcidin-25 correlated with ferritin and the ferritin index. Use of a hepcidin-25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin-25 and the CHr). The hepcidin-25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin-25 alone. The combination of hepcidin-25 with CHr in the hepcidin-25 plot was useful for the differentiation of the states above. © 2010 Blackwell Publishing Ltd.
Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François
2015-04-20
During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Technical Reports Server (NTRS)
1976-01-01
The HEAO-B ACDS Review Team completed its four month assessment of the technical adequacy of the HEAO-B ACDS. As a result of its detailed analysis of the ACDS, the team found no reason why the ACDS will not perform its specified functions adequately. However, 23 concerns that point to potential difficulties were found and delineated; 18 of these are in the form of review item discrepancies.
DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma
Maes, Wim; Rosas, Georgina Galicia; Verbinnen, Bert; Boon, Louis; De Vleeschouwer, Steven; Ceuppens, Jan L.; Van Gool, Stefaan W.
2009-01-01
We studied the feasibility, efficacy, and mechanisms of dendritic cell (DC) immunotherapy against murine malignant glioma in the experimental GL261 intracranial (IC) tumor model. When administered prophylactically, mature DCs (DCm) ex vivo loaded with GL261 RNA (DCm-GL261-RNA) protected half of the vaccinated mice against IC glioma, whereas treatment with mock-loaded DCm or DCm loaded with irrelevant antigens did not result in tumor protection. In DCm-GL261-RNA–vaccinated mice, a tumor-specific cellular immune response was observed ex vivo in the spleen and tumor-draining lymph node cells. Specificity was also shown in vivo on the level of tumor challenge. Depletion of CD8+ T-cells by anti-CD8 treatment at the time of tumor challenge demonstrated their essential role in vaccine- mediated antitumor immunity. Depletion of CD25+ regulatory T-cells (Tregs) by anti-CD25 (aCD25) treatment strongly enhanced the efficacy of DC vaccination and was itself also protective, independently of DC vaccination. However, DC vaccination was essential to protect the animals from IC tumor rechallenge. No long-term protection was observed in animals that initially received aCD25 treatment only. In mice that received DC and/or aCD25 treatment, we retrieved tumor-specific brain-infiltrating cytotoxic T-lymphocytes. These data clearly demonstrate the effectiveness of DC vaccination for the induction of long-lasting immunological protection against IC glioma. They also show the beneficial effect of Treg depletion in this kind of glioma immunotherapy, even combined with DC vaccination. PMID:19336528
Galushko, E A
2014-01-01
The prevalence of anemia in patients with rheumatoid arthritis (RA) varies from 30 to 70%. 25% of the cases are diagnosed within 1 year after onset of the disease. On the whole, anemia in RA is described as anemia of a chronic disease (ACD). Pathogenesis ofACD is a multifactor process underlain by an immune mechanism: cytokines and cells ofthe reticuloendothelial system cause changes in iron homeostasis, proliferation of erythroid precursors, erythropoietin production and lifespan of erythrocytes. The key pathogenetic factor is disordered iron metabolism. IL-6 increasing hepatic production acute-phase protein (hepcidin) is the most important cytokine involved in ACD pathogenesis. Hence the necessity to measure its serum level for differential diagnostics of anemic syndrome in patients with RA and the choice of effective basal therapy. Recent data on the therapeutic potency of tocilizumab (IL-6 receptor inhibitor) demonstrate not its safety and sustainable beneficial clinical effect in combination with the favourable action on hemoglobin profile and reduction offatigue.
Biometric measurements in highly myopic eyes.
Shen, Peiyang; Zheng, Yingfeng; Ding, Xiaohu; Liu, Bin; Congdon, Nathan; Morgan, Ian; He, Mingguang
2013-02-01
To assess the repeatability and accuracy of optical biometry (Lenstar LS900 optical low-coherence reflectometry [OLCR] and IOLMaster partial coherence interferometry [PCI]) and applanation ultrasound biometry in highly myopic eyes. Division of Preventive Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, China. Comparative evaluation of diagnostic technology. Biometric measurements were taken in highly myopic subjects with a spherical equivalent (SE) of -6.00 diopters (D) or higher and an axial length (AL) longer than 25.0 mm. Measurements of AL and anterior chamber depth (ACD) obtained by OLCR were compared with those obtained by PCI and applanation A-scan ultrasound. Right eyes were analyzed. Repeatability was evaluated using the coefficient of variation (CoV) and agreement, using Bland-Altman analyses. The mean SE was -11.20 D ± 4.65 (SD). The CoVs for repeated AL measurements using OLCR, PCI, and applanation ultrasound were 0.06%, 0.07%, and 0.20%, respectively. The limits of agreement (LoA) for AL were 0.11 mm between OLCR and PCI, 1.01 mm between OLCR and applanation ultrasound, and 1.03 mm between PCI and ultrasound. The ACD values were 0.29 mm, 0.53 mm, and 0.51 mm, respectively. These repeatability and agreement results were comparable in eyes with extreme myopia (AL ≥ 27.0 mm) or posterior staphyloma. The mean radius of corneal curvature was similar between OLCR and PCI (7.66 ± 0.24 mm versus 7.64 ± 0.25 mm), with an LoA of 0.12 mm. Optical biometry provided more repeatable and precise measurements of biometric parameters, including AL and ACD, than applanation ultrasound biometry in highly myopic eyes. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Petrosino, Stefania; Verde, Roberta; Vaia, Massimo; Allarà, Marco; Iuvone, Teresa; Di Marzo, Vincenzo
2018-06-01
Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB 2 ) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD). We investigated if nonpsychotropic cannabinoids, such as cannabidiol (CBD), produced similar effects in this experimental model of ACD. HaCaT cells were stimulated with poly-(I:C), and the release of chemokines and cytokines was measured in the presence of CBD or other phytocannabinoids (such as cannabidiol acid, cannabidivarin, cannabidivarinic acid, cannabichromene, cannabigerol, cannabigerolic acid, cannabigevarin, tetrahydrocannabivarin, and tetrahydrocannabivarinic acid) and antagonists of CB 1 , CB 2 , or transient receptor potential vanilloid type-1 (TRPV1) receptors. HaCaT cell viability following phytocannabinoid treatment was also measured. The cellular levels of endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol] and related molecules (palmitoylethanolamide, oleoylethanolamide) were quantified in poly-(I:C)-stimulated HaCaT cells treated with CBD. We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor- α in a manner reversed by CB 2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5'-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect. This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.
2006-06-05
Space shuttle STS-121 FIT (Fly Immunity and Tumors) payload. Using Drosophila (fruit fly) to complete the experiments. Computer screen showing green fluorescent protein used to visualize blood cells in Drosophila (fruit fly).
Zanthoxylum fruit extract from Japanese pepper promotes autophagic cell death in cancer cells.
Nozaki, Reo; Kono, Toru; Bochimoto, Hiroki; Watanabe, Tsuyoshi; Oketani, Kaori; Sakamaki, Yuichi; Okubo, Naoto; Nakagawa, Koji; Takeda, Hiroshi
2016-10-25
Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) have multiple physiological activities (e.g., antiviral activity). However, the potential anticancer activity of ZFE has not been fully examined. In this study, we investigated the ability of ZFE to induce autophagic cell death (ACD). ZFE caused remarkable autophagy-like cytoplasmic vacuolization, inhibited cell proliferation, and ultimately induced cell death in the human cancer cell lines DLD-1, HepG2, and Caco-2, but not in A549, MCF-7, or WiDr cells. ZFE increased the level of LC3-II protein, a marker of autophagy. Knockdown of ATG5 using siRNA inhibited ZFE-induced cytoplasmic vacuolization and cell death. Moreover, in cancer cells that could be induced to undergo cell death by ZFE, the extract increased the phosphorylation of c-Jun N-terminal kinase (JNK), and the JNK inhibitor SP600125 attenuated both vacuolization and cell death. Based on morphology and expression of marker proteins, ZFE-induced cell death was neither apoptosis nor necrosis. Normal intestinal cells were not affected by ZFE. Taken together, our findings show that ZFE induces JNK-dependent ACD, which appears to be the main mechanism underlying its anticancer activity, suggesting a promising starting point for anticancer drug development.
Effect of (L)-cysteine on acetaldehyde self-administration.
Peana, Alessandra T; Muggironi, Giulia; Fois, Giulia R; Zinellu, Manuel; Sirca, Donatella; Diana, Marco
2012-08-01
Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered. This study examined the effects of l-cysteine pre-treatment during the acquisition and maintenance phases of ACD (0.2%) self-administration as well as on the deprivation effect after ACD extinction and on a progressive ratio (PR) schedule of reinforcement. In a separate PR schedule of reinforcement, the effect of l-cysteine was assessed on the break-point produced by ethanol (10%). Furthermore, we tested the effect of l-cysteine on saccharin (0.2%) reinforcement. Wistar rats were trained to self-administer ACD by nose poking on a fixed ratio (FR1) schedule in 30-min daily sessions. Responses on an active nose-poke caused delivery of ACD solution, whereas responses on an inactive nose-poke had no consequences. l-cysteine reduced the acquisition (40 mg/kg), the maintenance and the deprivation effect (100 mg/kg) of ACD self-administration. Furthermore, at the same dose, l-cysteine (120 mg/kg) decreased both ACD and ethanol break point. In addition, l-cysteine was unable to suppress the different responses for saccharin, suggesting that its effect did not relate to an unspecific decrease in a general motivational state. Compared to saline, l-cysteine did not modify responses on inactive nose-pokes, suggesting an absence of a non-specific behavioural activation. Taken together, these results could support the hypotheses that ACD possesses reinforcing properties and l-cysteine reduces motivation to self-administer ACD. Copyright © 2012 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Springer, Tzvia I.; Goebel, Erich; Hariraju, Dinesh
Highlights: • Bordetella pertussis adenylate cyclase toxin modulates bi-lobal structure of CaM. • The structure and stability of the complex rely on intermolecular associations. • A novel mode of CaM-dependent activation of the adenylate cyclase toxin is proposed. - Abstract: Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved throughmore » its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD’s β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD’s β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (R{sub h}) and reduced thermal stability in the mutant complex. Taken together, our data provide new structural insights into the β-hairpin’s role in stabilizing interactions between CyaA-ACD and N-CaM.« less
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-26
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... counsel to the ACD, CDC, regarding a broad range of public health ethics questions and issues arising from... strategy for addressing its charge to provide a preliminary overview to the ACD on ethical issues related...
Guevara, M A; Bauer, L L; Garleb, K A; Fahey, G C; de Godoy, M R C
2015-05-01
The objectives were to quantify gastrointestinal tolerance, total tract nutrient digestibility, and serum lipid profiles of dogs as affected by α-cyclodextrin (ACD) supplementation and to validate the accuracy of fat analyses techniques using novel ACD-fat complexes. The ACD was hydrolyzed and free sugars and hydrolyzed monosaccharides were quantified using high performance liquid chromatography. Known amount of fats were complexed with ACD, and fat content of complexes were determined using the ether extraction and acid-hydrolyzed fat methods. Nine mixed-breed hounds were used in a crossover design with 3 periods of 10 d each, including 6 d for diet adaptation and 4 d for fecal collection. Dogs were fed twice daily a diet with poultry byproduct meal and brewer's rice as the main ingredients, and chromic oxide (0.2%) was included as a digestion marker. Dogs were supplemented with either 0, 3, or 6 g of ACD diluted in 15 mL of water twice per day for a total of 0, 6, and 12 g ACD per day. The ACD had a very low free sugar concentration and, once hydrolyzed, released only glucose, as expected. Average daily food intake, fecal output (DM basis), and fecal scores were not significantly different among treatments. Body weight and condition score and serum triglycerides and cholesterol concentrations remained unaltered throughout the duration of the experiment. Dry matter, OM, and fat digestibility coefficients were lower (P < 0.05) for both treatment groups compared to the control. The acid-hydrolyzed fat method was valid to measure fat that was bound to ACD. Intake of ACD lowered fat digestibility somewhat but not to the extent previously reported, without affecting serum lipid concentrations or outcomes related to tolerance. Therefore, ACD supplementation resulted in a small decrease in fat digestibility, but ACD supplementation might have potential in modifying serum lipid profiles.
Plaisance, P; Lurie, K G; Payen, D
2000-03-07
Blood pressure is severely reduced in patients in cardiac arrest receiving standard cardiopulmonary resuscitation (CPR). Although active compression-decompression (ACD) CPR improves acute hemodynamic parameters, arterial pressures remain suboptimal with this technique. We performed ACD CPR in patients with a new inspiratory threshold valve (ITV) to determine whether lowering intrathoracic pressures during the "relaxation" phase of ACD CPR would enhance venous blood return and overall CPR efficiency. This prospective, randomized, blinded trial was performed in prehospital mobile intensive care units in Paris, France. Patients in nontraumatic cardiac arrest received ACD CPR plus the ITV or ACD CPR alone for 30 minutes during advanced cardiac life support. End tidal CO(2) (ETCO(2)), diastolic blood pressure (DAP) and coronary perfusion pressure, and time to return of spontaneous circulation (ROSC) were measured. Groups were similar with respect to age, gender, and initial rhythm. Mean maximal ETCO(2), coronary perfusion pressure, and DAP values, respectively (in mm Hg), were 13.1+/-0.9, 25.0+/-1.4, and 36.5+/-1.5 with ACD CPR alone versus 19.1+/-1.0, 43.3+/-1.6, and 56.4+/-1.7 with ACD plus valve (P<0.001 between groups). ROSC was observed in 2 of 10 patients with ACD CPR alone after 26.5+/-0.7 minutes versus 4 of 11 patients with ACD CPR plus ITV after 19.8+/-2.8 minutes (P<0.05 for time from intubation to ROSC). Conclusions-Use of an inspiratory resistance valve in patients in cardiac arrest receiving ACD CPR increases the efficiency of CPR, leading to diastolic arterial pressures of >50 mm Hg. The long-term benefits of this new CPR technology are under investigation.
Heydarian, Zohreh; Yu, Min; Gruber, Margaret; Glick, Bernard R.; Zhou, Rong; Hegedus, Dwayne D.
2016-01-01
Camelina sativa (camelina) is an oilseed crop touted for use on marginal lands; however, it is no more tolerant of soil salinity than traditional crops, such as canola. Plant growth-promoting bacteria (PGPB) that produce 1-aminocyclopropane-1-carboxylate deaminase (ACC deaminase) facilitate plant growth in the presence of abiotic stresses by reducing stress ethylene. Rhizospheric and endophytic PGPB and the corresponding acdS- mutants of the latter were examined for their ability to enhance tolerance to salt in camelina. Stimulation of growth and tolerance to salt was correlated with ACC deaminase production. Inoculation of soil with wild-type PGPB led to increased shoot length in the absence of salt, and increased seed production by approximately 30–50% under moderately saline conditions. The effect of ACC deaminase was further examined in transgenic camelina expressing a bacterial gene encoding ACC deaminase (acdS) under the regulation of the CaMV 35S promoter or the root-specific rolD promoter. Lines expressing acdS, in particular those using the rolD promoter, showed less decline in root length and weight, increased seed production, better seed quality and higher levels of seed oil production under salt stress. This study clearly demonstrates the potential benefit of using either PGPB that produce ACC deaminase or transgenic plants expressing the acdS gene under the control of a root-specific promoter to facilitate plant growth, seed production and seed quality on land that is not normally suitable for the majority of crops due to high salt content. PMID:28018305
Hsu, Wei-Cherng; Shen, Elizabeth P; Hsieh, Yi-Ting
2014-01-01
Aim of Study: To analyze the association between anterior chamber depth (ACD) and age, sex, and body height (BH). Materials and Methods: One thousand four hundred eighty eyes of 1480 adults 40 years of age and older receiving preoperative evaluation for cataract surgery were recruited consecutively from June 1, 2006, to December 31, 2010. ACD was measured with the Zeiss IOLMaster. Univariate and multivariate linear regression models were used to analyze the correlations, and receiving operator characteristic (ROC) curves and the area under the curve (AUC) were used for evaluating the predictability of an ACD less than 2.70 mm. Results: ACD was negatively correlated with age and positively correlated with BH in both univariate and multivariate regression analysis (P < 0.001). Sex was associated with ACD in univariate analysis, but not after adjustment with age and BH. In predicting an ACD less than 2.70 mm, the AUCs of ROC curves for ‘age and sex’, ‘age and BH’, and ‘age, sex, and BH’ were 0.687, 0.689, and 0.689, respectively. Conclusion: Age and BH were independent associating factors of ACD; however, sex was not. Older people and shorter ones likely had shallower ACD, and therefore were predisposed to Primary angle closure glaucoma (PACG). The predictability of ACD by age and BH solely was low, and adding sex did not increase it. PMID:24145564
Conctact dermatitis: some important topics.
Pigatto, P D
2015-11-01
Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred patients with suspected ACD ranges from 27 to 95.6%. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up.
SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, I; Lye, J; Alves, A
Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the threemore » professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a joint initiative between the Australian Department of Health and the Australian Radiation Protection and Nuclear Safety Agency.« less
Wang, Zhigang; Yi, Tao; Long, Man; Ding, Fengmin; Ouyang, Lichen; Chen, Zebin
2018-06-01
In this study, we aimed to investigate the effect of electro-acupuncture (EA) at the Zusanli acupoint (ST36) on interleukin (IL)-33-mediated mast cell activation. Firstly, 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in rats was developed with or without EA treatment. Then, rat peritoneal mast cells (RPMCs) were obtained and cultured in the presence of IL-33. EA treatment relieved ear swelling and reduced mast cell infiltration in the local inflammation area with DNFB challenge, accompanying the decrement of IL-33 production. RPMCs isolated from ACD rats with EA treatment showed significant downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation. However, there was no obvious difference in surface ST2 receptor expression among different groups. In addition, EA selectively altered IL-33 signaling, suppressing p38 phosphorylation as well as NF-κB- and AP-1-mediated transcription but not Akt phosphorylation. Importantly, EA lowered microRNA (miR)-155 expression in the RPMCs, which presented a positive correlation with IL-33-induced IL-6 production. Furthermore, overexpression of miR-155 in the RPMCs was established following miR-155 mimic transfection. RPMCs with the overexpressed miR-155 displayed an obvious increment of inflammatory cytokine and abrogated the inhibitive effect of EA on NF-κB- and AP-1-regulated transcription in response to IL-33 compared with those without transfected-miR-155. These findings demonstrate EA treatment inhibits NF-κB and AP-1 activation as well as promotes the negative feedback regulation of IL-33 signaling via targeting miR-155 in mast cells, which contribute to the anti-inflammatory effect of EA on DNFB-induced ACD in rats.
Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark
2013-09-23
Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. Published by Elsevier Ltd.
Aboveground Biomass Variability Across Intact and Degraded Forests in the Brazilian Amazon
NASA Technical Reports Server (NTRS)
Longo, Marcos; Keller, Michael; Dos-Santos, Maiza N.; Leitold, Veronika; Pinage, Ekena R.; Baccini, Alessandro; Saatchi, Sassan; Nogueira, Euler M.; Batistella, Mateus; Morton, Douglas C.
2016-01-01
Deforestation rates have declined in the Brazilian Amazon since 2005, yet degradation from logging, re, and fragmentation has continued in frontier forests. In this study we quantified the aboveground carbon density (ACD) in intact and degraded forests using the largest data set of integrated forest inventory plots (n 359) and airborne lidar data (18,000 ha) assembled to date for the Brazilian Amazon. We developed statistical models relating inventory ACD estimates to lidar metrics that explained70 of the variance across forest types. Airborne lidar-ACD estimates for intact forests ranged between 5.0 +/- 2.5 and 31.9 +/- 10.8 kg C m(exp -2). Degradation carbon losses were large and persistent. Sites that burned multiple times within a decade lost up to 15.0 +/- 0.7 kg C m(-2)(94%) of ACD. Forests that burned nearly15 years ago had between 4.1 +/- 0.5 and 6.8 +/- 0.3 kg C m(exp -2) (22-40%) less ACD than intact forests. Even for low-impact logging disturbances, ACD was between 0.7 +/- 0.3 and 4.4 +/- 0.4 kg C m(exp -2)(4-21%) lower than unlogged forests. Comparing biomass estimates from airborne lidar to existing biomass maps, we found that regional and pan-tropical products consistently overestimated ACD in degraded forests, under-estimated ACD in intact forests, and showed little sensitivity to res and logging. Fine-scale heterogeneity in ACD across intact and degraded forests highlights the benefits of airborne lidar for carbon mapping. Differences between airborne lidar and regional biomass maps underscore the need to improve and update biomass estimates for dynamic land use frontiers, to better characterize deforestation and degradation carbon emissions for regional carbon budgets and Reduce Emissions from Deforestation and forest Degradation(REDD+).
Anti-Coincidence Detector for GLAST
NASA Technical Reports Server (NTRS)
Moiseev, Alexander A.; Hartman, R. C.; Johnson, Thomas E.; Ormes, Jonathan F.; Thompson, D. J.
2004-01-01
The Anti-Coincidence Detector (ACD) is the outermost detector layer in the GLAST Large Area Telescope (LAT), surrounding the top and sides of the tracker. The purpose of the ACD is to detect and veto incident cosmic ray charged particles, which outnumber cosmic gamma rays by 3-5 orders of magnitude. The challenge in ACD design is that it has to have high (0.9997) detection efficiency for relativistic charged particles, but must have low sensitivity to backsplash photons. These are products of high energy interactions in the LAT calorimeter, and can cause a veto signal in the ACD resulting in degradation of the LAT efficiency for high energy (>10 GeV) gamma-rays. The ACD requirement is that backsplash shall not reduce the LAT sensitivity by more than 20% for gamma rays of 300 GeV. To solve this problem, the ACD is divided into 89 scintillating tiles, with wave-length shifting fiber readout. The detector design and its characteristics are given in this paper.
Mobile Phone Dermatitis in Children and Adults: A Review of the Literature
Richardson, Clare; Hamann, Dathan; Thyssen, Jacob P.
2014-01-01
Background: Mobile phones have been reported to cause allergic contact dermatitis (ACD). Methods: A comprehensive online literature review was conducted through the National Library of Medicine (Pubmed MEDLINE) using appropriate medical subject headings and keywords. Results: Thirty-seven cases of mobile phone-related ACD were found. Six studies evaluating allergen release from mobile phones were found. Conclusions: Case reports of mobile phone-associated ACD have risen rapidly in number since 2000. Case reports highlight mobile phone ACD in both pediatric and adult populations in many countries. Metal allergens, notably nickel and chromium, were frequently implicated in mobile phone associated ACD. Nickel release from mobile phones appears to be common and has been reported in both cheap and expensive mobile phones, including phones covered under the EU Nickel Directive. PMID:24963454
Gittler, Julia K.; Krueger, James G.; Guttman-Yassky, Emma
2014-01-01
Atopic dermatitis (AD), as well as irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), are common skin diseases. These diseases are characterized by skin inflammation mediated by activated innate immunity or acquired immune mechanisms. Although AD, ICD, and ACD can be encountered in pure forms by allergists and dermatologists, patients with AD often present with increased frequency of ICD and ACD. Although a disturbed barrier alone could potentiate immune reactivity in patients with AD through increased antigen penetration, additional immune mechanisms might explain the increased susceptibility of atopic patients to ICD and ACD. This review discusses cellular pathways associated with increased skin inflammation in all 3 conditions and presents mechanisms that might contribute to the increased rate of ICD and ACD in patients with AD. PMID:22939651
de Groot, Anton C; Maibach, Howard I
2010-03-01
Recent US studies have presented case series of patient with allergic contact dermatitis (ACD) allegedly caused by formaldehyde in clothes treated with durable-press chemical finishes (DPCF), which are known formaldehyde releasers. However, the amounts of formaldehyde released by modern DPCF are thought to be well below the levels previously estimated to be able to elicit ACD. The objectives of this review are (i) to investigate whether clothes sold in the USA may contain enough free formaldehyde to elicit ACD in previously sensitized individuals and (ii) to assess the validity of US reports on ACD from formaldehyde in DPCF treated clothes. Literature was examined using various resources. The threshold level for formaldehyde in clothes that may cause ACD in sensitized individuals is unknown; we present data suggesting that levels < 200 ppm will be safe for most patients and that textiles will rarely contain higher amounts. All US studies presenting patients with ACD from formaldehyde in clothes had some weaknesses and in no report was the diagnosis proven beyond doubt. Currently, there is no definite proof that textile ACD from formaldehyde in DPCF in the USA exists. Future research should be directed at establishing the elicitation threshold and the amounts of formaldehyde present in textiles.
Iskander, Deena; Psaila, Bethan; Gerrard, Gareth; Chaidos, Aristeidis; En Foong, Hui; Harrington, Yvonne; Karnik, Leena C; Roberts, Irene; de la Fuente, Josu; Karadimitris, Anastasios
2015-04-16
Diamond-Blackfan anemia (DBA) is a disorder characterized by a selective defect in erythropoiesis. Delineation of the precise defect is hampered by a lack of markers that define cells giving rise to erythroid burst- and erythroid colony-forming unit (BFU-E and CFU-E) colonies, the clonogenic assays that quantify early and late erythroid progenitor (EEP and LEP) potential, respectively. By combining flow cytometry, cell-sorting, and single-cell clonogenic assays, we identified Lin(-)CD34(+)CD38(+)CD45RA(-)CD123(-)CD71(+)CD41a(-)CD105(-)CD36(-) bone marrow cells as EEP giving rise to BFU-E, and Lin(-)CD34(+/-)CD38(+)CD45RA(-)CD123(-)CD71(+)CD41a(-)CD105(+)CD36(+) cells as LEP giving rise to CFU-E, in a hierarchical fashion. We then applied these definitions to DBA and identified that, compared with controls, frequency, and clonogenicity of DBA, EEP and LEP are significantly decreased in transfusion-dependent but restored in corticosteroid-responsive patients. Thus, both quantitative and qualitative defects in erythroid progenitor (EP) contribute to defective erythropoiesis in DBA. Prospective isolation of defined EPs will facilitate more incisive study of normal and aberrant erythropoiesis. © 2015 by The American Society of Hematology.
Anterior chamber depth studies.
Hoffer, Kenneth J; Savini, Giacomo
2015-09-01
To compare the anterior chamber depth (ACD; corneal epithelium to lens) using 3 modalities and compare the change 1 day and 3 months postoperatively. Private practice, Santa Monica, California, USA. Nonrandomized prospective series. The mean optical pachymetry and immersion ultrasound (US) of the ACD and partial coherence interferometry (PCI) were measured. Optical pachymetry ACD was measured in 675 eyes postoperatively at 1 day and 3 months. The optical pachymetry ACD in 492 eyes was 3.17 mm ± 0.42 (SD); by immersion US, it was 2.99 ± 0.51 mm (0.18 mm deeper; P < .0001). In 178 eyes, the optical pachymetry ACD was 3.23 ± 0.45 mm; the PCI was 3.19 ± 0.48 mm (0.04 mm deeper), which was not statistically different (P > .05). In 675 eyes, optical pachymetry ACD preoperatively was 3.19 ± 0.40 mm. The postoperative 1-day optical pachymetry ACD was 4.35 ± 0.35 mm with a mean refractive error of -0.30 diopter (D); the final 3-month optical pachymetry ACD was 4.47 ± 0.31 mm, with a mean refractive error of -0.07 D (P < .0001). This is a mean intraocular lens (IOL) position shift of +0.12 mm posteriorly; the +0.23 D change represents a ratio of 1.92 D/mm of IOL axial movement. The PCI ACD was comparable with optical pachymetry, but careful immersion US led to a 0.18 mm shorter ACD reading that cannot be corrected by sound velocity. The posterior capsule contracted and moved the IOL posteriorly 0.12 mm, resulting in 0.23 D hyperopic shift. Dr. Hoffer owns the registered trademark name "Hoffer(®)" and receives royalties for its commercial use from Alcon Laboratories, Inc., Appasamy Associates, Carl Zeiss Meditec AG, DGH Technology, Inc., Ellex iScience, Inc., Haag-Streit AG, Nidek Co., Ltd., Tomey Corp., Topcon Medical Systems, Inc., and Ziemer USA, Inc., as well as royalties from Slack, Inc. for the textbook IOL Power. Neither author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Guintran, Jean-Olivier; Iata, Harry; Anderson, Karen; Nausien, Johnny; Gresty, Karryn J; Waters, Norman C.; Vestergaard, Lasse S.; Taleo, George; Cheng, Qin
2016-01-01
Background As part of efforts to eliminate malaria, Vanuatu has piloted the implementation of enhanced malaria surveillance and response strategies since 2011. This involves passive case detection (PCD) in health facilities, proactive case detection (Pro-ACD) and reactive case detection (Re-ACD) in communities using malaria rapid diagnostic tests (RDTs). While RDTs improve case management, their utility for detection of malaria infections in ACDs in this setting is unclear. Methods The utility of malaria RDTs as diagnostic tools was evaluated in PCD, in five rounds of Pro-ACDs and five rounds of Re-ACDs conducted in Tafea and Torba Provinces between 2011 and 2014. The number of malaria infections detected by RDTs was compared to that detected by PCR from collected used-RDTs. Results PCD in Tafea Province (2013) showed a RDT-positive rate of 0.21% (2/939) and a PCR-positive rate of 0.44% (2/453), indicating less than 1% of suspected malaria cases in Tafea Province were due to malaria. In Pro-ACDs conducted in Tafea and Torba Provinces, RDT-positive rates in 2013 and 2014 were 0.14% (3/2145) and 0% (0/2823), respectively, while the corresponding PCR-positive rates were 0.72% (9/1242) and 0.79% (9/1141). PCR identified villages in both provinces appearing to be transmission foci with a small number of low-density infections, mainly P. falciparum infections. In five rounds of Re-ACD, RDTs did not identify any additional infections while PCR detected only one among 173 subjects screened. Conclusions PCD and Pro-ACDs demonstrate that both Tafea and Torba Provinces in Vanuatu has achieved very low malaria prevalence. In these low-transmission areas, conducting Pro-ACD and Re-ACDs using RDTs appears not cost-effective and may have limited impact on interrupting malaria transmission due to the small number of infections identified by RDTs and considerable operational resources invested. More sensitive, field deployable and affordable diagnostic tools will improve malaria surveillance in malaria elimination settings. PMID:27902755
Debaty, Guillaume; Lurie, Keith; Metzger, Anja; Lick, Michael; Bartos, Jason A; Rees, Jennifer N; McKnite, Scott; Puertas, Laura; Pepe, Paul; Fowler, Raymond; Yannopoulos, Demetris
2016-08-01
Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. Prospective animal investigation. Animal laboratory Female farm pigs (n=46, 39±1kg). Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p=0.05). There were no significant differences in 24h survival between groups. LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p=0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone (p=0.027). BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. 12-11. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
This report provides a detailed summary of the activities carried out to sample groundwater at Waste Area Grouping (WAG) 6. The analytical results for samples collected during Phase 1, Activity 2 of the WAG 6 Resource Conservation and Recovery Act Facility Investigation (RFI) are also presented. In addition, analytical results for Phase 1, activity sampling events for which data were not previously reported are included in this TM. A summary of the groundwater sampling activities of WAG 6, to date, are given in the Introduction. The Methodology section describes the sampling procedures and analytical parameters. Six attachments are included. Attachmentsmore » 1 and 2 provide analytical results for selected RFI groundwater samples and ORNL sampling event. Attachment 3 provides a summary of the contaminants detected in each well sampled for all sampling events conducted at WAG 6. Bechtel National Inc. (BNI)/IT Corporation Contract Laboratory (IT) RFI analytical methods and detection limits are given in Attachment 4. Attachment 5 provides the Oak Ridge National Laboratory (ORNL)/Analytical Chemistry Division (ACD) analytical methods and detection limits and Resource Conservation and Recovery Act (RCRA) quarterly compliance monitoring (1988--1989). Attachment 6 provides ORNL/ACD groundwater analytical methods and detection limits (for the 1990 RCRA semi-annual compliance monitoring).« less
Controls over aboveground forest carbon density on Barro Colorado Island, Panama
NASA Astrophysics Data System (ADS)
Mascaro, J.; Asner, G. P.; Muller-Landau, H. C.; van Breugel, M.; Hall, J.; Dahlin, K.
2011-06-01
Despite the importance of tropical forests to the global carbon cycle, ecological controls over landscape-level variation in live aboveground carbon density (ACD) in tropical forests are poorly understood. Here, we conducted a spatially comprehensive analysis of ACD variation for a continental tropical forest - Barro Colorado Island, Panama (BCI) - and tested site factors that may control such variation. We mapped ACD over 1256 ha of BCI using airborne Light Detection and Ranging (LiDAR), which was well-correlated with ground-based measurements of ACD in Panamanian forests of various ages (r2 = 0.84, RMSE = 17 Mg C ha-1, P < 0.0001). We used multiple regression to examine controls over LiDAR-derived ACD, including slope angle, forest age, bedrock, and soil texture. Collectively, these variables explained 14 % of the variation in ACD at 30-m resolution, and explained 33 % at 100-m resolution. At all resolutions, slope (linked to underlying bedrock variation) was the strongest driving factor; standing carbon stocks were generally higher on steeper slopes. This result suggests that physiography may be more important in controlling ACD variation in Neotropical forests than currently thought. Although BCI has been largely undisturbed by humans for a century, past land-use over approximately half of the island still influences ACD variation, with younger forests (80-130 years old) averaging ~15 % less carbon storage than old-growth forests (>400 years old). If other regions of relatively old tropical secondary forests also store less carbon aboveground than primary forests, the effects on the global carbon cycle could be substantial and difficult to detect with traditional satellite monitoring.
Guevara, M A; Bauer, L L; Garleb, K A; Fahey, G C; de Godoy, M R C
2016-05-01
The objectives were to examine in vitro fermentation characteristics, in vivo nutrient digestibility, fecal microbiota, and serum lipid profiles as affected by α-cyclodextrin (ACD) supplementation. Short-chain fatty acid (SCFA) production was measured after in vitro fermentation for 3, 6, 9, and 12 h of ACD, β-cyclodextrin, and γ-cyclodextrin. Five mixed-breed hounds were used in a Latin square design. Each experimental period comprised 14 d, including 10 d for diet adaptation and 4 d for fecal collection. Dogs were fed, twice a day, an extruded diet made with poultry byproduct meal and brewer's rice as the main ingredients. Dogs were supplemented with 0, 1, 2, 3, or 4 g of ACD diluted in 15 mL of water twice daily for a total of 0, 2, 4, 6, and 8 g ACD/d. Maximal in vitro production of total SCFA was lowest for ACD. However, the greatest maximal production of propionate was noted for ACD treatment. Total tract nutrient digestibility and fecal DM concentration linearly decreased ( < 0.05) for treatment groups receiving ACD; no changes were observed for ileal digestibility. Serum cholesterol and triglyceride concentrations were within normal ranges for dogs and were not different among treatments. Similarly, no changes in fecal microbiota were observed. Overall, ACD supplementation appears to have no effect on nutrient absorption in the small intestine but may alter fermentation in the large bowel, which could lead to a higher proportion of propionate production as observed in the in vitro experiment.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-08
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... ACD, CDC, regarding a broad range of public health ethics questions and issues arising from programs... ethics standards to the accreditation process for public health departments; ethical considerations...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-18
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... will provide counsel to the ACD, CDC, regarding a broad range of public health ethics questions and... territorial health departments in their efforts to address public health ethics challenges, approaches for...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-23
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... of public health ethics questions and issues arising from programs, scientists and practitioners... April 28, 2011, ACD, CDC meeting; discussion of next steps on addressing potential public health ethical...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-02-22
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC): Notice of Charter Renewal.... Contact Person for More Information: Anne C. Haddix, PhD, Designated Federal Officer, ACD, CDC, 1600...
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2010-10-05
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Health Disparities... provide recommendations for consideration to the ACD on strategic and other broad issues facing CDC... collaboration with the CDC Health Equity Workgroup; CDC Director's Annual Health Disparity Report; and briefing...
Movie Lessons for New Learning
ERIC Educational Resources Information Center
Saltmarsh, David
2009-01-01
In 2004 the Australia Council of Deans of Education (ACDE) released a report entitled "New teaching, new learning: A vision for Australian education". This report was prepared on behalf of the ACDE by Mary Kalantzis and Andrew Harvey, respectively the President and Executive Officer of the ACDE. The argument put forward in the report is…
Zamir, Ehud; Kong, George Y.X.; Kowalski, Tanya; Coote, Michael; Ang, Ghee Soon
2016-01-01
Purpose We hypothesize that: (1) Anterior chamber depth (ACD) is correlated with the relative anteroposterior position of the pupillary image, as viewed from the temporal side. (2) Such a correlation may be used as a simple quantitative tool for estimation of ACD. Methods Two hundred sixty-six phakic eyes had lateral digital photographs taken from the temporal side, perpendicular to the visual axis, and underwent optical biometry (Nidek AL scanner). The relative anteroposterior position of the pupillary image was expressed using the ratio between: (1) lateral photographic temporal limbus to pupil distance (“E”) and (2) lateral photographic temporal limbus to cornea distance (“Z”). In the first chronological half of patients (Correlation Series), E:Z ratio (EZR) was correlated with optical biometric ACD. The correlation equation was then used to predict ACD in the second half of patients (Prediction Series) and compared to their biometric ACD for agreement analysis. Results A strong linear correlation was found between EZR and ACD, R = −0.91, R2 = 0.81. Bland-Altman analysis showed good agreement between predicted ACD using this method and the optical biometric ACD. The mean error was −0.013 mm (range −0.377 to 0.336 mm), standard deviation 0.166 mm. The 95% limits of agreement were ±0.33 mm. Conclusions Lateral digital photography and EZR calculation is a novel method to quantitatively estimate ACD, requiring minimal equipment and training. Translational Relevance EZ ratio may be employed in screening for angle closure glaucoma. It may also be helpful in outpatient medical clinic settings, where doctors need to judge the safety of topical or systemic pupil-dilating medications versus their risk of triggering acute angle closure glaucoma. Similarly, non ophthalmologists may use it to estimate the likelihood of acute angle closure glaucoma in emergency presentations. PMID:27540496
Mösler, M P; Werner, J U; Lang, G K
2015-07-01
In glaucoma the structures of the anterior chamber are important for classification, therapy, progression and prognosis. In this context anterior segment optical coherence tomography (AS-OCT) gains more relevance. This study compares AS-OCT with gonioscopy in diagnostic performance of chamber angle (CA) assessment. 104 consecutive subjects with glaucoma underwent AS-OCT imaging using the Visante OCT. RESULTS were compared to gonioscopic grading from patient history using the Shaffer system. In addition, anterior chamber depth (ACD) assessment using slitlamp examination was evaluated as a prognostic factor for chamber angle width (CAW) and verified by AS-OCT measurement. Average CAW was 29° (AS-OCT). 17 % of the CAs that were "wide" in gonioscopy (variance 5-55°), showed a "narrow" CA in AS-OCT. 35 % of the CAs that were "narrow" in gonioscopy (variance 0-39°) showed a "wide" CA in AS-OCT. ACD assessment using slitlamp examination is a good predictor for CAW. In this context the technique provides equal informative value as gonioscopy. In cases of "wide" ACDs it is even superior. The critical ACD for an increased risk of angle closure is 2.4 mm. Concerning the critical ACD (< 2.4 mm) the technique gave the possibility to estimate, whether the patients were in the crucial range or not. Average ACD was 2.7 mm (AS-OCT). A strong correlation (correlation coefficient 0.83) between ACD and CAW was observed. Variation of 1 mm in the ACD leads to a change of 18.9° in the CAW. All patients with angle closure glaucoma were below this threshold and 74 % of patients with critical ACD had "narrow" (AS-OCT) CAs. In the case of routine clinical practice with inexperienced residents or circumstances that make gonioscopy difficult or impossible, optical coherence tomography is an effective alternative to the gold standard and is to some extent even superior. Georg Thieme Verlag KG Stuttgart · New York.
Quality of life in patients with allergic contact dermatitis.
Kadyk, Deana L; McCarter, Kevin; Achen, Fritz; Belsito, Donald V
2003-12-01
Allergic contact dermatitis (ACD), a common dermatological disorder, often results in ongoing disease and disability. However, relatively little has been published quantifying the quality of life (QoL) of patients with ACD. This study was conducted to investigate the impact of ACD on QoL and explore prognostic factors that influence outcomes. A total of 428 subjects with ACD were, at varying times after diagnosis, mailed a QoL questionnaire modified from Skindex-16 to include an additional 5 items pertaining to occupational impact. The QoL scores were correlated with subject demographics, disease characteristics, and management techniques to ascertain factors that impact QoL in subjects with ACD. The response rate was 35%, with 149 subjects returning the postal survey. Responders reported being bothered most by itching, skin irritation, and persistence of the condition. Of the four scales included in the QoL questionnaire, the emotions scale had the worst composite QoL score, followed by symptoms, functioning, and occupational impact. Patients with ACD of the face were significantly more bothered by the appearance of their skin. Hand involvement and occupationally related ACD were associated with worse QoL scores within the occupational impact and functioning scales. Subjects that had changed jobs because of ACD had more severe QoL impairment than any other group analyzed, with significantly worse scores on 17 of the 21 QoL items. A history of atopic eczema seemed to impart improved outcomes on patients with ACD, and these subjects were less worried about being fired from their jobs. Subjects diagnosed by patch testing more than 36 months after disease onset seemed to have worse QoL scores than those diagnosed earlier in the natural history of the disease. Patients diagnosed by patch testing within the last 6 months had the worst QoL scores, while the best outcomes were reported in subjects patch tested 6 to 12 months ago. A slight decline in QoL was observed 12 months after patch testing, but scores did not diminish back to the level seen immediately after diagnosis. ACD has an appreciable effect on QoL, especially when it affects the hands, the face, or is occupationally related. Of the four scales included in our study, the emotions scale suffered the greatest effect. Emotional impact is therefore an important measure of QoL in ACD patients. Outcomes in patients with ACD were improved by early diagnosis and subjects enjoyed their best QoL at 6 to 12 months after patch testing. However, individuals who elected to change jobs because of their skin condition reported significantly worse QoL than those who retained their current positions.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-01
... Committee to the Director (ACD), Centers for Disease Control and Prevention--Ethics Subcommittee (ES) In... to the ACD, CDC, regarding a broad range of public health ethics questions and issues arising from... address public health ethics issues and coordination of these efforts with the CDC Office of State, Tribal...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-08
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... provide counsel to the ACD, CDC, regarding a broad range of public health ethics questions and issues... in their efforts to address public health ethics challenges. The agenda is subject to change as...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-17
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... will provide counsel to the ACD, CDC, regarding a broad range of public health ethics questions and...; efforts to support state, tribal, local and territorial health departments address ethical issues in the...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-11
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--National Biosurveillance.... L. 92-463), the CDC announces the following meeting of aforementioned subcommittee: Time and Date: 8.... Purpose: As a subcommittee to the CDC's ACD, the NBAS will provide counsel to the CDC and the Federal...
Controls over aboveground forest carbon density on Barro Colorado Island, Panama
NASA Astrophysics Data System (ADS)
Mascaro, J.; Asner, G. P.; Muller-Landau, H. C.; van Breugel, M.; Hall, J.; Dahlin, K.
2010-12-01
Despite the importance of tropical forests to the global carbon cycle, ecological controls over landscape-level variation in live aboveground carbon density (ACD) in tropical forests are poorly understood. Here, we conducted a spatially comprehensive analysis of ACD variation for a mainland tropical forest - Barro Colorado Island, Panama (BCI) - and tested site factors that may control such variation. We mapped ACD over 98% of BCI (~1500 ha) using airborne Light Detection and Ranging (LiDAR), which was well-correlated with ground-based measurements of ACD in Panamanian forests of various ages (r2 = 0.77, RMSE = 29 Mg C ha-1, P < 0.0001). We used multiple regression to examine controls over LiDAR-derived ACD, including slope angle, bedrock, soil texture, and forest age. Collectively, these variables explained 14% of the variation in ACD at 30-m resolution, and explained 33% at 100-m resolution. At all resolutions, slope (linked to underlying bedrock variation) was the strongest driving factor; standing carbon stocks were generally higher on steeper slopes, where erosion rates tend to exceed weathering rates, compared to gentle slopes, where weathering in place produces deep, oxic soils. This result suggests that physiography may be more important in controlling ACD variation in Neotropical forests than currently thought. Although BCI has been largely undisturbed by humans for a century, past land-use over approximately half of the island still influences ACD variation, with younger forests (80-130 years old) averaging ~15% less carbon storage than old-growth forests (>400 years old). If other regions of relatively old tropical secondary forests also store less carbon aboveground than primary forests, the effects on the global carbon cycle could be substantial and difficult to detect with satellite monitoring.
Development and characterization of an allergoid of cat dander for immunotherapy.
Sola, J P; Pedreño, Y; Cerezo, A; Peñalver-Mellado, M
2018-01-13
Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice. The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD was characterized in protein profile by SDS-PAGE, size exclusion chromatography (SEC) and peptide footprint. The allergenic profile of ACD was determined by immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen content in NCD was obtained by the ELISA sandwich protocol and was extrapolated to ACD. The control process determined the optimal development of the allergoid. The ACD obtained contains 182.28μg/mg of protein and 11.90μg/mg of Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel d 7. The high degree of polymerization was evidenced with the determination of the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD showed a significant loss of allergenicity respect to NCD, while the IgG-binding capacity was maintained. The ACD obtained presents a good safety profile, so would be a good alternative for treatment of cat allergy. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.
Tian, Sheng; Li, Youyong; Wang, Junmei; Xu, Xiaojie; Xu, Lei; Wang, Xiaohong; Chen, Lei; Hou, Tingjun
2013-01-21
In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.
2013-01-01
Background In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. Results First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. Conclusion The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design. PMID:23336706
Performance of the Anti-Coincidence Detector on the GLAST Large Area Telescope
NASA Technical Reports Server (NTRS)
Thompson, D. J.; Charles, E.; Hartman, R. C.; Moiseev, A. A.; Ormes, J. F.
2007-01-01
The Anti-Coincidence Detector (ACD), the outermost detector layer in the Gamma-ray Large Area Space Telescope (GLAST) Large Area Telescope (LAT), is designed to detect and veto incident cosmic ray charged particles, which outnumber cosmic gamma rays by 3-4 orders of magnitude. The challenge in ACD design is that it must have high (0.9997) detection efficiency for singly-charged relativistic particles, but must also have a low probability for self-veto of high-energy gammas by backplash radiation from interactions in the LAT calorimeter. Simulations and tests demonstrate that the ACD meete its design requirements. The performance of the ACD has remained stable thrugh stand-alone environmental testing, shipment across the U.S. installation onto the LAT, shipment back across the U.S., LAT environmental testing, and shipment to Arizona. As part of the fully-assembled GLAST observatory, the ACD is being readied for final testing before launch.
Bilateral Adventitial Cystic Disease of the Popliteal Artery: A Case Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ortiz M, William R.; Lopera, Jorge E., E-mail: Jorge.lopera@utsouthwestern.edu; Gimenez, Carlos R.
2006-04-15
Adventitial cystic disease (ACD) of the popliteal artery is an uncommon vascular condition of unknown etiology. In the present case report, we describe a case of bilateral ACD of the popliteal artery in a 58-year-old male. To the best of our knowledge, this is the first case of bilateral ACD of the popliteal artery reported in the literature.
Luckett, Tim; Bhattarai, Priyanka; Phillips, Jane; Agar, Meera; Currow, David; Krastev, Yordanka; Davidson, Patricia M
2015-11-01
A drive to promote advance care planning at a population level has led to a proliferation of online advance care directive (ACD) templates but little information to guide consumer choice. The current study aimed to appraise the quality of online ACD templates promoted for use in Australia. A systematic review of online Australian ACD templates was conducted in February 2014. ACD templates were identified via Google searches, and quality was independently appraised by two reviewers against criteria from the 2011 report A National Frameworkfor Advance Care Directives. Bias either towards or against future medical treatment was assessed using criteria designed to limit subjectivity. Fourteen online ACD templates were included, all of which were available only in English. Templates developed by Southern Cross University best met the framework criteria. One ACD template was found to be biased against medical treatment--the Dying with Dignity Victoria Advance Healthcare Directive. More research is needed to understand how online resources can optimally elicit and record consumers' individual preferences for future care. Future iterations of the framework should address online availability and provide a simple rating system to inform choice and drive quality improvement.
Structural insight into the TFIIE–TFIIH interaction: TFIIE and p53 share the binding region on TFIIH
Okuda, Masahiko; Tanaka, Aki; Satoh, Manami; Mizuta, Shoko; Takazawa, Manabu; Ohkuma, Yoshiaki; Nishimura, Yoshifumi
2008-01-01
RNA polymerase II and general transcription factors (GTFs) assemble on a promoter to form a transcription preinitiation complex (PIC). Among the GTFs, TFIIE recruits TFIIH to complete the PIC formation and regulates enzymatic activities of TFIIH. However, the mode of binding between TFIIE and TFIIH is poorly understood. Here, we demonstrate the specific binding of the C-terminal acidic domain (AC-D) of the human TFIIEα subunit to the pleckstrin homology domain (PH-D) of the human TFIIH p62 subunit and describe the solution structures of the free and PH-D-bound forms of AC-D. Although the flexible N-terminal acidic tail from AC-D wraps around PH-D, the core domain of AC-D also interacts with PH-D. AC-D employs an entirely novel binding mode, which differs from the amphipathic helix method used by many transcriptional activators. So the binding surface between PH-D and AC-D is much broader than the specific binding surface between PH-D and the p53 acidic fragments. From our in vitro studies, we demonstrate that this interaction could be a switch to replace p53 with TFIIE on TFIIH in transcription. PMID:18354501
Structural basis for NKG2A/CD94 recognition of HLA-E
Kaiser, Brett K.; Pizarro, Juan Carlos; Kerns, Julie; Strong, Roland K.
2008-01-01
The NKG2x/CD94 (x = A, C, E) natural killer-cell receptors perform an important role in immunosurveillance by binding to HLA-E complexes that exclusively present peptides derived from MHC class I leader sequences, thereby monitoring MHC class I expression. We have determined the crystal structure of the NKG2A/CD94/HLA-E complex at 4.4-Å resolution, revealing two critical aspects of this interaction. First, the C-terminal region of the peptide, which displays the most variability among class I leader sequences, interacts entirely with CD94, the invariant component of these receptors. Second, residues 167–170 of NKG2A/C account for the ≈6-fold-higher affinity of the inhibitory NKG2A/CD94 receptor compared to its activating NKG2C/CD94 counterpart. These residues do not contact HLA-E or peptide directly but instead form part of the heterodimer interface with CD94. An evolutionary analysis across primates reveals that whereas CD94 is evolving under purifying selection, both NKG2A and NKG2C are evolving under positive selection. Specifically, residues at the CD94 interface have evolved under positive selection, suggesting that the evolution of these genes is driven by an interaction with pathogen-derived ligands. Consistent with this possibility, we show that NKG2C/CD94, but not NKG2A/CD94, weakly but specifically binds to the CMV MHC-homologue UL18. Thus, the evolution of the NKG2x/CD94 family of receptors has likely been shaped both by the need to bind the invariant HLA-E ligand and the need to avoid subversion by pathogen-derived decoys. PMID:18448674
NASA Astrophysics Data System (ADS)
Hua, Jinsong; Rudshaug, Magne; Droste, Christian; Jorgensen, Robert; Giskeodegard, Nils-Haavard
2018-06-01
A computational fluid dynamics based multiphase magnetohydrodynamic (MHD) flow model for simulating the melt flow and bath-metal interface deformation in realistic aluminum reduction cells is presented. The model accounts for the complex physics of the MHD problem in aluminum reduction cells by coupling two immiscible fluids, electromagnetic field, Lorentz force, flow turbulence, and complex cell geometry with large length scale. Especially, the deformation of bath-metal interface is tracked directly in the simulation, and the condition of constant anode-cathode distance (ACD) is maintained by moving anode bottom dynamically with the deforming bath-metal interface. The metal pad deformation and melt flow predicted by the current model are compared to the predictions using a simplified model where the bath-metal interface is assumed flat. The effects of the induced electric current due to fluid flow and the magnetic field due to the interior cell current on the metal pad deformation and melt flow are investigated. The presented model extends the conventional simplified box model by including detailed cell geometry such as the ledge profile and all channels (side, central, and cross-channels). The simulations show the model sensitivity to different side ledge profiles and the cross-channel width by comparing the predicted melt flow and metal pad heaving. In addition, the model dependencies upon the reduction cell operation conditions such as ACD, current distribution on cathode surface and open/closed channel top, are discussed.
Park, Dong Ki; Lee, Yang Gi; Park, Hye-Jin
2013-01-01
Rhus verniciflua Stokes (RV) has traditionally been used as a food supplement and a traditional herbal medicine for centuries in Korea. Recent studies suggest that RV has potent antioxidative, antitumor, and anti-inflammatory properties. In this study, the anti-inflammatory effects of RV from mice sensitized with 2,4-dinitrofluorobenzene (DNFB) and activated macrophages were investigated. The results showed that RV reduced ear swelling and hyperplasia of ear tissue as well as an increase in vascular permeability, which are characteristics of allergic contact dermatitis (ACD) with evident histomorphological changes in epidermis and dermis. Decreased numbers of infiltrated mast cells were seen in RV extract treated group, using toluidine blue staining. RV extract significantly regulates the expression of inducible nitric oxide synthase (iNOS) at the translational level in activated macrophages. Furthermore, RV extract and its active compound, fisetin, attenuated the level of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) mRNA in LPS-stimulated macrophages. Anti-ACD effect of RV extract may be due to the suppression of iNOS and proinflammatory cytokines which might be mediated via the NFκB signaling pathways. Collectively, RV extract has potential for alleviating ACD-like symptoms induced by DNFB in the mouse. PMID:23710240
Steward, N; Kusano, T; Sano, H
2000-09-01
A cDNA fragment encoding part of a DNA methyltransferase was isolated from maize. The putative amino acid sequence identically matched that deduced from a genomic sequence in the database (accession no. AF063403), and the corresponding gene was designated as ZmMET1. Bacterially expressed ZmMET1 actively methylated DNA in vitro. Transcripts of ZmMET1 could be shown to exclusively accumulate in actively proliferating cells of the meristems of mesocotyls and root apices, suggesting ZmMET1 expression to be associated with DNA replication. This was confirmed by simultaneous decrease of transcripts of ZmMET1 and histone H3, a marker for DNA replication, in seedlings exposed to wounding, desiccation and salinity, all of which suppress cell division. Cold stress also depressed both transcripts in root tissues. In contrast, however, accumulation of ZmMET1 transcripts in shoot mesocotyls was not affected by cold stress, whereas those for H3 sharply decreased. Such a differential accumulation of ZmMET1 transcripts was consistent with ZmMET1 protein levels as revealed by western blotting. Expression of ZmMET1 is thus coexistent, but not completely dependent on DNA replication. Southern hybridization analysis with a methylation-sensitive restriction enzyme revealed that cold treatment induced demethylation of DNA in the Ac/Ds transposon region, but not in other genes, and that such demethylation primarily occurred in roots. These results suggested that the methylation level was decreased selectively by cold treatment, and that ZmMET1 may, at least partly, prevent such demethylation.
Design and Characteristics of the Anticoincidence Detector for the GLAST Large Area Telescope
NASA Technical Reports Server (NTRS)
Moiseev, A. A.; Hartman, R. C.; Johnson, T. E.; Ormes, J. F.; Thompson, D. J.
2005-01-01
The Anti-Coincidence Detector (ACD) is the outermost detector layer in the GLAST Large Area Telescope (LAT), surrounding the top and sides of the tracker. The purpose of the ACD is to detect and veto incident cosmic ray charged particles, which outnumber cosmic gamma rays by 3-4 orders of magnitude. The challenge in ACD design is that it must have high (0.9997) detection efficiency for singly charged relativistic particles, but must also have low sensitivity to backsplash particles. These are products of high- energy interactions in the LAT calorimeter. They can cause a veto signal in the ACD, resulting in loss of good gamma-ray events.
Comparison of adaptive critic-based and classical wide-area controllers for power systems.
Ray, Swakshar; Venayagamoorthy, Ganesh Kumar; Chaudhuri, Balarko; Majumder, Rajat
2008-08-01
An adaptive critic design (ACD)-based damping controller is developed for a thyristor-controlled series capacitor (TCSC) installed in a power system with multiple poorly damped interarea modes. The performance of this ACD computational intelligence-based method is compared with two classical techniques, which are observer-based state-feedback (SF) control and linear matrix inequality LMI-H(infinity) robust control. Remote measurements are used as feedback signals to the wide-area damping controller for modulating the compensation of the TCSC. The classical methods use a linearized model of the system whereas the ACD method is purely measurement-based, leading to a nonlinear controller with fixed parameters. A comparative analysis of the controllers' performances is carried out under different disturbance scenarios. The ACD-based design has shown promising performance with very little knowledge of the system compared to classical model-based controllers. This paper also discusses the advantages and disadvantages of ACDs, SF, and LMI-H(infinity).
The HEAO experience - design through operations
NASA Technical Reports Server (NTRS)
Hoffman, D. P.
1983-01-01
The design process and performance of the NASA High Energy Astronomy Observatories (HEAO-1, 2, and 3) are surveyed from the initiation of the program in 1968 through the end of HEAO-3 operation in May, 1981, with a focus on the attitude control and determination subsystem (ACDS). The science objectives, original and revised overall design concepts, final design for each spacecraft, and details of the ACDS designs are discussed, and the stages of the ACDS design process, including redefinition to achieve 50 percent cost reduction, detailed design of common and mission-unique hardware and software, unit qualification, subsystem integration, and observatory-level testing, are described. Overall and ACDS performance is evaluated for each mission and found to meet or exceed design requirements despite some difficulties arising from errors in startracker-ACDS-interface coordination and from gyroscope failures. These difficulties were resolved by using the flexibility of the software design. The implicationns of the HEAO experience for the design process of future spacecraft are suggested.
Online learning control using adaptive critic designs with sparse kernel machines.
Xu, Xin; Hou, Zhongsheng; Lian, Chuanqiang; He, Haibo
2013-05-01
In the past decade, adaptive critic designs (ACDs), including heuristic dynamic programming (HDP), dual heuristic programming (DHP), and their action-dependent ones, have been widely studied to realize online learning control of dynamical systems. However, because neural networks with manually designed features are commonly used to deal with continuous state and action spaces, the generalization capability and learning efficiency of previous ACDs still need to be improved. In this paper, a novel framework of ACDs with sparse kernel machines is presented by integrating kernel methods into the critic of ACDs. To improve the generalization capability as well as the computational efficiency of kernel machines, a sparsification method based on the approximately linear dependence analysis is used. Using the sparse kernel machines, two kernel-based ACD algorithms, that is, kernel HDP (KHDP) and kernel DHP (KDHP), are proposed and their performance is analyzed both theoretically and empirically. Because of the representation learning and generalization capability of sparse kernel machines, KHDP and KDHP can obtain much better performance than previous HDP and DHP with manually designed neural networks. Simulation and experimental results of two nonlinear control problems, that is, a continuous-action inverted pendulum problem and a ball and plate control problem, demonstrate the effectiveness of the proposed kernel ACD methods.
Short-term effects of intravitreal bevacizumab on cornea and anterior chamber.
Güler, Mete; Capkın, Musa; Simşek, Ali; Bilak, Semsettin; Bilgin, Burak; Hakim Reyhan, Ali; Fırat, Müge
2014-10-01
To determine the short-term effects of single-dose intravitreal bevacizumab injection on central corneal thickness (CCT), simulated keratometry (Sim K), anterior chamber depth (ACD), iridocorneal angle (ICA) and intraocular pressure (IOP) measurements. Prospective, nonrandomized, interventional clinical trial. Forty-three eyes of 43 patients aged between 41 and 78 years (average 62 ± 13 years) received an intravitreal injection of 2.5 mg/0.1 mL bevacizumab. Patients who had not undergone additional intravitreal anti-vascular endothelial growth factor therapy within 6 months were included in the study. CCT, Sim K, ACD and ICA measurements were obtained with Sirius Topographer. IOP measurements were taken after topographic measurements with Goldmann applanation tonometer. The CCT, ACD, ICA and IOP measurements were taken before and after 3rd, 15th days and 1st month of intravitreal bevacizumab injection. Pre- and postinjection of 3rd, 15th days and 1st month CCT (p = 0.999), Sim K (p = 0.746), ACD (p = 0.996), ICA (p = 0.632) and IOP (p = 0.707) measurements were not statistically different. Mean CCT (p = 1.000), Sim K (0.972), ACD (p = 0.998), ICA (0.667) and IOP (0.951) values were similar before and after 3rd day of bevacizumab injection. Mean CCT (p = 0.999), Sim K (p = 0.994), ACD (p = 1.000), ICA (p = 0.999) and IOP (p = 1.000) measurements were also similar before and after 15th day of injection. Preinjection and 1st month of postinjection CCT (p = 0.999), Sim K (p = 0.932), ACD (p = 0.998), ICA (p = 1.000) and IOP (p = 0.741) measurements did not change significantly. Single-dose intravitreal bevacizumab injection does not affect CCT, Sim K, ACD, ICA and IOP in short-term period.
Al-Farhan, Haya M; AlMutairi, Reem N
2013-01-01
Purpose To compare the precision of anterior chamber angle (ACA) and anterior chamber depth (ACD) measurements taken with ultrasound biomicroscopy (UBM) and the Artemis-2 Very High Frequency Ultrasound Scanner (VHFUS) in normal subjects. Design Prospective study. Methods We randomly selected one eye from each of 59 normal subjects in this study. Two subjects dropped out of the study; the associated data were excluded from analysis. ACA and ACD measurements were obtained using the VHFUS and the UBM. The results were compared statistically using repeated-measures analysis of variance for the intraobserver repeatability, unpaired t-test, and limits of agreement. Results The average ACA values for the UBM and the VHFUS (±standard deviation) were 41.83° ± 5.03° and 33.36° ± 6.03°, respectively. The average ACD values were 2.96 ± 0.34 mm and 2.87 ± 0.31 mm. The intraobserver repeatability analysis of variance P-values for ACA and ACD measurements using UBM were 0.10 and 0.68, respectively; for the Artemis-2 VHFUS, the respective values were 0.68 and 0.09. The difference in ACA measurements was statistically significant (t = 8.41; P < 0.0001), while the difference in ACD values was not (t = 1.51; P < 0.13). The mean ACA difference was 8.50° ± 2.50°, and the limits of agreement were +13.30° to −3.60°. The mean ACD difference was 0.09 ± 0.27 mm, and the limits of agreement ranged from 0.61 mm to −0.43 mm. The mean difference percentage of ACD was 3.1% for both instruments. Conclusion In case of the ACD, both instruments can be used interchangeably; however, with the ACA instruments, they cannot be used interchangeably. PMID:23345968
Li, Lin-Feng; Guo, Jing; Wang, Jing
2004-07-01
Environmental contact factors in eczema were investigated in China by clinical questionnaire and patch testing patients with a modified European standard series of allergens. 217 consecutive eczema patients were studied. Contact dermatitis (CD) was clinically diagnosed in 30% of the patients. Among the patients patch tested, 46 patients had clinically diagnosed allergic CD (ACD), 20 patients clinically had non-ACD (NACD) (including 16 cases of irritant contact dermatitis, 1 case of phototoxic contact reaction and 3 cases of asteatotic eczema) and 115 patients had clinically suspected ACD. 45 patients (98%) in the ACD group went on to have relevant patch test results. The most common ACD was from metals, fragrance materials, cosmetics and rubber materials. The most common contact allergens identified were nickel, fragrance mix, para-phenylenediamine (PPD), carba mix and thimerosal. No adverse reactions were observed to patch testing, except for pruritus in patch-test-positive patients. The positive rate of patch testing in ACD was much higher than that in NACD (98% versus 15%, P < 0.05, chi(2)-test). 60 (28%) patients had facial dermatitis (FD). Among these, 20 (33%) were confirmed as having ACD. 48 (22%) patients had hand dermatitis (HD). Among these, 7 (15%) were confirmed as having ACD. Fewer patients were confirmed as having ACD in the HD group than in the FD (15% versus 33%, P < 0.05, chi(2)-test). Although the difference was not significant, the total positivity rate in the HD group (55%) was lower than in the other groups. 65 (30%) patients had unclassified endogenous eczema (UEE). The total positive rate of patch testing in the UEE group (56%) was no different from that in the FD or HD groups. However, the relevance of positive patch tests was hard to determine in UEE. These results indicate that CD is common in eczema; relatively more patients with FD have ACD, while other factors, such as irritation, may play more of a role in HD. The total positive rate of patch testing in the UEE group was no different from that in the FD or HD groups, suggesting that patch testing should be stressed in UEE and the relevance of positive patch test results in UEE should be studied further. It is effective and safe to patch eczema patients with a modified European standard series of allergens in China.
Weimann, Andreas; Cremer, Malte; Hernáiz-Driever, Pablo; Zimmermann, Mathias
2016-01-01
The present study was aimed to prove the usefulness of a new diagnostic plot (Hema-Plot), illustrating the relationship between the hemoglobin content of reticulocytes (Ret-He) as a marker of functional iron deficiency and the difference between the reticulocyte and erythrocyte hemoglobin content (Delta-He) as a marker of an impaired hemoglobinization of newly formed reticulocytes occurring during inflammatory processes, to differentiate between various disease-specific types of anemia. A complete blood and reticulocyte count was performed on routine EDTA blood samples from 345 patients with and without various disease-specific types of anemia using the Sysmex XN-9000 hematology analyzer: blood healthy newborns (n = 23), blood healthy adults (n = 31), patients suffering from anemia of chronic disease (ACD) due to diverse oncological, chronic inflammatory, or autoimmune diseases (total n = 138) with (n = 65) and without therapy (n = 73), patients with thalassemia and/or hemoglobinopathy (n = 18), patients with iron deficiency anemia (IDA) (n = 35), patients with a combination of ACD and IDA (n = 17), as well as patients suffering from sepsis (total n = 83) with (n = 32) and without therapy (n = 51). The results for Ret-He, Delta-He, and C-reactive protein (CRP) were statistically compared (Mann-Whitney U Test) between the particular patient groups and the diagnostic plots were drawn. Delta-Hemoglobin showed a statistically significant difference between blood healthy newborns and blood healthy adults (p ≤ 0.05), while Ret-He and C-reactive protein did not. In addition, of all three biomarkers only Delta-He showed a statistically significant difference (p ≤ 0.05) between the ACD/IDA and IDA cohort. Delta-He, Ret-He, and CRP showed a statistically significant difference between patient cohorts with and without therapy suffering from ACD, ACD/IDA, and sepsis before and after medical therapy (p ≤ 0.05). The Hema-Plot illustrated the dynamic character of Ret-He and Delta-He, notably in inflammation-based types of anemia like ACD or ACD/ IDA. Delta-He is a new biomarker clearly distinguishing between inflammation-based types of anemia before and after medical therapy, as well as between ACD/IDA and IDA. The new Hema-Plot is a helpful tool for differential diagnosis and disease-monitoring in various types of disease-specific anemia, especially in ACD and ACD/IDA. The Hema-Plot can be used to identify non-adherent patients or an insufficient therapy.
Hernández-Chirlaque, Cristina; Gámez-Belmonte, Reyes; Ocón, Borja; Martínez-Moya, Patricia; Wirtz, Stefan; Sánchez de Medina, Fermín; Martínez-Augustin, Olga
2017-07-01
Two alkaline phosphatase isoforms, intestinal [IAP] and tissue non-specific alkaline phosphatase [TNAP], are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes, using heterozygous TNAP+/- mice [as TNAP-/- mice are non-viable]. In vitro primary cultures and in vivo T cell models using TNAP+/- mice were used. Stimulated splenocytes [lipopolysaccharide and concanavalin A] and T lymphocytes [concanavalin A and a-CD3/a-CD28] showed a decreased cytokine production and expression when compared with wild-type [WT] cells. Decreased T cell activation was reproduced by the TNAP inhibitors levamisole, theophylline, and phenylalanine in WT cells. Intraperitoneal administration of anti-CD3 in vivo resulted in reduced plasma cytokine levels, and decreased activation of splenocytes and T cells ex vivo in TNAP+/- mice. We further tested the hypothesis that TNAP expressed in T lymphocytes is involved in T cell activation and inflammation, using the lymphocyte transfer model of colitis. Rag1-/- mice were transferred with T naïve cells [CD4+ CD62L+] from TNAP+/- or WT mice and developed colitis, which was attenuated in the group receiving TNAP+/- cells. Compared with WT, T cells from TNAP+/- mice showed a decreased capacity for proliferation, with no change in differentiation. Our results offer clear evidence that TNAP modulates T lymphocyte function and specifically T cell-dependent colitis. This was associated with distinct changes in the type of TNAP expressed, probably because of changes in glycosylation. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
Mathematical modeling of flow in the working part of an acousto-convective drying system
NASA Astrophysics Data System (ADS)
Kravchenko, A. S.; Zhilin, A. A.; Fedorova, N. N.
2018-03-01
The objective of this study was to numerically simulate the nonstationary processes occurring in the acoustic-convective dryer (ACD) channel. In the present work, the problem was solved numerically in a three-dimensional formulation taking into account all features of the ACD duct in real geometry. The processes occurring in the ACD duct were simulated using the ANSYS Fluent 18.0 software. The numerical experiments provided an aggregate picture of the working gas flow in the ACD duct with the features near the subsonic nozzle and the cavity. The results of the numerical calculations were compared with experimental data. The best agreement with the experimental data was obtained for the viscosity model neglecting turbulent effects.
Association of Anticholinergic Drug Use With Risk for Late Age-Related Macular Degeneration.
Aldebert, Gauthier; Faillie, Jean-Luc; Hillaire-Buys, Dominique; Mura, Thibault; Carrière, Isabelle; Delcourt, Cécile; Creuzot-Garcher, Catherine; Villain, Max; Daien, Vincent
2018-05-24
Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Association between exposure to ACDs and late AMD. Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.
The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment.
Leonard, Alexandra; Guttman-Yassky, Emma
2018-05-12
Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.
Liu, Boyi; Tai, Yan; Achanta, Satyanarayana; Kaelberer, Melanie M.; Caceres, Ana I.; Shao, Xiaomei; Fang, Jianqiao; Jordt, Sven-Eric
2016-01-01
Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO2. Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD. PMID:27821781
Liu, Boyi; Tai, Yan; Achanta, Satyanarayana; Kaelberer, Melanie M; Caceres, Ana I; Shao, Xiaomei; Fang, Jianqiao; Jordt, Sven-Eric
2016-11-22
Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.
Royston, Patrick; Sauerbrei, Willi
2016-01-01
In a recent article, Royston (2015, Stata Journal 15: 275-291) introduced the approximate cumulative distribution (acd) transformation of a continuous covariate x as a route toward modeling a sigmoid relationship between x and an outcome variable. In this article, we extend the approach to multivariable modeling by modifying the standard Stata program mfp. The result is a new program, mfpa, that has all the features of mfp plus the ability to fit a new model for user-selected covariates that we call fp1( p 1 , p 2 ). The fp1( p 1 , p 2 ) model comprises the best-fitting combination of a dimension-one fractional polynomial (fp1) function of x and an fp1 function of acd ( x ). We describe a new model-selection algorithm called function-selection procedure with acd transformation, which uses significance testing to attempt to simplify an fp1( p 1 , p 2 ) model to a submodel, an fp1 or linear model in x or in acd ( x ). The function-selection procedure with acd transformation is related in concept to the fsp (fp function-selection procedure), which is an integral part of mfp and which is used to simplify a dimension-two (fp2) function. We describe the mfpa command and give univariable and multivariable examples with real data to demonstrate its use.
Terio, K A; Munson, L; Moore, P F
2012-09-01
Captive cheetahs have an unusually severe progressive gastritis that is not present in wild cheetahs infected with the same strains of Helicobacter. This gastritis, when severe, has florid lymphocyte and plasma cell infiltrates in the epithelium and lamina propria with gland destruction, parietal cell loss, and, in some cases, lymphoid follicles. The local gastric immune response was characterized by immunohistochemistry in 21 cheetahs with varying degrees of gastritis. The character of the response was similar among types of gastritis except that cheetahs with severe gastritis had increased numbers (up to 70%) of lamina proprial CD79a+CD21- B cells. CD3+CD4+ T cells were present in the lamina propria, and CD3+CD8α+ T cells were within the glandular epithelium. Lymphoid aggregates had follicular differentiation with a central core of CD79a+/CD45R+ B cells and with an outer zone of CD3+ T cells that expressed both CD4 and CD8 antigens. MHC II antigens were diffusely expressed throughout the glandular and superficial epithelium. No cheetah had evidence of autoantibodies against the gastric mucosa when gastric samples from 30 cheetahs with different degrees of gastritis were incubated with autologous and heterologous serum. These findings indicate that T-cell distribution in cheetahs is qualitatively similar to that in other species infected with Helicobacter but that large numbers of lamina propria activated B cells and plasma cells did distinguish cheetahs with severe gastritis. Further research is needed to determine whether alterations in the Th1:Th2 balance are the cause of this more plasmacytic response in some cheetahs.
Sasakawa, S; Tokunaga, E; Hasegawa, G; Nakagawa, S
1977-09-01
The coil planet centrifuge (CPC) can be used to measure the osmotic fragility of erythrocytes. Fragility measured by this method alters when different salts are used. The CPC and Parpart methods were used to measure the changes during storage in red cell osmotic fragility in ACD or CPD blood with or without adenine. More marked changes were detected by the CPC method, especially in old cells. The changes of fragility of erythrocytes during storage seem to occur mainly in old cells. Adenine is effective in preventing such changes.
Nezafati, Kaveh A; Carroll, Bryan; Storrs, Frances J; Cruz, Ponciano D
2013-01-01
The American Contact Dermatitis Society (ACDS) is the principal organization representing the subspecialty of contact dermatitis in the United States. The aim of this study was to characterize ACDS members with respect to demographic characteristics, patch-test practices, and sentiments regarding the Society and its journal Dermatitis. We conducted cross-sectional postal and online surveys of ACDS members. More than a third of ACDS members responded to the survey, 92% of whom practice dermatology, and most of whom are community practitioners. Responders manage patients with allergic and irritant dermatitis at a similar frequency. On average, they patch test 4 patients per week using 66 allergens per patient, which often include customized trays. Almost half of these practitioners learned patch testing from their residency programs. Most of the responders read and value the Society journal, value the Contact Allergen Management Program database, and attend society meetings. The ACDS is comprised overwhelmingly of dermatologists who are primarily community-based, young relative to the start of their practices, and use the Society's resources for continuing education.
Inhibition of murine DNA methyltransferase Dnmt3a by DNA duplexes containing pyrimidine-2(1H)-one.
Cherepanova, N A; Zhuze, A L; Gromova, E S
2010-09-01
Here we studied the inhibition of the catalytic domain of Dnmt3a methyltransferase (Dnmt3a-CD) by DNA duplexes containing the mechanism-based inhibitor pyrimidine-2(1H)-one (P) instead of the target cytosine. It has been shown that conjugates of Dnmt3a-CD with P-DNA (DNA containing pyrimidine-2(1H)-one) are not stable to heating at 65°C in 0.1% SDS. The yield of covalent intermediate increases in the presence of the regulatory factor Dnmt3L. The importance of the DNA minor groove for covalent intermediate formation during the methylation reaction catalyzed by Dnmt3a-CD has been revealed. P-DNA was shown to inhibit Dnmt3a-CD; the IC(50) is 830 nM. The competitive mechanism of inhibition of Dnmt3a-CD by P-DNA has been elucidated. It is suggested that therapeutic effect of zebularine could be achieved by inhibition of not only Dnmt1 but also Dnmt3a.
Schell-Apacik, Chayim; Hardt, Michael; Ertl-Wagner, Birgit; Klopocki, Eva; Möhrenschlager, Matthias; Heinrich, Uwe; von Voss, Hubertus
2008-09-01
Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.
Campanoni, Prisca; Nick, Peter
2005-01-01
During exponential phase, the tobacco (Nicotiana tabacum) cell line cv Virginia Bright Italia-0 divides axially to produce linear cell files of distinct polarity. This axial division is controlled by exogenous auxin. We used exponential tobacco cv Virginia Bright Italia-0 cells to dissect early auxin signaling, with cell division and cell elongation as physiological markers. Experiments with 1-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D) demonstrated that these 2 auxin species affect cell division and cell elongation differentially; NAA stimulates cell elongation at concentrations that are much lower than those required to stimulate cell division. In contrast, 2,4-D promotes cell division but not cell elongation. Pertussis toxin, a blocker of heterotrimeric G-proteins, inhibits the stimulation of cell division by 2,4-D but does not affect cell elongation. Aluminum tetrafluoride, an activator of the G-proteins, can induce cell division at NAA concentrations that are not permissive for division and even in the absence of any exogenous auxin. The data are discussed in a model where the two different auxins activate two different pathways for the control of cell division and cell elongation. PMID:15734918
Effect of sodium citrate based anticoagulants on the growth activity of malaria parasites.
Liu, Zhong-xiang; Wang, Xian-feng; Li, Shu-mei; Li, Xun; Xue, Cai-fang; Miao, Jun
2004-12-01
To study the effect of anticoagulants based on sodium citrate on the growth activity of malaria parasites. The parasites were treated with 3 anticoagulants (ACD, CD and SC), respectively, and the parasitemia was determined to measure the effect of the anticoagulants on the growth of the parasites. Unsynchronized Plasmodium falciparum was treated with the anticoagulants at different concentrations for 3 h at 37 degrees C. Treated erythrocytes were mixed with normal parasites or treated parasites with normal erythrocytes, which was followed by parasitemia determination of the two cultures to determine the cell target of the anticoagulants. Stage-synchronized parasites (ring, trophozoite and schizont) were treated as above to investigate the stage target. P. berghei was also treated with anticoagulants and inoculated in mice to detect the effect of anticoagulants on the animal malaria parasite by counting the parasitemia. All 3 anticoagulants inhibited falciparum parasite growth and ACD had the strongest potency. The treatments of the erythrocyte and the parasite with anticoagulants respectively showed that the anticoagulants targeted the parasites rather than normal erythrocytes. Stage-synchronized parasite treatment suggested anticoagulants primarily inhibited schizonts. The effect of anticoagulants on P. berghei was similar to that on P. falciparum. ACD showed the most significant inhibitive effect on the growth of malaria parasites and SC was the best anticoagulant based on sodium citrate for malarial experiments.
Oriented cell division: new roles in guiding skin wound repair and regeneration
Yang, Shaowei; Ma, Kui; Geng, Zhijun; Sun, Xiaoyan; Fu, Xiaobing
2015-01-01
Tissue morphogenesis depends on precise regulation and timely co-ordination of cell division and also on the control of the direction of cell division. Establishment of polarity division axis, correct alignment of the mitotic spindle, segregation of fate determinants equally or unequally between daughter cells, are essential for the realization of oriented cell division. Furthermore, oriented cell division is regulated by intrinsic cues, extrinsic cues and other cues, such as cell geometry and polarity. However, dysregulation of cell division orientation could lead to abnormal tissue development and function. In the present study, we review recent studies on the molecular mechanism of cell division orientation and explain their new roles in skin repair and regeneration. PMID:26582817
Çağlar, Çağatay; Kocamış, Sücattin İlker; Demir, Emre; Durmuş, Mustafa
2017-06-01
To investigate the accuracy of the measurements of Nidek AL-Scan by comparing with Sirius (CSO, Florence, Italy), a corneal tomography which also employs the Scheimpflug principle, and a commonly used device, ultrasound biometry (UB) (Aviso A/B, Quantel Medical, MT, USA). Right eyes of 85 healthy volunteers (58 women 27 men) with a mean age of 39.24 ± 14.37 years (range 15-68) were enrolled into this comparative prospective study. Average K 2.4, average K 3.3, CCT (central corneal thickness), WTW (white to white distance), ACD (anterior chamber depth) and AL (axial length) were obtained from the AL-Scan and compared with average SimK, CCT, WTW (horizontal anterior chamber diameter) and ACD obtained from Sirius and also compared with ACD and AL obtained from UB. The statistically significant difference was found between all of the measurements (p < 0.001) except the average keratometry values (K2.4, K3.3, SimK) (p = 0.083). There was a perfect correlation between keratometry, CCT and AL measurements of the devices (ICC = 0.977, 0.954, 0.923, respectively) and there was a strong correlation between the WTW measurements of AL-Scan and Sirius (ICC = 0.865). While ACD parameter of AL-Scan and UB showed a perfect correlation (ICC = 0.977), there was a moderate correlation between AL-Scan and Sirius and also between UB and Sirius (ICC = 0.608 and 0.664, respectively). There was a high correlation between the all measurements, besides ACD, of AL-Scan and Sirius and they can be used interchangeably for average keratometry and WTW confidently. However, ACD and CCT have a broader 95 % LoA (-0.039 to 0.744 and -24.985 to 3.691, respectively). In addition, AL-Scan and UB were in good agreement regarding ACD, while differences in AL measurements of UB and AL-Scan were clinically important (95 % LoA = -0.091 to 0.703). Furthermore, UB and Sirius have a moderate agreement regarding ACD (95 % LoA = -0.047 to 0.680).
Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.
Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua
2017-05-01
Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.
NASA Astrophysics Data System (ADS)
Sato, Aki-Hiro
2004-04-01
Autoregressive conditional duration (ACD) processes, which have the potential to be applied to power law distributions of complex systems found in natural science, life science, and social science, are analyzed both numerically and theoretically. An ACD(1) process exhibits the singular second order moment, which suggests that its probability density function (PDF) has a power law tail. It is verified that the PDF of the ACD(1) has a power law tail with an arbitrary exponent depending on a model parameter. On the basis of theory of the random multiplicative process a relation between the model parameter and the power law exponent is theoretically derived. It is confirmed that the relation is valid from numerical simulations. An application of the ACD(1) to intervals between two successive transactions in a foreign currency market is shown.
Sato, Aki-Hiro
2004-04-01
Autoregressive conditional duration (ACD) processes, which have the potential to be applied to power law distributions of complex systems found in natural science, life science, and social science, are analyzed both numerically and theoretically. An ACD(1) process exhibits the singular second order moment, which suggests that its probability density function (PDF) has a power law tail. It is verified that the PDF of the ACD(1) has a power law tail with an arbitrary exponent depending on a model parameter. On the basis of theory of the random multiplicative process a relation between the model parameter and the power law exponent is theoretically derived. It is confirmed that the relation is valid from numerical simulations. An application of the ACD(1) to intervals between two successive transactions in a foreign currency market is shown.
Advance care planning in Australia: what does the law say?
Carter, Rachel Z; Detering, Karen M; Silvester, William; Sutton, Elizabeth
2016-09-01
Advance care planning (ACP) assists people to plan for their future health and personal care. ACP encourages a person to legally appoint a substitute decision maker (SDM) and to document any specific wishes regarding their future health care in an advance care directive (ACD). Formal documentation of wishes increases the chances that a person's wishes will be known and followed. However, one of the biggest impediments for doctors following the person's wishes is uncertainty surrounding the law, which is complicated and varies between the states and territories of Australia. SDM legislation varies regarding who can be appointed, how they are appointed, the powers that an SDM can be given and the decision-making principles that the SDM needs to follow. In circumstances where an SDM has not been appointed, the hierarchy for determining the default SDM for a person also varies between states. Although many states have legislated ACD forms allowing for documentation of a person's health care wishes, these forms allow for different things to be documented and have different requirements to be valid. The Australian population is mobile, with patients frequently moving between states. The status of ACP documentation created in a state other than the state in which a patient requires treatment also varies, with some states recognising interstate ACDs whereas others do not. This article outlines the legal status of ACDs, within Australian jurisdictions, including the legal validity of interstate ACDs, and argues that uniform laws and documents would assist with awareness and understanding of, and compliance with, ACDs.
Validating administrative records in post-traumatic stress disorder.
Abrams, Thad E; Vaughan-Sarrazin, Mary; Keane, Terence M; Richardson, Kelly
2016-03-01
There is insufficient data on the accuracy of administrative coding data (ACD) for post-traumatic stress disorder (PTSD). Medical records were reviewed for (1) a diagnosis of PTSD; (2) treatment for PTSD. The records were compared against the Veterans Health Administration (VHA) data in order to determine the positive predictive value (PPV) and negative predictive value (NPV) of three commonly used approaches. The PPV and NPV varied according to the ACD approach. Relative to a medical records review, the ACD approach of one or two PTSD coded outpatient encounters had a PPV of 78% and an NPV of 91%; whereas the PPV was 97% and the NPV was 98% for three or more PTSD codes. For pharmacotherapy, the ACD approach with one or two codes for PTSD had a PPV of 33% (NPV = 93%), whereas three or more PTSD coded encounters improved the PPV to 85% (NPV = 100%). When using VHA data, we recommend tailoring the identification strategy according to the research aims. An ACD approach identifying one or more PTSD outpatient encounters should be considered sufficient for a diagnosis of PTSD. Assessments for PTSD associated pharmacotherapy require using an ACD approach that identifies veterans with the presence ≥ 3 outpatient PTSD encounters. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Liang, Peng; Wu, Wenlong; Wei, Jincheng; Yuan, Lulu; Xia, Xue; Huang, Xia
2011-08-01
A bioelectrochemical system (BES) can be operated in both "microbial fuel cell" (MFC) and "microbial electrolysis cell" (MEC) modes, in which power is delivered and invested respectively. To enhance the electric current production, a BES was operated in MFC mode first and a capacitor was used to collect power from the system. Then the charged capacitor discharged electrons to the system itself, switching into MEC mode. This alternate charging and discharging (ACD) mode helped the system produce 22-32% higher average current compared to an intermittent charging (IC) mode, in which the capacitor was first charged from an MFC and then discharged to a resistor, at 21.6 Ω external resistance, 3.3 F capacitance and 300 mV charging voltage. The effects of external resistance, capacitance and charging voltage on average current were studied. The average current reduced as the external resistance and charging voltage increased and was slightly affected by the capacitance. Acquisition of higher average current in the ACD mode was attributed to the shorter discharging time compared to the charging time, as well as a higher anode potential caused by discharging the capacitor. Results from circuit analysis and quantitatively calculation were consistent with the experimental observations.
Zinkevičienė, Auksė; Kainov, Denis; Girkontaitė, Irutė; Lastauskienė, Eglė; Kvedarienė, Violeta; Fu, Yu; Anders, Simon; Velagapudi, Vidya
2016-01-01
Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The severity and duration of this disease are associated with many different factors. Some of these factors may represent markers for monitoring disease activity and the individual response to an intervention. We used a targeted metabolomics approach to find such factors in the serum of individuals with ACD. Metabolomics profiles were examined and compared in the acute phase of the disease and also in the absence of disease activity. Our study identified a significant remission phase of ACD-associated systemic biochemical shifts in 2 metabolic pathways: tryptophan-kynurenine and phenylalanine-tyrosine. Although the responsible mechanisms are unclear, these results suggest that the remission phase of ACD is linked to tryptophan metabolism via kynurenine and phenylalanine-tyrosine pathways. However, further replication studies with a larger number of subjects and their subgroups are necessary to validate our results. These studies may provide a new perspective with which to understand the mechanism of and find potential biomarkers of ACD, as well as a new reference for personalized treatment. © 2016 S. Karger AG, Basel.
The comparison of detection methods of asymptomatic malaria in hypoendemic areas
NASA Astrophysics Data System (ADS)
Siahaan, L.; Panggabean, M.; Panggabean, Y. C.
2018-03-01
Malaria is still a problem that disrupts public health in North Sumatera. Late diagnosis will increase the chances of increased morbidity and mortality due to malaria. The early detection of asymptomatic malaria is one of the best efforts to reduce the transmission of the disease. Early detection is certainly must be done on suspect patients who have no malaria complaints. Passive Case Detection (PCD) methods seem hard to find asymptomatic malaria. This study was conducted to compare ACD (Active Case Detection) and PCD methods in asymptomatic malaria detection in the hypoendemic areas of malaria. ACD method is done by going to the sample based on secondary data. Meanwhile, PCD is done on samples that come to health services. Samples were taken randomly and diagnosis was confirmed by microscopic examination with 3% Giemsa staining, as gold standard of malaria diagnostics. There was a significant difference between ACD and PCD detection methods (p = 0.034), where ACD method was seen superior in detecting malaria patients in all categories, such as: clinical malaria (65.2%), asymptomatic malaria (65.1%) and submicroscopic malaria (58.5%). ACD detection methods are superior in detecting malaria sufferers, especially asymptomatic malaria sufferers.
Kovacevic, Ismar; Bao, Zhirong
2018-01-01
C. elegans cell divisions that produce an apoptotic daughter cell exhibit Daughter Cell Size Asymmetry (DCSA), producing a larger surviving daughter cell and a smaller daughter cell fated to die. Genetic screens for mutants with defects in apoptosis identified several genes that are also required for the ability of these divisions to produce daughter cells that differ in size. One of these genes, ham-1, encodes a putative transcription factor that regulates a subset of the asymmetric cell divisions that produce an apoptotic daughter cell. In a survey of C. elegans divisions, we found that ham-1 mutations affect primarily anterior/posterior divisions that produce a small anterior daughter cell. The affected divisions include those that generate an apoptotic cell as well as those that generate two surviving cells. Our findings suggest that HAM-1 primarily promotes DCSA in a certain class of asymmetric divisions. PMID:29668718
Stationary Size Distributions of Growing Cells with Binary and Multiple Cell Division
NASA Astrophysics Data System (ADS)
Rading, M. M.; Engel, T. A.; Lipowsky, R.; Valleriani, A.
2011-10-01
Populations of unicellular organisms that grow under constant environmental conditions are considered theoretically. The size distribution of these cells is calculated analytically, both for the usual process of binary division, in which one mother cell produces always two daughter cells, and for the more complex process of multiple division, in which one mother cell can produce 2 n daughter cells with n=1,2,3,… . The latter mode of division is inspired by the unicellular algae Chlamydomonas reinhardtii. The uniform response of the whole population to different environmental conditions is encoded in the individual rates of growth and division of the cells. The analytical treatment of the problem is based on size-dependent rules for cell growth and stochastic transition processes for cell division. The comparison between binary and multiple division shows that these different division processes lead to qualitatively different results for the size distribution and the population growth rates.
Contact dermatitis to Vicks VapoRub.
Noiles, Kristin; Pratt, Melanie
2010-01-01
Vicks VapoRub (VVR) is a commonly used inhalant ointment that helps relieve symptoms of upper respiratory tract infections. It contains several plant substances, including turpentine oil, eucalyptus oil, and cedar leaf oil, which can potentially irritate or sensitize the skin, as well as camphor, menthol, nutmeg oil, and thymol. Although many reports describe allergic contact dermatitis (ACD) to the various constituents in VVR ointment, there are no cases of VVR directly causing ACD. We present a case of a patient who developed an ACD secondary to application of her VVR.
Nakakura, Shunsuke; Mori, Etsuko; Nagatomi, Nozomi; Tabuchi, Hitoshi; Kiuchi, Yoshiaki
2012-07-01
To evaluate the congruity of anterior chamber depth (ACD) measurements using 4 devices. Saneikai Tsukazaki Hospital, Himeji City, Japan. Comparative case series. In 1 eye of 42 healthy participants, the ACD was measured by 3-dimensional corneal and anterior segment optical coherence tomography (CAS-OCT), partial coherence interferometry (PCI), Scheimpflug imaging, and ultrasound biomicroscopy (UBM). The differences between the measurements were evaluated by 2-way analysis of variance and post hoc analysis. Agreement between the measurements was evaluated using Bland-Altman analysis. To evaluate the true ACD using PCI, the automatically calculated ACD minus the central corneal thickness measured by CAS-OCT was defined as PCI true. Two ACD measurements were also taken with CAS-OCT. The mean ACD was 3.72 mm ± 0.23 (SD) (PCI), 3.18 ± 0.23 mm (PCI true), 3.24 ± 0.25 mm (Scheimpflug), 3.03 ± 0.25 mm (UBM), 3.14 ± 0.24 mm (CAS-OCT auto), and 3.12 ± 0.24 mm (CAS-OCT manual). A significant difference was observed between PCI biometry, Scheimpflug imaging, and UBM measurements and the other methods. Post hoc analysis showed no significant differences between PCI true and CAS-OCT auto or between CAS-OCT auto and CAS-OCT manual. Strong correlations were observed between all measurements; however, Bland-Altman analysis showed good agreement only between PCI true and Scheimpflug imaging and between CAS-OCT auto and CAS OCT manual. The ACD measurements obtained from PCI biometry, Scheimpflug imaging, CAS-OCT, and UBM were significantly different and not interchangeable except for PCI true and CAS-OCT auto and CAS-OCT auto and CAS-OCT manual. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Anterior surgical management of single-level cervical disc disease: a cost-effectiveness analysis.
Lewis, Daniel J; Attiah, Mark A; Malhotra, Neil R; Burnett, Mark G; Stein, Sherman C
2014-12-01
Cost-effectiveness analysis with decision analysis and meta-analysis. To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1-level cervical disc disease. There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment. A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches. At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years. The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive conclusions about degenerative changes after ACD and adjacent-level disease after CDR await longer follow-up. 4.
Haidar, Ali N; Zasada, Stefan J; Coveney, Peter V; Abdallah, Ali E; Beckles, Bruce; Jones, Mike A S
2011-06-06
We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username-password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale.
Hair-care practices in African American women: potential for allergic contact dermatitis.
Stallings, Alicia; Sood, Apra
2016-12-01
Allergic contact dermatitis (ACD) is a delayed hypersensitivity reaction that occurs when the skin is re-exposed to a substance to which it was previously sensitized. One significant source of exposure to sensitizing chemicals is through personal grooming and beauty products. While the role of cosmetics and hair-care products in the development of ACD is well-documented, there has been very little literature that specifically addresses the role of hair-care practices of patients with tightly curled hair, such as in patients of African descent, in the development of ACD in this population. This review provides an integrated summary of the hair-care practices of female African American patients and the potential for exposure to sensitizing agents at each stage. This review will also discuss the challenges faced in recognizing and assessing ACD in these patients. ©2016 Frontline Medical Communications.
Haidar, Ali N.; Zasada, Stefan J.; Coveney, Peter V.; Abdallah, Ali E.; Beckles, Bruce; Jones, Mike A. S.
2011-01-01
We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username–password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale. PMID:22670214
Six children with allergic contact dermatitis to methylisothiazolinone in wet wipes (baby wipes).
Chang, Mary Wu; Nakrani, Radhika
2014-02-01
Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a combination preservative used in personal care and household products and is a common cause of allergic contact dermatitis (ACD). Recently, MI alone, without MCI, has been increasingly used in consumer products in attempts to minimize allergic reactions. Wet wipes are extensively tested and traditionally believed to be innocuous. MI in wet wipes ("baby wipes") has not been previously reported to cause ACD in children in the United States. Only 1 previous report of ACD in a child in Belgium has been recently reported. We report 6 children with chronic, perianal/buttock, and facial eczematous dermatitis, refractory to multiple topical and oral antibiotics and corticosteroids. All tested positive to MCI/MI on patch testing. None wore diapers. All patients had been using wet wipes containing MI (without MCI) to affected areas. Discontinuation of wipes resulted in rapid and complete resolution. This is the first report of pediatric ACD to MI in wet wipes in the United States, and the largest series to date. ACD to MI in wet wipes is frequently misdiagnosed as eczema, impetigo, or psoriasis. Wet wipes are increasingly marketed in personal care products for all ages, and MI exposure and sensitization will likely increase. Dermatitis of the perianal, buttock, facial, and hand areas with a history of wet wipe use should raise suspicion of ACD to MI and prompt appropriate patch testing. Rapid resolution occurs after the allergen exposure is eliminated. All isothiozolinones should be avoided in personal care and household products for these patients.
Approach to Anemia in Hospitalized Patients with Infectious Diseases; Is it Appropriate?
Entezari-Maleki, Taher; Khalili, Hossein; Karimzadeh, Iman; Jafari, Sirous
2015-01-01
Anemia of chronic diseases (ACD) is a common problem in patients with infectious diseases and can influence the quality of life and patients' survival. Despite the clinical importance of ACD, data are still lacking regarding this problem in the infectious diseases. This study aimed to evaluate the prevalence, related factors, outcome and approaches to anemia in the infectious diseases ward. This retrospective study was performed to review the medical records of patients admitted to the infectious diseases department of Imam Khomeini hospital during a two-year period between 2009 and 2011. A standard protocol was developed to evaluate anemia. Patients' demographic data approaches to manage anemia and routine laboratory tests were recorded and compared with the protocol. Totally, 1,120 medical records were reviewed. ACD was recognized in 705 patients (63%). Only 5.1% of diagnostic and 8.7% of treatment approaches was based on the protocol. The majority of patients (89.4%) were received inappropriate treatment regarding. Mortality rate of patients with ACD was 3.4%. Moreover, a significant correlation between anemia and mortality was detected (r = 0.131; p = 0.026). A statistically significant correlation was also identified between patients' Hgb and ESR, CRP, reasons of admission, number of medications, and underlying diseases. In conclusion, results of this study suggested that ACD is a common problem in infectious diseases patients and significantly associated with patients' mortality. Moreover, the majority of studied patients were not received an appropriate diagnostic and treatment approach which arises more concerns regarding the management of ACD in infectious diseases setting.
Translation and validation of the Cardiac Depression Scale to Arabic.
Papasavvas, T; Al-Amin, H; Ghabrash, H F; Micklewright, D
2016-08-01
The Cardiac Depression Scale (CDS) has been designed to measure depressive symptoms in patients with heart disease. There is no Arabic version of the CDS. We translated and validated the CDS in an Arabic sample of patients with heart disease. Forward and back translation of the CDS was followed by assessment of cultural relevance and content validity. The Arabic version of the CDS (A-CDS) and the Arabic version of the Hospital Anxiety and Depression Scale (A-HADS) were then administered to 260 Arab in-patients with heart disease from 18 Arabic countries. Construct validity was assessed using exploratory factor analysis with polychoric correlations. Internal consistency was assessed using ordinal reliability alpha and item-to-factor polychoric correlations. Concurrent validity was assessed using Pearson's correlation coefficient between the A-CDS and the depression subscale of the A-HADS (A-HADS-D). Cultural relevance and content validity of the A-CDS were satisfactory. Exploratory factor analysis revealed three robust factors, without cross-loadings, that formed a single dimension. Internal consistency was high (ordinal reliability alpha for the total scale and the three factors were .94, .91, .86, and .87, respectively; item-to-factor correlations ranged from .77 to .91). Concurrent validity was high (r=.72). The A-CDS demonstrated a closer to normal distribution of scores than the A-HADS-D. Sensitivity and specificity of the A-CDS were not objectively assessed. The A-CDS appears to be a valid and reliable instrument to measure depressive symptoms in a representative sample of Arab in-patients with heart disease. Copyright © 2016 Elsevier B.V. All rights reserved.
Ocular biometric measurements in cataract surgery candidates in Portugal.
Ferreira, Tiago B; Hoffer, Kenneth J; Ribeiro, Filomena; Ribeiro, Paulo; O'Neill, João G
2017-01-01
Describe the ocular biometric parameters and their associations in a population of cataract surgery candidates. A cross-sectional study of 13,012 eyes of 6,506 patients was performed. Biometric parameters of the eyes were measured by optical low-coherence reflectometry. The axial length (AL), mean keratometry (K) and astigmatism, anterior chamber depth (ACD) (epithelium to lens), lens thickness (LT), and Corneal Diameter (CD) were evaluated. The mean age was 69 ± 10 years (44-99 years). Mean AL, Km, and ACD were 23.87 ± 1.55 mm (19.8-31.92 mm), 43.91 ± 1.71 D (40.61-51.14 D), and 3.25 ± 0.44 mm (2.04-5.28 mm), respectively. The mean LT was 4.32 ± 0.49 mm (2.73-5.77 mm) and the mean CD was 12.02 ± 0.46 mm (10.50-14.15 mm). The mean corneal astigmatism was 1.08 ± 0.84 D (0.00-7.58 D) and 43.5% of eyes had astigmatism ≥ 1.00 D. Male patients had longer AL and ACDs (p < .001) and flatter corneas (p < .001). In regression models considering age, gender, Km, ACD, LT, and CD, a longer AL was associated with being male and having higher ACD, LT and CD. These data represent normative biometric values for the Portuguese population. The greatest predictor of ocular biometrics was gender. There was no significant correlation between age and AL, ACD, or Km. These results may be relevant in the evaluation of refractive error and in the calculation of intraocular lens power.
Kim, Jin-Soo; Choi, Jung Yeol; Kwon, Ji-Won; Wee, Won Ryang; Han, Young Keun
2018-01-01
AIM To investigate the effects and safety of neodymium: yttrium-aluminium-garnet (Nd:YAG) laser posterior capsulotomy with vitreous strand cutting METHODS A total of 40 eyes of 37 patients with symptomatic posterior capsular opacity (PCO) were included in this prospective randomized study and were randomly subjected to either cruciate pattern or round pattern Nd:YAG posterior capsulotomy with vitreous strand cutting (modified round pattern). The best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive error, endothelial cell count (ECC), anterior segment parameters, including anterior chamber depth (ACD) and anterior chamber angle (ACA) were measured before and 1mo after the laser posterior capsulotomy. RESULTS In both groups, the BCVA improved significantly (P<0.001 for the modified round pattern group, P=0.001 for the cruciate pattern group); the IOP and ECC did not significantly change. The ACD significantly decreased (P<0.001 for both) and the ACA significantly increased (P=0.001 for the modified round pattern group and P=0.034 for the cruciate group). The extent of changes in these parameters was not significantly different between the groups. CONCLUSION Modified round pattern Nd:YAG laser posterior capsulotomy is an effective and safe method for the treatment of PCO. This method significantly changes the ACD and ACA, but the change in refraction is not significant. Modified round pattern Nd:YAG laser posterior capsulotomy can be considered a good alternative procedure in patients with symptomatic PCO. PMID:29487812
Kim, Jin-Soo; Choi, Jung Yeol; Kwon, Ji-Won; Wee, Won Ryang; Han, Young Keun
2018-01-01
To investigate the effects and safety of neodymium: yttrium-aluminium-garnet (Nd:YAG) laser posterior capsulotomy with vitreous strand cutting. A total of 40 eyes of 37 patients with symptomatic posterior capsular opacity (PCO) were included in this prospective randomized study and were randomly subjected to either cruciate pattern or round pattern Nd:YAG posterior capsulotomy with vitreous strand cutting (modified round pattern). The best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive error, endothelial cell count (ECC), anterior segment parameters, including anterior chamber depth (ACD) and anterior chamber angle (ACA) were measured before and 1mo after the laser posterior capsulotomy. In both groups, the BCVA improved significantly ( P <0.001 for the modified round pattern group, P =0.001 for the cruciate pattern group); the IOP and ECC did not significantly change. The ACD significantly decreased ( P <0.001 for both) and the ACA significantly increased ( P =0.001 for the modified round pattern group and P =0.034 for the cruciate group). The extent of changes in these parameters was not significantly different between the groups. Modified round pattern Nd:YAG laser posterior capsulotomy is an effective and safe method for the treatment of PCO. This method significantly changes the ACD and ACA, but the change in refraction is not significant. Modified round pattern Nd:YAG laser posterior capsulotomy can be considered a good alternative procedure in patients with symptomatic PCO.
Spiewak, Radoslaw; Moed, Heleen; von Blomberg, Brigitta Mary E; Bruynzeel, Derk P; Scheper, Rik J; Gibbs, Susan; Rustemeyer, Thomas
2007-02-01
To date, no in vitro test is suitable for routine diagnosis of contact allergy. The aim of our study was to establish improved in vitro test protocol for the detection of antigen-specific responses of lymphocytes from patients with allergic contact dermatitis to nickel (Ni-ACD). Blood leucocytes from 14 Ni-ACD patients and 14 controls were cultured in the presence of 'cytokine cocktails' skewing lymphocytes towards 'type 1' [interferon-gamma (IFN-gamma)-secreting] or 'type 2' [interleukin (IL)-5 and IL-13-secreting] phenotypes. The cocktails consisted of IL-7 and, respectively, either IL-12 or IL-4. Cell responses to nickel were measured with enzyme-linked immunospot assay (ELISpot), enzyme-linked immunosorbent assay (ELISA), and lymphocyte proliferation test (LPT). Significant differences between patients with Ni-ACD and controls were found for the 'type 2' cytokines IL-13 and IL-5, with further increase of allergen-specific responses occurring when cultures were supplemented with IL-7 and IL-4. No significant differences were found for IFN-gamma. The best correlate to clinical diagnosis was LPT with 'type 2' skewing (r= 0.739, P < 0.001), followed by IL-13 ELISpot with 'type 2' skewing (r= 0.654, P < 0.001). The non-radioactive method that correlated best with LPT was IL-2 ELISpot (r= 0.809, P < 0.001). Overall, we conclude that combining ELISpot assay with proposed modifications of culture conditions improves detection of specific lymphocyte responses in contact allergy to nickel.
Wang, Michael F Z; Hunter, Miranda V; Wang, Gang; McFaul, Christopher; Yip, Christopher M; Fernandez-Gonzalez, Rodrigo
2017-04-01
Embryos extend their anterior-posterior (AP) axis in a conserved process known as axis elongation. Drosophila axis elongation occurs in an epithelial monolayer, the germband, and is driven by cell intercalation, cell shape changes, and oriented cell divisions at the posterior germband. Anterior germband cells also divide during axis elongation. We developed image analysis and pattern-recognition methods to track dividing cells from confocal microscopy movies in a generally applicable approach. Mesectoderm cells, forming the ventral midline, divided parallel to the AP axis, while lateral cells displayed a uniform distribution of division orientations. Mesectoderm cells did not intercalate and sustained increased AP strain before cell division. After division, mesectoderm cell density increased along the AP axis, thus relieving strain. We used laser ablation to isolate mesectoderm cells from the influence of other tissues. Uncoupling the mesectoderm from intercalating cells did not affect cell division orientation. Conversely, separating the mesectoderm from the anterior and posterior poles of the embryo resulted in uniformly oriented divisions. Our data suggest that mesectoderm cells align their division angle to reduce strain caused by mechanical forces along the AP axis of the embryo. © 2017. Published by The Company of Biologists Ltd.
Concerted control of Escherichia coli cell division
Osella, Matteo; Nugent, Eileen; Cosentino Lagomarsino, Marco
2014-01-01
The coordination of cell growth and division is a long-standing problem in biology. Focusing on Escherichia coli in steady growth, we quantify cell division control using a stochastic model, by inferring the division rate as a function of the observable parameters from large empirical datasets of dividing cells. We find that (i) cells have mechanisms to control their size, (ii) size control is effected by changes in the doubling time, rather than in the single-cell elongation rate, (iii) the division rate increases steeply with cell size for small cells, and saturates for larger cells. Importantly, (iv) the current size is not the only variable controlling cell division, but the time spent in the cell cycle appears to play a role, and (v) common tests of cell size control may fail when such concerted control is in place. Our analysis illustrates the mechanisms of cell division control in E. coli. The phenomenological framework presented is sufficiently general to be widely applicable and opens the way for rigorous tests of molecular cell-cycle models. PMID:24550446
Occupational dermatitis in health care workers evaluated for suspected allergic contact dermatitis.
Kadivar, Salmon; Belsito, Donald V
2015-01-01
Contact dermatitides occur commonly among health care workers (HCWs). To contrast the atopic status and incidence, location, and final diagnosis of skin diseases afflicting HCWs versus non-HCWs (NHCWs) evaluated for suspicion of allergic contact dermatitis (ACD); and among the population diagnosed with ACD, to compare the incidence and occupational relatedness of allergens found in HCWs with the rates observed in NHCWs. Between July 1, 1994, and May 30, 2014, 2611 patients underwent patch testing by the senior author. Of these, 165 were classified as HCWs based on their primary occupation. Statistical analysis was done using a χ test. Health care workers were more likely than NHCWs to be women and to have hand dermatitis. Women, but not men, HCWs suffered more irritant contact dermatitis. Health care workers had significantly more work-related ACD, especially to formaldehyde, quaternium-15, 2-bromo-2-nitropropane-1,3-diol, cocamide diethanolamine (DEA), thiuram mix, carba mix, thimerosal, benzalkonium chloride, glutaraldehyde, and bacitracin. Only patients suspected of having ACD were tested. Our population was geographically limited to metropolitan Kansas City, MO and metropolitan New York, NY. Health care workers suffer more from occupational ACD, especially of the hands, than do NHCWs, including to allergens not present on available standard allergen series.
On-Orbit ACDS Performance of the Landsat 7 Spacecraft
NASA Technical Reports Server (NTRS)
Sabelhaus, Phillip; Bolek, Joseph; Scott, Steve; Holmes, Eric; O'Donnell, James R., Jr.; Storey, James
2001-01-01
Landsat 7 is part of NASA's Earth Science Enterprise (ESE). The ESE is committed to developing an understanding of the total Earth system, the effects of natural and human-induced changes on the global environment, and how natural processes affect humans and how humans affect them. The Landsat 7 satellite consists of the spacecraft bus which was provided under a NASA contract with Lockheed Martin Missiles and Space in Philadelphia, PA, and the Enhanced Thematic Mapper-Plus (ETM+) instrument, procured under a NASA contract with Raytheon Santa Barbara Remote Sensing, in Santa Barbara, CA. The Landsat 7 Attitude Control and Determination System (ACDS) provides many essential functions for the operation of the spacecraft bus and for ETM+. The ACDS maintains the required attitude and orbit at the degree of accuracy necessary for power generation, command and telemetry, thermal balance, image acquisition, Gimbaled X-Band Antenna (GXA) pointing and data for image post-processing. Descriptions of the Landsat 7 mission and the ACDS modes and requirements are presented. A brief summary of significant events of the on-orbit initialization and validation period are provided. Finally, the Landsat 7 product generation system is described and the impact that the ACDS performance has on the ground based image processing system is explored.
Zaragoza-Ninet, V; Blasco Encinas, R; Vilata-Corell, J J; Pérez-Ferriols, A; Sierra-Talamantes, C; Esteve-Martínez, A; de la Cuadra-Oyanguren, J
2016-05-01
The incidence of allergic contact dermatitis (ACD) to cosmetics in the general population is rising with the increasing use of cosmetic products and their proliferation and diversification. The aims of this study were to determine the prevalence of ACD to cosmetics in our setting, analyze changes over time, describe the clinical and epidemiological features of this allergic reaction, and identify the allergens and cosmetics involved. We performed a prospective study at the skin allergy unit in Hospital General Universitario de Valencia in Spain between 2005 and 2013 and compared our findings with data collected retrospectively for the period 1996 to 2004. The 5419 patients who underwent patch testing during these 2 periods were included in the study. The mean prevalence of ACD to cosmetics increased from 9.8% in the first period (1996-2004) to 13.9% in the second period (2005-2013). A significant correlation was found between ACD to cosmetics and female sex but not atopy. Kathon CG (blend of methylchloroisothiazolinone and methylisothiazolinone), fragrances, and paraphenylenediamine were the most common causes of ACD to cosmetics during both study periods, and acrylates and sunscreens were identified as emerging allergens during the second period. Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.
Conforte, Valeria P; Echeverria, Mariela; Sánchez, Cintia; Ugalde, Rodolfo A; Menéndez, Ana B; Lepek, Viviana C
2010-08-01
Ethylene inhibits the establishment of symbiosis between rhizobia and legumes. Several rhizobia species express the enzyme ACC deaminase, which degrades the ethylene precursor 1-cyclopropane-1-carboxilate (ACC), leading to reductions in the amount of ethylene evolved by the plant. M. loti has a gene encoding ACC deaminase, but this gene is under the activity of the NifA-RpoN-dependent promoter; thus, it is only expressed inside the nodule. The M. loti structural gene ACC deaminase (acdS) was integrated into the M. loti chromosome under a constitutive promoter activity. The resulting strain induced the formation of a higher number of nodules and was more competitive than the wild-type strain on Lotus japonicus and L. tenuis. These results suggest that the introduction of the ACC deaminase activity within M. loti in a constitutive way could be a novel strategy to increase nodulation competitiveness of the bacteria, which could be useful for the forage inoculants industry.
Huang, Xinxin; Tian, E; Xu, Yanhua; Zhang, Hong
2009-09-15
Stem cells undergo symmetric and asymmetric division to maintain the dynamic equilibrium of the stem cell pool and also to generate a variety of differentiated cells. The homeostatic mechanism controlling the choice between self-renewal and differentiation of stem cells is poorly understood. We show here that ceh-16, encoding the C. elegans ortholog of the transcription factor Engrailed, controls symmetric and asymmetric division of stem cell-like seam cells. Loss of function of ceh-16 causes certain seam cells, which normally undergo symmetric self-renewal expansion division with both daughters adopting the seam cell fate, to divide asymmetrically with only one daughter retaining the seam cell fate. The human engrailed homolog En2 functionally substitutes the role of ceh-16 in promoting self-renewal expansion division of seam cells. Loss of function of apr-1, encoding the C. elegans homolog of the Wnt signaling component APC, results in transformation of self-renewal maintenance seam cell division to self-renewal expansion division, leading to seam cell hyperplasia. The apr-1 mutation suppresses the seam cell division defect in ceh-16 mutants. Our study reveals that ceh-16 interacts with the Wnt signaling pathway to control the choice between self-renewal expansion and maintenance division and also demonstrates an evolutionarily conserved function of engrailed in promoting cell proliferation.
Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U
2015-03-14
There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not significantly influence cell counts or GF concentrations in equine PRP. However, ACD-B was apparently the worst anticoagulant evaluated. It is necessary to perform additional research to determine the effect of anticoagulants on the kinetics of GF elution from P-PRG.
Quantitative regulation of B cell division destiny by signal strength.
Turner, Marian L; Hawkins, Edwin D; Hodgkin, Philip D
2008-07-01
Differentiation to Ab secreting and isotype-switched effector cells is tightly linked to cell division and therefore the degree of proliferation strongly influences the nature of the immune response. The maximum number of divisions reached, termed the population division destiny, is stochastically distributed in the population and is an important parameter in the quantitative outcome of lymphocyte responses. In this study, we further assessed the variables that regulate B cell division destiny in vitro in response to T cell- and TLR-dependent stimuli. Both the concentration and duration of stimulation were able to regulate the average maximum number of divisions undergone for each stimulus. Notably, a maximum division destiny was reached during provision of repeated saturating stimulation, revealing that an intrinsic limit to proliferation exists even under these conditions. This limit was linked directly to division number rather than time of exposure to stimulation and operated independently of the survival regulation of the cells. These results demonstrate that a B cell population's division destiny is regulable by the stimulatory conditions up to an inherent maximum value. Division destiny is a crucial parameter in regulating the extent of B cell responses and thereby also the nature of the immune response mounted.
Yap, Kevin Yi-Lwern; Ho, Yasmin Xiu Xiu; Chui, Wai Keung; Chan, Alexandre
2010-11-01
Concomitant use of anticancer drugs (ACDs) and antidepressants (ADs) in the treatment of depression in patients with cancer may result in potentially harmful drug-drug interactions (DDIs). It is crucial that clinicians make timely, accurate, safe and effective decisions regarding drug therapies in patients. The ubiquitous nature of the internet or "cloud" has enabled easy dissemination of DDI information, but there is currently no database dedicated to allow searching of ACD interactions by chemotherapy regimens. We describe the implementation of an AD interaction module to a previously published oncology-specific DDI database for clinicians which focuses on ACDs, single-agent and multiple-agent chemotherapy regimens. Drug- and DDI-related information were collated from drug information handbooks, databases, package inserts, and published literature from PubMed, Scopus and Science Direct. Web documents were constructed using Adobe software and programming scripts, and mounted on a domain served from the internet cloud. OncoRx is an oncology-specific DDI database whose structure is designed around all the major classes of ACDs and their frequently prescribed chemotherapy regimens. There are 117 ACDs and 256 regimens in OncoRx, and it can detect over 1 500 interactions with 21 ADs. Clinicians are provided with the pharmacokinetic parameters of the drugs, information on the regimens and details of the detected DDIs during an interaction search. OncoRx is the first database of its kind which allows detection of ACD and chemotherapy regimen interactions with ADs. This tool will assist clinicians in improving clinical response and reducing adverse effects based on the therapeutic and toxicity profiles of the drugs.
Inada, Noriko; Shoji, Jun; Kato, Hiroshi; Kiely, Surayah; Mulyanto; Sawa, Mitsuru
2009-12-01
The determination of total IgE in tears is useful as a diagnostic tool in allergic conjunctivitis disease (ACD). We evaluated the efficacy of this diagnostic tool for ACD, which is a clinically applicable novel immunochromagraphic method to determine total IgE in tears. The subjects comprised 4 groups: 15 patients with vernal keratoconjunctivitis (VKC group), 8 patients with atopic keratoconjunctivitis (AKC group), 18 patients with allergic conjunctivitis (AC group), and 7 normal healthy volunteers as a control (control group). Tears were sampled using filter paper, and the total IgE in tears was determined by immunochromatography assay. Semiquantitative determination was carried out by examining the intensity of the colored line using an immunochromatoreader (IgE index). The relationship between IgE indices in tears and total IgE levels in serum or between IgE indices and the clinical scores of ACD was examined. The positive ratio obtained by this novel application of the immunochromatography assay was 38 of the 41 in the patients with ACD and none in the 7 controls. IgE indices for the VKC group, AKC group and AC group were 27.5 +/- 15.6, 19.8 +/- 15.8, and 4.0 +/- 3.1 (mean +/- SD), respectively. IgE indices in tears showed significant correlation with both total IgE levels in serum (P < 0.001, r = 0.76) and clinical scores of ACD (P < 0.001, r = 0.57). The novel application of the immunochromatography assay to assess the total IgE in tears is a useful clinical tool to investigate ACD.
Ocular biometric measurements in cataract surgery candidates in Portugal
Hoffer, Kenneth J.; Ribeiro, Filomena; Ribeiro, Paulo; O’Neill, João G.
2017-01-01
Objective Describe the ocular biometric parameters and their associations in a population of cataract surgery candidates. Methods A cross-sectional study of 13,012 eyes of 6,506 patients was performed. Biometric parameters of the eyes were measured by optical low-coherence reflectometry. The axial length (AL), mean keratometry (K) and astigmatism, anterior chamber depth (ACD) (epithelium to lens), lens thickness (LT), and Corneal Diameter (CD) were evaluated. Results The mean age was 69 ± 10 years (44–99 years). Mean AL, Km, and ACD were 23.87 ± 1.55 mm (19.8–31.92 mm), 43.91 ± 1.71 D (40.61–51.14 D), and 3.25 ± 0.44 mm (2.04–5.28 mm), respectively. The mean LT was 4.32 ± 0.49 mm (2.73–5.77 mm) and the mean CD was 12.02 ± 0.46 mm (10.50–14.15 mm). The mean corneal astigmatism was 1.08 ± 0.84 D (0.00–7.58 D) and 43.5% of eyes had astigmatism ≥ 1.00 D. Male patients had longer AL and ACDs (p < .001) and flatter corneas (p < .001). In regression models considering age, gender, Km, ACD, LT, and CD, a longer AL was associated with being male and having higher ACD, LT and CD. Conclusions These data represent normative biometric values for the Portuguese population. The greatest predictor of ocular biometrics was gender. There was no significant correlation between age and AL, ACD, or Km. These results may be relevant in the evaluation of refractive error and in the calculation of intraocular lens power. PMID:28982150
A method for profiling biometric changes during disaccommodation.
Alderson, Alison; Davies, Leon N; Mallen, Edward A H; Sheppard, Amy L
2012-05-01
To demonstrate the application of low-coherence reflectometry to the study of biometric changes during disaccommodation responses in human eyes after cessation of a near task and to evaluate the effect of contact lenses on low-coherence reflectometry biometric measurements. Ocular biometric parameters of crystalline lens thickness (LT) and anterior chamber depth (ACD) were measured with the LenStar device during and immediately after a 5 D accommodative task in 10 participants. In a separate trial, accommodation responses were recorded with a Shin-Nippon WAM-5500 optometer in a subset of two participants. Biometric data were interleaved to form a profile of post-task anterior segment changes. In a further experiment, the effect of soft contact lenses on LenStar measurements was evaluated in 15 participants. In 10 adult participants, increased LT and reduced ACD was seen during the 5 D task. Post-task, during fixation of a 0 D target, a profile of the change in LT and ACD against time was observed. In the two participants with accommodation data (one a sufferer of nearwork-induced transient myopia and other a non-sufferer), the post-task changes in refraction compared favorably with the interleaved LenStar biometry data. The insertion of soft contact lenses did not have a significant effect on LenStar measures of ACD or LT (mean change: -0.007 mm, p = 0.265 and + 0.001 mm, p = 0.875, respectively). With the addition of a relatively simple stimulus modification, the LenStar instrument can be used to produce a profile of post-task changes in LT and ACD. The spatial and temporal resolution of the system is sufficient for the investigation of nearwork-induced transient myopia from a biometric viewpoint. LenStar measurements of ACD and LT remain valid after the fitting of soft contact lenses.
Griffith, Megan E.; Mayer, Ulrike; Capron, Arnaud; Ngo, Quy A.; Surendrarao, Anandkumar; McClinton, Regina; Jürgens, Gerd; Sundaresan, Venkatesan
2007-01-01
Embryogenesis in Arabidopsis thaliana is marked by a predictable sequence of oriented cell divisions, which precede cell fate determination. We show that mutation of the TORMOZ (TOZ) gene yields embryos with aberrant cell division planes and arrested embryos that appear not to have established normal patterning. The defects in toz mutants differ from previously described mutations that affect embryonic cell division patterns. Longitudinal division planes of the proembryo are frequently replaced by transverse divisions and less frequently by oblique divisions, while divisions of the suspensor cells, which divide only transversely, appear generally unaffected. Expression patterns of selected embryo patterning genes are altered in the mutant embryos, implying that the positional cues required for their proper expression are perturbed by the misoriented divisions. The TOZ gene encodes a nucleolar protein containing WD repeats. Putative TOZ orthologs exist in other eukaryotes including Saccharomyces cerevisiae, where the protein is predicted to function in 18S rRNA biogenesis. We find that disruption of the Sp TOZ gene results in cell division defects in Schizosaccharomyces pombe. Previous studies in yeast and animal cells have identified nucleolar proteins that regulate the exit from M phase and cytokinesis, including factors involved in pre-rRNA processing. Our study suggests that in plant cells, nucleolar functions might interact with the processes of regulated cell divisions and influence the selection of longitudinal division planes during embryogenesis. PMID:17616738
Polarized Cell Division of Chlamydia trachomatis
Abdelrahman, Yasser; Ouellette, Scot P.; Belland, Robert J.; Cox, John V.
2016-01-01
Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the leading bacterial cause of sexually transmitted infections and trachoma, lacks FtsZ, it has been assumed to divide by binary fission. We show here that Chlamydia divides by a polarized cell division process similar to the budding process of a subset of the Planctomycetes that also lack FtsZ. Prior to cell division, the major outer-membrane protein of Chlamydia is restricted to one pole of the cell, and the nascent daughter cell emerges from this pole by an asymmetric expansion of the membrane. Components of the chlamydial cell division machinery accumulate at the site of polar growth prior to the initiation of asymmetric membrane expansion and inhibitors that disrupt the polarity of C. trachomatis prevent cell division. The polarized cell division of C. trachomatis is the result of the unipolar growth and FtsZ-independent fission of this coccoid organism. This mechanism of cell division has not been documented in other human bacterial pathogens suggesting the potential for developing Chlamydia-specific therapeutic treatments. PMID:27505160
[The study of anticoagulants selection in platelet-rich plasma preparation].
Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma
2015-07-01
To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.
NASA Technical Reports Server (NTRS)
Vasilenko, A.; McDaniel, J. K.; Conger, B. V.
2000-01-01
Somatic embryos initiate and develop directly from single mesophyll cells in in vitro-cultured leaf segments of orchardgrass (Dactylis glomerata L.). Embryogenic cells establish themselves in the predivision stage by formation of thicker cell walls and dense cytoplasm. Electron microscopy observations for embryos ranging from the pre-cell-division stage to 20-cell proembryos confirm previous light microscopy studies showing a single cell origin. They also confirm that the first division is predominantly periclinal and that this division plane is important in establishing embryo polarity and in determining the embryo axis. If the first division is anticlinal or if divisions are in random planes after the first division, divisions may not continue to produce an embryo. This result may produce an embryogenic cell mass, callus formation, or no structure at all. Grant numbers: NAGW-3141, NAG10-0221.
Mechanical stretch triggers rapid epithelial cell division through Piezo1.
Gudipaty, S A; Lindblom, J; Loftus, P D; Redd, M J; Edes, K; Davey, C F; Krishnegowda, V; Rosenblatt, J
2017-03-02
Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state. Here we show that mammalian epithelial cell division occurs in regions of low cell density where cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the Piezo1 channel. To stimulate cell division, stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at the steady state, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated, as it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions in which cells divide, Piezo1 localizes to the plasma membrane and cytoplasm, whereas in dense regions in which cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions.
Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal
Ito, Kyoko; Ito, Keisuke
2016-01-01
Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603
Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal.
Ito, Kyoko; Ito, Keisuke
2016-10-06
Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical.
Sedaghat, Mohammad Reza; Azimi, Ali; Arasteh, Peyman; Tehranian, Naghmeh; Bamdad, Shahram
2016-10-01
Basic anatomical parameters in ophthalmology are variable in different countries according to ethnic groups, genetics and some environmental factors. The aim of this study was to determine the relationship between axial length (AL), anterior chamber depth (ACD) and intraocular lens power (IOL) in a referral center from eastern Iran among patients who had cataract surgery, in comparison to studies from other regions of the world. In a cross-sectional retrospective study from 2011 to 2013, the records of 698 cataract patients referring to Khatam Al Anbia general hospital in Mashhad, Iran were evaluated. We divided patients, based on their AL and ACD, into three separate groups and compared their results. The SPSS software was used for data analysis. The Chi-Square test and the Independent-samples t-test were used to compare qualitative and quantitative data between two groups, respectively. The Kendall and the Pearson product-moment correlation tests were used to assess the relationship between AL and ACD. The linear Regression model was used to obtain a mathematical model to estimate ACD, using AL, age and sex. Among individuals who had normal AL (between 22-24.5mm), there was a positive correlation between AL and ACD (p<0.001, r=0.17), however, among individuals with short (AL<22mm) or long sightedness (AL>24.5mm), no significant correlation was detected. We also found that older people have shorter AL (p=0.001 and r=-0.287). Men have an average longer AL (23.7±2.4mm vs. 22.9±2.1mm; p<0.001) and deeper ACD compared to women (2.93±0.45mm vs. 2.82±0.42mm, p=0.002). Our findings were mostly similar to previous literature from other regions of the world and although some anatomical variations may exist regarding ophthalmic anatomy, factors like race and geographical area have little effect on the relationship between ACD, AL and IOL power calculation, furthermore our results support the use of third and fourth generation formulas for IOL power calculation.
Raposo, Inês; Lobo, Inês; Amaro, Cristina; Lobo, Maria de Lurdes; Melo, Helena; Parente, Joana; Pereira, Teresa; Rocha, Joana; Cunha, Ana P; Baptista, Armando; Serrano, Pedro; Correia, Teresa; Travassos, Ana R; Dias, Margarida; Pereira, Fátima; Gonçalo, Margarida
2017-12-01
The increasing use of long-lasting nail aesthetic products has led to a growing number of cases of allergic contact dermatitis (ACD) caused by (meth)acrylates in recent years. To provide information on ACD caused by (meth)acrylates related to nail cosmetic products. We retrospectively reviewed files of patients with ACD caused by (meth)acrylates related to nail cosmetic products, who were patch tested between January 2011 and December 2015 in 13 departments of dermatology in Portugal. Two-hundred and thirty cases of ACD caused by (meth)acrylates (55 technicians, 56 consumers, and 119 with mixed exposure) had been documented, mostly as chronic hand eczema (93%). The most common sensitizers were: 2-hydroxyethyl methacrylate (HEMA), which was positive in 90% of the tested patients, 2-hydroxypropyl methacrylate (HPMA), which was positive in 64.1%, and ethyleneglycol dimethacrylate, which was positive in 54.5%. HEMA and HPMA were the most frequent positive allergens. HEMA, which identified 90% of cases, can be considered to be a good screening allergen. The high number of cases of ACD caused by (meth)acrylates in nail cosmetic products certainly warrants better preventive measures at the occupational level, and specific regulation in the field of consumer safety. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Investigation of veritcal graded channel doping in nanoscale fully-depleted SOI-MOSFET
NASA Astrophysics Data System (ADS)
Ramezani, Zeinab; Orouji, Ali A.
2016-10-01
For achieving reliable transistor, we investigate an amended channel doping (ACD) engineering which improves the electrical and thermal performances of fully-depleted silicon-on-insulator (SOI) MOSFET. We have called the proposed structure with the amended channel doping engineering as ACD-SOI structure and compared it with a conventional fully-depleted SOI MOSFET (C-SOI) with uniform doping distribution using 2-D ATLAS simulator. The amended channel doping is a vertical graded doping that is distributed from the surface of structure with high doping density to the bottom of channel, near the buried oxide, with low doping density. Short channel effects (SCEs) and leakage current suppress due to high barrier height near the source region and electric field modification in the ACD-SOI in comparison with the C-SOI structure. Furthermore, by lower electric field and electron temperature near the drain region that is the place of hot carrier generation, we except the improvement of reliability and gate induced drain lowering (GIDL) in the proposed structure. Undesirable Self heating effect (SHE) that become a critical challenge for SOI MOSFETs is alleviated in the ACD-SOI structure because of utilizing low doping density near the buried oxide. Thus, refer to accessible results, the ACD-SOI structure with graded distribution in vertical direction is a reliable device especially in low power and high temperature applications.
Cell and plastid division are coordinated through the prereplication factor AtCDT1
Raynaud, Cécile; Perennes, Claudette; Reuzeau, Christophe; Catrice, Olivier; Brown, Spencer; Bergounioux, Catherine
2005-01-01
The cell division cycle involves nuclear and cytoplasmic events, namely organelle multiplication and distribution between the daughter cells. Until now, plastid and plant cell division have been considered as independent processes because they can be uncoupled. Here, down-regulation of AtCDT1a and AtCDT1b, members of the prereplication complex, is shown to alter both nuclear DNA replication and plastid division in Arabidopsis thaliana. These data constitute molecular evidence for relationships between the cell-cycle and plastid division. Moreover, the severe developmental defects observed in AtCDT1-RNA interference (RNAi) plants underline the importance of coordinated cell and organelle division for plant growth and morphogenesis. PMID:15928083
Long-range ordered vorticity patterns in living tissue induced by cell division
NASA Astrophysics Data System (ADS)
Rossen, Ninna S.; Tarp, Jens M.; Mathiesen, Joachim; Jensen, Mogens H.; Oddershede, Lene B.
2014-12-01
In healthy blood vessels with a laminar blood flow, the endothelial cell division rate is low, only sufficient to replace apoptotic cells. The division rate significantly increases during embryonic development and under halted or turbulent flow. Cells in barrier tissue are connected and their motility is highly correlated. Here we investigate the long-range dynamics induced by cell division in an endothelial monolayer under non-flow conditions, mimicking the conditions during vessel formation or around blood clots. Cell divisions induce long-range, well-ordered vortex patterns extending several cell diameters away from the division site, in spite of the system’s low Reynolds number. Our experimental results are reproduced by a hydrodynamic continuum model simulating division as a local pressure increase corresponding to a local tension decrease. Such long-range physical communication may be crucial for embryonic development and for healing tissue, for instance around blood clots.
Targeted Approaches to Overcoming Endocrine Resistance in Breast Cancer
2011-08-01
NM_001012271 BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog AF053305 CDC20 Cell division cycle 20 homolog BG256659 CDC25B Cell division cycle...by benzimidazoles 1 homolog), BIRC5/ Survivin, CDCA8 (cell division cycle-associated protein 8), AURKB (aurora kinase B), CDC25B (cell division cycle
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-29
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Areal Crater Density Analysis of Volcanic Smooth Plains: A New Approach to Distinguishing Age Units
NASA Astrophysics Data System (ADS)
Ostrach, L. R.; Robinson, M. S.
2013-12-01
It is well documented that the lunar maria were emplaced over an extended period of time [e.g., 1-3], and mare units exhibit significant color differences in multispectral data that are interpreted to correlate with distinct mineralogical compositions and ages [e.g., 3-7]. Areal crater density (ACD) analysis is used as a novel approach to identify resurfacing boundaries within Mare Imbrium as a test case for mercurian studies. Absolute model age dating and measures of ACD from crater counts on Lunar Reconnaissance Orbiter Wide Angle Camera (LRO WAC) mosaics reveal two spatially expansive, statistically separable units in Mare Imbrium. The older, spectrally red unit (~15-18 wt% FeO, ~2-5 wt% TiO2 [8]) in the east is ~3.3 Ga, and the younger, spectrally blue unit (~17-20 wt% FeO, ~7-10 wt% TiO2 [8]) in the west is ~2.2 Ga. ACD measurements show a regional boundary at the contact between these two regions. The geologic contact is confidently observed in ACD maps derived for regions with model age differences >300-500 million years and spatial extents >1 × 104 km2. The older, spectrally red unit exhibits higher ACD (>35000 craters with diameters ≥500 m per 106 km2) and the younger, spectrally blue unit has a lower ACD (<26000 craters with diameters ≥500 m per 106 km2); the absolute model ages and ACD results agree with other dating studies of this region [5, 9-12]. Thus, ACD measurements provide a reliable technique to distinguish relative ages among geologic units as well as a means to explore the statistical significance of published absolute model ages. Moreover, the ability to distinguish surface units of different ages from measures of crater frequencies in Mare Imbrium, when spectral information is not available or units do not exhibit spectral contrasts, shows that the ACD technique may be applied to other planetary bodies to search for age boundaries within contiguous smooth plains units. For example, multispectral differences within volcanic units (age and composition) are not observed on Mercury [e.g., 13-15], so the ACD method can be used to test hypotheses concerning timing of smooth plains emplacement [15]. [1] Hartmann W.K. et al. (1981) In: BVTP, 1049-1127. [2] Stöffler D. et al. (2006) Rev. Mineral. Geochem, 60, 519-596. [3] Hiesinger H. et al. (2011) Spec. Pap. - Geol. Soc. Am, 477, 1-51. [4] Pieters C.M. (1978) Proc. Lunar Plan. Sci. Conf, 9th, 2825-2849. [5] Hiesinger H. et al. (2000) J. Geophys. Res, 105, 29239-29275. [6] Staid M.I. and C.M. Pieters (2001) J. Geophys. Res, 106, 27887-27900. [7] Staid M.I. et al. (2011) J. Geophys. Res, 116, E00G10. [8] Lucey P.G. et al. (2000) J. Geophys. Res, 105, 20297-20306. [9] Schaber G.G. (1973) In: Apollo 17 PSR, NASA SP-330, 30-17 to 30-25. [10] Schaber G.G. et al. (1975) The Moon, 13, 395-423. [11] Boyce J.M. and A.L. Dial Jr. (1975) Proc. Lunar Sci. Conf, 6th, 2585-2595. [12] Bugiolacchi R. and J.E. Guest (2008) Icarus, 197, 1-18. [13] Robinson M.S. et al. (2008) Science, 321, 66-69. [14] Denevi B.W. et al. (2009) Science, 324, 613-618. [15] Denevi B.W. et al. (2013) J. Geophys. Res, 118, 1-17.
Chen, Meng; Zhang, Ling; Yang, Bo; Gao, Mingxia; Zhang, Xiangmin
2018-03-01
Alkyne is unique, specific and biocompatible in the Raman-silent region of the cell, but there still remains a challenge to achieve ultrasensitive detection in living systems due to its weak Raman scattering. Herein, a terminal alkyne ((E)-2-[4-(ethynylbenzylidene)amino]ethane-1-thiol (EBAE)) with surface-enhanced Raman scattering is synthesized. The EBAE molecule possesses S- and C-termini, which can be directly bonded to gold nanoparticles and dopamine/silver by forming the Au-S chemical bond and the carbon-metal bond, respectively. The distance between Raman reporter and AuNPs/AgNPs can be reduced, contributing to forming hot-spot-based SERS substrate. The alkyne functionalized nanoparticles are based on Au core and encapsulating polydopamine shell, defined as Au-core and dopamine/Ag-shell (ACDS). The bimetallic ACDS induce strong SERS signals for molecular imaging that arise from the strong electromagnetic field. Furthermore, the EBAE provides a distinct peak in the cellular Raman-silent region with nearly zero background interference. The EBAE Raman signals could be tremendously enhanced when the Raman reporter is located at the middle of the Au-core and dopamine/Ag-shell. Therefore, this work could have huge potential benefits for the highly sensitive detection of intercellular information delivery by connecting the recognition molecules in biomedical diagnostics. Graphical abstract Terminal-alkyne-functionalized Au-core and silver/dopamine-shell nanotags for live-cell surface-enhanced Raman scattering imaging.
Rivkin, Richard B.
1986-01-01
Silicon is an essential element for diatom frustule synthesis and is usually taken up only by dividing cells. With 68Ge, a radioactive analog of Si, the cell cycle marker event of frustule formation was identified for individual species of diatom. The frequency of cells within a population undergoing this division event was estimated, and the cell division rate was calculated. In laboratory cultures, these rates of cell division and those calculated from changes in cell numbers were similar. By dual labeling with 68Ge(OH)4 and NaH14CO3, rates of cell division and photosynthesis were coincidently measured for diatoms both in laboratory cultures and when isolated from natural populations in estuarine, offshore, and polar environments. These techniques permit the coupling between photosynthesis and cell division to be examined in situ for individual species of diatom. PMID:16347039
NASA Astrophysics Data System (ADS)
Shimizu, Takashi; Eguchi, Kentaro; Nishida, Ikuo; Laukens, Kris; Witters, Erwin; van Onckelen, Harry; Nagata, Toshiyuki
2006-06-01
Effects of auxin as plant hormones are widespread; in fact in almost all aspects of plant growth and development auxin plays a pivotal role. Although auxin is required for propagating cell division in plant cells, its effect upon cell division is least understood. If auxin is depleted from the culture medium, cultured cells cease to divide. It has been demonstrated in this context that the addition of auxin to auxin-starved nondividing tobacco BY-2 cells induced semisynchronous cell division. On the other hand, there are some cell lines, named habituated cells, that can grow without auxin. The cause and reason for the habituated cells have not been clarified. A habituated cell line named 2B-13 is derived from the tobacco BY-2 cell line, which has been most intensively studied among plant cell lines. When we tried to find the difference between two cell lines of BY-2 and 2B-13 cells, we found that the addition of culture filtrated from the auxin-habituated 2B-13 cells induced semisynchronous cell division in auxin-starved BY-2 cells. The cell division factor (CDF) that is responsible for inducing cell division in auxin-starved BY-2 cells was purified to near-homogeneity by sequential passage through a hydroxyapatite column, a ConA Sepharose column and a Sephadex gel filtration column. The resulting purified fraction appeared as a single band of high molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels by silver staining and was able to induce cell division in auxin-starved BY-2 cells. Identification of the protein by MALD-TOF-MS/MS revealed that it is structurally related to P-glycoprotein from Gossypioides kirkii, which belongs to ATP-binding cassette (ABC)-transporters. The significance of CDF as a possible ABC-transporter is discussed in relationship to auxin-autotrophic growth and auxin-signaling pathway.
Division Planes Alternate in Spherical Cells of Escherichia coli
Begg, K. J.; Donachie, W. D.
1998-01-01
In the spherical cells of Escherichia coli rodA mutants, division is initiated at a single point, from which a furrow extends progressively around the cell. Using “giant” rodA ftsA cells, we confirmed that each new division furrow is initiated at the midpoint of the previous division plane and runs perpendicular to it. PMID:9573213
The final cut: cell polarity meets cytokinesis at the bud neck in S. cerevisiae.
Juanes, Maria Angeles; Piatti, Simonetta
2016-08-01
Cell division is a fundamental but complex process that gives rise to two daughter cells. It includes an ordered set of events, altogether called "the cell cycle", that culminate with cytokinesis, the final stage of mitosis leading to the physical separation of the two daughter cells. Symmetric cell division equally partitions cellular components between the two daughter cells, which are therefore identical to one another and often share the same fate. In many cases, however, cell division is asymmetrical and generates two daughter cells that differ in specific protein inheritance, cell size, or developmental potential. The budding yeast Saccharomyces cerevisiae has proven to be an excellent system to investigate the molecular mechanisms governing asymmetric cell division and cytokinesis. Budding yeast is highly polarized during the cell cycle and divides asymmetrically, producing two cells with distinct sizes and fates. Many components of the machinery establishing cell polarization during budding are relocalized to the division site (i.e., the bud neck) for cytokinesis. In this review we recapitulate how budding yeast cells undergo polarized processes at the bud neck for cell division.
Li, Yingzi; Naveed, Hammad; Kachalo, Sema; Xu, Lisa X.; Liang, Jie
2014-01-01
Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation. PMID:24504016
Quantifying cell turnover using CFSE data.
Ganusov, Vitaly V; Pilyugin, Sergei S; de Boer, Rob J; Murali-Krishna, Kaja; Ahmed, Rafi; Antia, Rustom
2005-03-01
The CFSE dye dilution assay is widely used to determine the number of divisions a given CFSE labelled cell has undergone in vitro and in vivo. In this paper, we consider how the data obtained with the use of CFSE (CFSE data) can be used to estimate the parameters determining cell division and death. For a homogeneous cell population (i.e., a population with the parameters for cell division and death being independent of time and the number of divisions cells have undergone), we consider a specific biologically based "Smith-Martin" model of cell turnover and analyze three different techniques for estimation of its parameters: direct fitting, indirect fitting and rescaling method. We find that using only CFSE data, the duration of the division phase (i.e., approximately the S+G2+M phase of the cell cycle) can be estimated with the use of either technique. In some cases, the average division or cell cycle time can be estimated using the direct fitting of the model solution to the data or by using the Gett-Hodgkin method [Gett A. and Hodgkin, P. 2000. A cellular calculus for signal integration by T cells. Nat. Immunol. 1:239-244]. Estimation of the death rates during commitment to division (i.e., approximately the G1 phase of the cell cycle) and during the division phase may not be feasible with the use of only CFSE data. We propose that measuring an additional parameter, the fraction of cells in division, may allow estimation of all model parameters including the death rates during different stages of the cell cycle.
A single-cell pedigree analysis of alternative stochastic lymphocyte fates
Hawkins, E. D.; Markham, J. F.; McGuinness, L. P.; Hodgkin, P. D.
2009-01-01
In contrast to most stimulated lymphocytes, B cells exposed to Toll-like receptor 9 ligands are nonself-adherent, allowing individual cells and families to be followed in vitro for up to 5 days. These B cells undergo phases typical of an adaptive response, dividing up to 6 times before losing the impetus for further growth and division and eventually dying by apoptosis. Using long-term microscopic imaging, accurate histories of individual lymphocyte fates were collected. Quantitative analysis of family relationships revealed that times to divide of siblings were strongly related but these correlations were progressively lost through consecutive divisions. A weaker, but significant, correlation was also found for death times among siblings. Division cessation is characterized by a loss of cell growth and the division in which this occurs is strongly inherited from the original founder cell and is related to the size this cell reaches before its first division. Thus, simple division-based dilution of factors synthesized during the first division may control the maximum division reached by stimulated cells. The stochastic distributions of times to divide, times to die, and divisions reached are also measured. Together, these results highlight the internal cellular mechanisms that control immune responses and provide a foundation for the development of new mathematical models that are correct at both single-cell and population levels. PMID:19633185
The report summarizes the progress in the design and construction of automatic equipment for synchronizing cell division in culture by periodic...Concurrent experiments in hypothermic synchronization of algal cell division are reported.
Gravity and the orientation of cell division
NASA Technical Reports Server (NTRS)
Helmstetter, C. E.
1997-01-01
A novel culture system for mammalian cells was used to investigate division orientations in populations of Chinese hamster ovary cells and the influence of gravity on the positioning of division axes. The cells were tethered to adhesive sites, smaller in diameter than a newborn cell, distributed over a nonadhesive substrate positioned vertically. The cells grew and divided while attached to the sites, and the angles and directions of elongation during anaphase, projected in the vertical plane, were found to be random with respect to gravity. However, consecutive divisions of individual cells were generally along the same axis or at 90 degrees to the previous division, with equal probability. Thus, successive divisions were restricted to orthogonal planes, but the choice of plane appeared to be random, unlike the ordered sequence of cleavage orientations seen during early embryo development.
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Mandakovic, Dinka; Trigo, Carla; Andrade, Derly; Riquelme, Brenda; Gómez-Lillo, Gabriela; Soto-Liebe, Katia; Díez, Beatriz; Vásquez, Mónica
2016-01-01
Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120.
Evaluation of Anterior Segment Parameters in Obesity
Uzun, Feyzahan; Karaca, Emine Esra; Kalaycı, Mustafa
2015-01-01
Purpose To investigate anterior segment parameters in obese patients in comparison to healthy individuals. Methods Thirty-four obese subjects and 34 age-sex-matched healthy subjects were enrolled in this prospective cross-sectional study. Ophthalmological examinations including intraocular pressure (IOP), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), and axial length (AL) measurements were performed on each subject. Height and weight of all subjects were recorded and body mass index (BMI) was calculated. Results IOP was significantly higher in the obese group (p = 0.003). The mean ACD in obese subjects was significantly lower than that in control subjects (p = 0.036). AL, ACV, ACA and CCT were not significantly different between the groups. There was a positive correlation between BMI and IOP (r = 0.404, p < 0.001). ACD and ACA were negatively correlated with BMI. Conclusions IOP was significantly higher and ACD was significantly lower in obese subjects. AL, ACV, ACA and CCT were not significantly different between the groups. The impact of obesity on anterior chamber parameters should be further investigated. PMID:26240505
The stem cell division theory of cancer.
López-Lázaro, Miguel
2018-03-01
All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and lung cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations and epigenetic mistakes occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy. Copyright © 2018 Elsevier B.V. All rights reserved.
Ultrasonography and optical low-coherence interferometry compared in the chicken eye.
Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank; Feldkaemper, Marita P
2012-06-01
To compare ocular biometry [anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL)] using A-scan ultrasonography and optical low-coherence interferometry (OLCI) in the chicken eye. Two-week-old chicks (n = 42) were measured. Bland-Altman plots and repeatability and correlation analyses were calculated for both methods. There was a high correlation between both methods for ACD (r = 0.6144, p < 0.0001), VCD (r = 0.9595, p < 0.0001), and AL (r = 0.9290, p < 0.0001) but not for LT (r = 0.1604, p = 0.144). Measurements by OLCI were more consistent (smaller coefficients of variation and higher intraclass correlation). Bland-Altman plots showed that ultrasound provided larger values for LT, VCD, and AL but not for ACD [differences between ultrasound and OLCI (mean ± SD): ACD = -0.11 ± 0.12 mm; LT = 0.10 ± 0.09 mm; VCD = 0.25 ± 0.08 mm; AL = 0.50 ± 0.16 mm]. A high correlation between both techniques was found for three of the four parameters (ACD, VCD, and AL). However, as the absolute values were different, both techniques cannot replace each other mainly because (1) one is non-contact and the other contact and can induce a minor indentation of the cornea and (2) each device uses different types of waves that cross the ocular interfaces differently. While consistency and repeatability were better by OLCI, a disadvantage is that, different from humans, it can only be used in anesthetized chicks.
Improved accuracy of intraocular lens power calculation with the Zeiss IOLMaster.
Olsen, Thomas
2007-02-01
This study aimed to demonstrate how the level of accuracy in intraocular lens (IOL) power calculation can be improved with optical biometry using partial optical coherence interferometry (PCI) (Zeiss IOLMaster) and current anterior chamber depth (ACD) prediction algorithms. Intraocular lens power in 461 consecutive cataract operations was calculated using both PCI and ultrasound and the accuracy of the results of each technique were compared. To illustrate the importance of ACD prediction per se, predictions were calculated using both a recently published 5-variable method and the Haigis 2-variable method and the results compared. All calculations were optimized in retrospect to account for systematic errors, including IOL constants and other off-set errors. The average absolute IOL prediction error (observed minus expected refraction) was 0.65 dioptres with ultrasound and 0.43 D with PCI using the 5-variable ACD prediction method (p < 0.00001). The number of predictions within +/- 0.5 D, +/- 1.0 D and +/- 2.0 D of the expected outcome was 62.5%, 92.4% and 99.9% with PCI, compared with 45.5%, 77.3% and 98.4% with ultrasound, respectively (p < 0.00001). The 2-variable ACD method resulted in an average error in PCI predictions of 0.46 D, which was significantly higher than the error in the 5-variable method (p < 0.001). The accuracy of IOL power calculation can be significantly improved using calibrated axial length readings obtained with PCI and modern IOL power calculation formulas incorporating the latest generation ACD prediction algorithms.
Frascone, Ralph J; Wayne, Marvin A; Swor, Robert A; Mahoney, Brian D; Domeier, Robert M; Olinger, Michael L; Tupper, David E; Setum, Cindy M; Burkhart, Nathan; Klann, Lucinda; Salzman, Joshua G; Wewerka, Sandi S; Yannopoulos, Demetris; Lurie, Keith G; O'Neil, Brian J; Holcomb, Richard G; Aufderheide, Tom P
2013-09-01
A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD+ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the etiology. This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (Modified Rankin Scale score ≤ 3). Between October 2005 and July 2009, 2738 patients were enrolled (S-CPR=1335; ACD+ITD=1403). Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p=0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p=0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD, regardless of the etiology of the cardiac arrest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Udassi, Jai P.; Udassi, Sharda; Lamb, Melissa A.; Lamb, Kenneth E.; Theriaque, Douglas W.; Shuster, Jonathan J.; Zaritsky, Arno L.; Haque, Ikram U.
2013-01-01
Objective We developed an adhesive glove device (AGD) to perform ACD-CPR in pediatric manikins, hypothesizing that AGD-ACD-CPR provides better chest decompression compared to standard (S)-CPR. Design Split-plot design randomizing 16 subjects to test four manikin-technique models in a crossover fashion to AGD-ACD-CPR vs. S-CPR. Healthcare providers performed 5 min of CPR with 30:2 compression:ventilation ratio in the four manikin models: (1) adolescent; (2) child two-hand; (3) child one-hand; and (4) infant two-thumb. Methods Modified manikins recorded compression pressure (CP), compression depth (CD) and decompression depth (DD). The AGD consisted of a modified oven mitt with an adjustable strap; a Velcro patch was sewn to the palmer aspect. The counter Velcro patch was bonded to the anterior chest wall. For infant CPR, the thumbs of two oven mitts were stitched together with Velcro. Subjects were asked to actively pull up during decompression. Subjects’ heart rate (HR), respiratory rate (RR) and recovery time (RT) for HR/RR to return to baseline were recorded. Subjects were blinded to data recordings. Data (mean ± SEM) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as P ≤ 0.05. Results Mean decompression depth difference was significantly greater with AGD-ACD-CPR compared to S-CPR; 38–75% of subjects achieved chest decompression to or beyond baseline. AGD-ACD-CPR provided 6–12% fewer chest compressions/minute than S-CPR group. There was no significant difference in CD, CP, HR, RR and RT within each group comparing both techniques. Conclusion A simple, inexpensive glove device for ACD-CPR improved chest decompression with emphasis on active pull in manikins without excessive rescuer fatigue. The clinical implication of fewer compressions/minute in the AGD group needs to be evaluated. PMID:19683849
Taffon, Pierluigi; Rossi, Gabriele; Kindermans, Jean-Marie; Van den Bergh, Rafael; Nguon, Chea; Debackere, Mark; Vernaeve, Lieven; De Smet, Martin; Venables, Emilie
2018-01-01
Pro-active case detection (Pro-ACD), in the form of voluntary screening and treatment (VSAT) following community mobilisation about 'asymptomatic malaria', is currently being evaluated as a tool for Plasmodium falciparum elimination in Preah Vihear Province, Cambodia. A qualitative study was conducted to explore community understanding, perceptions, expectations and acceptability of the Pro-ACD intervention in order to identify aspects that could be improved in future Pro-ACD activities. This was ancillary to a three-round VSAT campaign, carried out in three villages between December 2015 and March 2016. Qualitative data collection began shortly after the end of the three rounds of screening. Purposive sampling was used to select participants. Nine focus group discussions with participants (n = 46) and non-participants (n = 40) in the Pro-ACD screening were conducted, in addition to in-depth interviews with key village figures (n = 9). Health promotion messages were well delivered and received, but it was difficult for many villagers to understand the messages around 'asymptomatic malaria'. Overall, villagers and village leaders had a positive opinion about the VSAT intervention. Acceptability was high, as a direct consequence of favourable perceptions towards the screening activity: the Pro-ACD intervention was seen by the local population as an effective, inexpensive, reliable and readily available tool to protect individuals and the community from the insurgence of malaria. Physical absence and lack of time (both linked to work-related activities) were the main reasons for non-participation. Although VSAT was generally well perceived and accepted, the 'time factor' related to the need to satisfy essential daily subsistence requirements played a significant role in determining participation in the screening. More well-adapted and meaningful Pro-ACD approaches could be implemented by improving the timing of the testing activites, and strengthening community participation and engagement to increase acceptability.
Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in childhood asthma.
Rabinovitch, Nathan; Graber, Nora J; Chinchilli, Vernon M; Sorkness, Christine A; Zeiger, Robert S; Strunk, Robert C; Bacharier, Leonard B; Martinez, Fernando D; Szefler, Stanley J
2010-09-01
A subset of children with asthma respond better to leukotriene receptor antagonists than to inhaled corticosteroids. Information is needed to identify children with these preferential responses. We sought to determine whether the ratio of urinary leukotriene E(4) (LTE(4)) to fractional exhaled nitric oxide (FE(NO)) delineates children with preferential responsiveness to montelukast compared with fluticasone propionate (FP) therapy. Data from 318 children with mild-to-moderate asthma enrolled in 2 National Heart, Lung, and Blood Institute Childhood Asthma Research and Education Network studies (Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid [CLIC] and the Pediatric Asthma Controller Trial [PACT]) were analyzed. The association between LTE(4)/FE(NO) ratios at baseline and improved lung function or asthma control days (ACDs) with montelukast and FP therapy was determined, and phenotypic characteristics related to high ratios were assessed. LTE(4)/FE(NO) ratios were associated with a greater response to montelukast than FP therapy for FEV(1) measurements (2.1% increase per doubling of ratio, P = .001) and for ACDs per week (0.3-ACD increase, P = .009) in the CLIC study. In PACT the ratio was associated with greater ACD responsiveness to MT than FP therapy (0.6 ACD increase, P=.03) [corrected]. In a combined study analysis, LTE(4): FE(NO) ratios were associated with greater response to MT than FP therapy for FEV(1) (1.8% increase, P =.0005) and ACDs (0.4 increase, P =.001)[corrected].Children with LTE(4)/FE(NO) ratios at or above the 75th percentile were likely (P < .05) to be younger and female and exhibit lower levels of atopic markers and methacholine reactivity. LTE(4)/FE(NO) ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma. Copyright (C) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Frascone, Ralph J; Wayne, Marvin A; Swor, Robert A; Mahoney, Brian D; Domeier, Robert M; Olinger, Michael L; Tupper, David E; Setum, Cindy M; Burkhart, Nathan; Klann, Lucinda; Salzman, Joshua G; Wewerka, Sandi S; Yannopoulos, Demetris; Lurie, Keith G; O’Neil, Brian J.; Holcomb, Richard G; Aufderheide, Tom P
2013-01-01
Background A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD+ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the aetiology. Methods This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (modified Rankin Scale score ≤3). Results Between October 2005 to July 2009, 2738 patients were enrolled (S-CPR = 1335; ACD+ITD =1403). Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p=0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p=0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Conclusions Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD, regardless of the etiology of the cardiac arrest. Clinical Trial Registration NCT 00189423 (http://www.clinicaltrials.gov) PMID:23669489
Huang, S; Law, P; Francis, K; Palsson, B O; Ho, A D
1999-10-15
We have developed a time-lapse camera system to follow the replication history and the fate of hematopoietic stem cells (HSC) at a single-cell level. Combined with single-cell culture, we correlated the early replication behavior with colony development after 14 days. The membrane dye PKH26 was used to monitor cell division. In addition to multiple, synchronous, and symmetric divisions, single-sorted CD34(+)/CD38(-) cells derived from fetal liver (FLV) also gave rise to a daughter cell that remained quiescent for up to 8 days, whereas the other daughter cell proliferated exponentially. Upon separation and replating as single cells onto medium containing a cytokine cocktail, 60.6% +/- 9.8% of the initially quiescent cells (PKH26 bright) gave rise again to colonies and 15.8% +/- 7.8% to blast colonies that could be replated. We have then determined the effects of various regulatory molecules on symmetry of initial cell divisions. After single-cell sorting, the CD34(+)/CD38(-) cells derived from FLV were exposed to flt3-ligand, thrombopoietin, stem cell factor (SCF), or medium containing a cytokine cocktail (with SCF, interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor, and erythropoietin). Whereas mitotic rate, colony efficiency, and asymmetric divisions could be altered using various regulatory molecules, the asymmetric division index, defined as the number of asymmetric divisions versus the number of dividing cells, was not altered significantly. This observation suggests that, although lineage commitment and cell proliferation can be skewed by extrinsic signaling, symmetry of early divisions is probably under the control of intrinsic factors.
Luo, Xu-rui; Zhang, Hui-li; Chen, Geng-jin; Ding, Wen-shu; Huang, Liang
2013-01-01
BACKGROUND: Active compression-decompression cardiopulmonary resuscitation (ACDCPR) has been popular in the treatment of patients with cardiac arrest (CA). However, the effect of ACD-CPR versus conventional standard CPR (S-CRP) is contriversial. This study was to analyze the efficacy and safety of ACD-CPR versus S-CRP in treating CA patients. METHODS: Randomized or quasi-randomized controlled trials published from January 1990 to March 2011 were searched with the phrase “active compression-decompression cardiopulmonary resuscitation and cardiac arrest” in PubMed, EmBASE, and China Biomedical Document Databases. The Cochrane Library was searched for papers of meta-analysis. Restoration of spontaneous circulation (ROSC) rate, survival rate to hospital admission, survival rate at 24 hours, and survival rate to hospital discharge were considered primary outcomes, and complications after CPR were viewed as secondary outcomes. Included studies were critically appraised and estimates of effects were calculated according to the model of fixed or random effects. Inconsistency across the studies was evaluated using the I2 statistic method. Sensitivity analysis was made to determine statistical heterogeneity. RESULTS: Thirteen studies met the criteria for this meta-analysis. The studies included 396 adult CA patients treated by ACD-CPR and 391 patients by S-CRP. Totally 234 CA patients were found out hospitals, while the other 333 CA patients were in hospitals. Two studies were evaluated with high-quality methodology and the rest 11 studies were of poor quality. ROSC rate, survival rate at 24 hours and survival rate to hospital discharge with favorable neurological function indicated that ACD-CPR is superior to S-CRP, with relative risk (RR) values of 1.39 (95% CI 0.99–1.97), 1.94 (95% CI 1.45–2.59) and 2.80 (95% CI 1.60–5.24). No significant differences were found in survival rate to hospital admission and survival rate to hospital discharge for ACD-CPR versus S-CRP with RR values of 1.06 (95% CI 0.76–1.60) and 1.00 (95% CI 0.73–1.38). CONCLUSION: Quality controlled studies confirmed the superiority of ACD-CPR to S-CRP in terms of ROSC rate and survival rate at 24 hours. Compared with S-CRP, ACD-CPR could not improve survival rate to hospital admission or survival rate to hospital discharge. PMID:25215130
Zhang, Jia-Hua; He, Yan-Li; Zhu, Rui; Du, Wen; Xiao, Jun-Hua
2017-06-01
Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated. In this study, our data showed that cell division cycle protein 6 expression was significantly upregulated in primary chronic myeloid leukemia cells and the chronic myeloid leukemia cell line K562 cells, as compared to the normal bone marrow mononuclear cells. BCR/ABL kinase inhibitor STI571 or BCR/ABL small interfering RNA could significantly downregulate cell division cycle protein 6 messenger RNA expression in K562 cells. Moreover, phosphoinositide 3-kinase/AKT pathway inhibitor LY294002 and Janus kinase/signal transducer and activator of transcription pathway inhibitor AG490 could downregulate cell division cycle protein 6 expression in K562 cells, but not RAS/mitogen-activated protein kinase pathway inhibitor PD98059 had such effect. Cell division cycle protein 6 gene silencing by small interfering RNA effectively resulted in decrease of proliferation, increase of apoptosis, and arrest of cell cycle in K562 cells. These findings have demonstrated that cell division cycle protein 6 overexpression may contribute to the high proliferation and low apoptosis in chronic myeloid leukemia cells and can be regulated by BCR/ABL signal transduction through downstream phosphoinositide 3-kinase/Akt and Janus kinase/signal transducer and activator of transcription pathways, suggesting cell division cycle protein 6 as a potential therapeutic target in chronic myeloid leukemia.
Wong, Ming-Kin; Guan, Daogang; Ng, Kaoru Hon Chun; Ho, Vincy Wing Sze; An, Xiaomeng; Li, Runsheng; Ren, Xiaoliang
2016-01-01
Metazoan development demands not only precise cell fate differentiation but also accurate timing of cell division to ensure proper development. How cell divisions are temporally coordinated during development is poorly understood. Caenorhabditis elegans embryogenesis provides an excellent opportunity to study this coordination due to its invariant development and widespread division asynchronies. One of the most pronounced asynchronies is a significant delay of cell division in two endoderm progenitor cells, Ea and Ep, hereafter referred to as E2, relative to its cousins that mainly develop into mesoderm organs and tissues. To unravel the genetic control over the endoderm-specific E2 division timing, a total of 822 essential and conserved genes were knocked down using RNAi followed by quantification of cell cycle lengths using in toto imaging of C. elegans embryogenesis and automated lineage. Intriguingly, knockdown of numerous genes encoding the components of general transcription pathway or its regulatory factors leads to a significant reduction in the E2 cell cycle length but an increase in cell cycle length of the remaining cells, indicating a differential requirement of transcription for division timing between the two. Analysis of lineage-specific RNA-seq data demonstrates an earlier onset of transcription in endoderm than in other germ layers, the timing of which coincides with the birth of E2, supporting the notion that the endoderm-specific delay in E2 division timing demands robust zygotic transcription. The reduction in E2 cell cycle length is frequently associated with cell migration defect and gastrulation failure. The results suggest that a tissue-specific transcriptional activation is required to coordinate fate differentiation, division timing, and cell migration to ensure proper development. PMID:27056332
Alignment of cell division axes in directed epithelial cell migration
NASA Astrophysics Data System (ADS)
Marel, Anna-Kristina; Podewitz, Nils; Zorn, Matthias; Oskar Rädler, Joachim; Elgeti, Jens
2014-11-01
Cell division is an essential dynamic event in tissue remodeling during wound healing, cancer and embryogenesis. In collective migration, tensile stresses affect cell shape and polarity, hence, the orientation of the cell division axis is expected to depend on cellular flow patterns. Here, we study the degree of orientation of cell division axes in migrating and resting epithelial cell sheets. We use microstructured channels to create a defined scenario of directed cell invasion and compare this situation to resting but proliferating cell monolayers. In experiments, we find a strong alignment of the axis due to directed flow while resting sheets show very weak global order, but local flow gradients still correlate strongly with the cell division axis. We compare experimental results with a previously published mesoscopic particle based simulation model. Most of the observed effects are reproduced by the simulations.
Asymmetries in Cell Division, Cell Size, and Furrowing in the Xenopus laevis Embryo.
Tassan, Jean-Pierre; Wühr, Martin; Hatte, Guillaume; Kubiak, Jacek
2017-01-01
Asymmetric cell divisions produce two daughter cells with distinct fate. During embryogenesis, this mechanism is fundamental to build tissues and organs because it generates cell diversity. In adults, it remains crucial to maintain stem cells. The enthusiasm for asymmetric cell division is not only motivated by the beauty of the mechanism and the fundamental questions it raises, but has also very pragmatic reasons. Indeed, misregulation of asymmetric cell divisions is believed to have dramatic consequences potentially leading to pathogenesis such as cancers. In diverse model organisms, asymmetric cell divisions result in two daughter cells, which differ not only by their fate but also in size. This is the case for the early Xenopus laevis embryo, in which the two first embryonic divisions are perpendicular to each other and generate two pairs of blastomeres, which usually differ in size: one pair of blastomeres is smaller than the other. Small blastomeres will produce embryonic dorsal structures, whereas the larger pair will evolve into ventral structures. Here, we present a speculative model on the origin of the asymmetry of this cell division in the Xenopus embryo. We also discuss the apparently coincident asymmetric distribution of cell fate determinants and cell-size asymmetry of the 4-cell stage embryo. Finally, we discuss the asymmetric furrowing during epithelial cell cytokinesis occurring later during Xenopus laevis embryo development.
Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP.
Beilharz, Katrin; Nováková, Linda; Fadda, Daniela; Branny, Pavel; Massidda, Orietta; Veening, Jan-Willem
2012-04-10
How the human pathogen Streptococcus pneumoniae coordinates cell-wall synthesis during growth and division to achieve its characteristic oval shape is poorly understood. The conserved eukaryotic-type Ser/Thr kinase of S. pneumoniae, StkP, previously was reported to phosphorylate the cell-division protein DivIVA. Consistent with a role in cell division, GFP-StkP and its cognate phosphatase, GFP-PhpP, both localize to the division site. StkP localization depends on its penicillin-binding protein and Ser/Thr-associated domains that likely sense uncross-linked peptidoglycan, because StkP and PhpP delocalize in the presence of antibiotics that target the latest stages of cell-wall biosynthesis and in cells that have stopped dividing. Time-lapse microscopy shows that StkP displays an intermediate timing of recruitment to midcell: StkP arrives shortly after FtsA but before DivIVA. Furthermore, StkP remains at midcell longer than FtsA, until division is complete. Cells mutated for stkP are perturbed in cell-wall synthesis and display elongated morphologies with multiple, often unconstricted, FtsA and DivIVA rings. The data show that StkP plays an important role in regulating cell-wall synthesis and controls correct septum progression and closure. Overall, our results indicate that StkP signals information about the cell-wall status to key cell-division proteins and in this way acts as a regulator of cell division.
Chromosome segregation drives division site selection in Streptococcus pneumoniae.
van Raaphorst, Renske; Kjos, Morten; Veening, Jan-Willem
2017-07-18
Accurate spatial and temporal positioning of the tubulin-like protein FtsZ is key for proper bacterial cell division. Streptococcus pneumoniae (pneumococcus) is an oval-shaped, symmetrically dividing opportunistic human pathogen lacking the canonical systems for division site control (nucleoid occlusion and the Min-system). Recently, the early division protein MapZ was identified and implicated in pneumococcal division site selection. We show that MapZ is important for proper division plane selection; thus, the question remains as to what drives pneumococcal division site selection. By mapping the cell cycle in detail, we show that directly after replication both chromosomal origin regions localize to the future cell division sites, before FtsZ. Interestingly, Z-ring formation occurs coincidently with initiation of DNA replication. Perturbing the longitudinal chromosomal organization by mutating the condensin SMC, by CRISPR/Cas9-mediated chromosome cutting, or by poisoning DNA decatenation resulted in mistiming of MapZ and FtsZ positioning and subsequent cell elongation. Together, we demonstrate an intimate relationship between DNA replication, chromosome segregation, and division site selection in the pneumococcus, providing a simple way to ensure equally sized daughter cells.
Li, Yubing; Liu, Dianyi; López-Paz, Cristina; Olson, Bradley JSC; Umen, James G
2016-01-01
Proliferating cells actively control their size by mechanisms that are poorly understood. The unicellular green alga Chlamydomonas reinhardtii divides by multiple fission, wherein a ‘counting’ mechanism couples mother cell-size to cell division number allowing production of uniform-sized daughters. We identified a sizer protein, CDKG1, that acts through the retinoblastoma (RB) tumor suppressor pathway as a D-cyclin-dependent RB kinase to regulate mitotic counting. Loss of CDKG1 leads to fewer mitotic divisions and large daughters, while mis-expression of CDKG1 causes supernumerous mitotic divisions and small daughters. The concentration of nuclear-localized CDKG1 in pre-mitotic cells is set by mother cell size, and its progressive dilution and degradation with each round of cell division may provide a link between mother cell-size and mitotic division number. Cell-size-dependent accumulation of limiting cell cycle regulators such as CDKG1 is a potentially general mechanism for size control. DOI: http://dx.doi.org/10.7554/eLife.10767.001 PMID:27015111
A crucial step in cell division identified | Center for Cancer Research
When cell division doesn’t go according to plan, the resulting daughter cells can become unstable or even cancerous. A team of CCR investigators has now discovered a crucial step required for normal cell division to occur. Read more...
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2013-10-29
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) Cancellation: This notice... Information: Gayle Hickman, Committee Management Specialist, Office Chief of Staff, CDC, 1600 Clifton Road [email protected]cdc.gov . This notice is published less than the required 15 days prior to the start of the announced...
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2010-09-01
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Murphy, David Patrick; Calef, Matthew Thomas
We assess the ability of variants of anomalous change detection (ACD) to identify human activity associated with large outdoor music festivals as they are seen from synthetic aperture radar (SAR) imagery collected by the Sentinel-1 satellite constellation. We found that, with appropriate feature vectors, ACD using random-forest machine learning was most effective at identifying changes associated with the human activity.
All Tumor Cells Are Not Created Equal | Center for Cancer Research
Cell division is commonly thought of as a process whereby one cell gives rise to two identical daughter cells. However, rare cell divisions are asymmetric, generating daughter cells that may differ in size, developmental potential, or even DNA content. The ability of stem cells to undergo asymmetric division allows them to self-renew while simultaneously generate daughter
Mechanical Forces Program the Orientation of Cell Division during Airway Tube Morphogenesis.
Tang, Zan; Hu, Yucheng; Wang, Zheng; Jiang, Kewu; Zhan, Cheng; Marshall, Wallace F; Tang, Nan
2018-02-05
Oriented cell division plays a key role in controlling organogenesis. The mechanisms for regulating division orientation at the whole-organ level are only starting to become understood. By combining 3D time-lapse imaging, mouse genetics, and mathematical modeling, we find that global orientation of cell division is the result of a combination of two types of spindles with distinct spindle dynamic behaviors in the developing airway epithelium. Fixed spindles follow the classic long-axis rule and establish their division orientation before metaphase. In contrast, rotating spindles do not strictly follow the long-axis rule and determine their division orientation during metaphase. By using both a cell-based mechanical model and stretching-lung-explant experiments, we showed that mechanical force can function as a regulatory signal in maintaining the stable ratio between fixed spindles and rotating spindles. Our findings demonstrate that mechanical forces, cell geometry, and oriented cell division function together in a highly coordinated manner to ensure normal airway tube morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.
The Interplay between Cell Wall Mechanical Properties and the Cell Cycle in Staphylococcus aureus
Bailey, Richard G.; Turner, Robert D.; Mullin, Nic; Clarke, Nigel; Foster, Simon J.; Hobbs, Jamie K.
2014-01-01
The nanoscale mechanical properties of live Staphylococcus aureus cells during different phases of growth were studied by atomic force microscopy. Indentation to different depths provided access to both local cell wall mechanical properties and whole-cell properties, including a component related to cell turgor pressure. Local cell wall properties were found to change in a characteristic manner throughout the division cycle. Splitting of the cell into two daughter cells followed a local softening of the cell wall along the division circumference, with the cell wall on either side of the division circumference becoming stiffer. Once exposed, the newly formed septum was found to be stiffer than the surrounding, older cell wall. Deeper indentations, which were affected by cell turgor pressure, did not show a change in stiffness throughout the division cycle, implying that enzymatic cell wall remodeling and local variations in wall properties are responsible for the evolution of cell shape through division. PMID:25468333
Cytokinesis-Based Constraints on Polarized Cell Growth in Fission Yeast
Bohnert, K. Adam; Gould, Kathleen L.
2012-01-01
The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in the ensuing cell cycle. Complete loss or targeted disruption of the non-essential cytokinesis protein Fic1 at the division site, but not at interphase cell tips, resulted in many cells failing to grow at new ends created by cell division. This appeared due to faulty disassembly and abnormal persistence of the cell division machinery at new ends of fic1Δ cells. Moreover, additional mutants defective in the final stages of cytokinesis exhibited analogous growth polarity defects, supporting that robust completion of cell division contributes to new end-growth competency. To test this model, we genetically manipulated S. pombe cells to undergo new end take-off immediately after cell division. Intriguingly, such cells elongated constitutively at new ends unless cytokinesis was perturbed. Thus, cell division imposes constraints that partially override positive controls on growth. We posit that such constraints facilitate invasive fungal growth, as cytokinesis mutants displaying bipolar growth defects formed numerous pseudohyphae. Collectively, these data highlight a role for previous cell cycles in defining a cell's capacity to polarize at specific sites, and they additionally provide insight into how a unicellular yeast can transition into a quasi-multicellular state. PMID:23093943
Cell division plane orientation based on tensile stress in Arabidopsis thaliana
Louveaux, Marion; Julien, Jean-Daniel; Mirabet, Vincent; Boudaoud, Arezki; Hamant, Olivier
2016-01-01
Cell geometry has long been proposed to play a key role in the orientation of symmetric cell division planes. In particular, the recently proposed Besson–Dumais rule generalizes Errera’s rule and predicts that cells divide along one of the local minima of plane area. However, this rule has been tested only on tissues with rather local spherical shape and homogeneous growth. Here, we tested the application of the Besson–Dumais rule to the divisions occurring in the Arabidopsis shoot apex, which contains domains with anisotropic curvature and differential growth. We found that the Besson–Dumais rule works well in the central part of the apex, but fails to account for cell division planes in the saddle-shaped boundary region. Because curvature anisotropy and differential growth prescribe directional tensile stress in that region, we tested the putative contribution of anisotropic stress fields to cell division plane orientation at the shoot apex. To do so, we compared two division rules: geometrical (new plane along the shortest path) and mechanical (new plane along maximal tension). The mechanical division rule reproduced the enrichment of long planes observed in the boundary region. Experimental perturbation of mechanical stress pattern further supported a contribution of anisotropic tensile stress in division plane orientation. Importantly, simulations of tissues growing in an isotropic stress field, and dividing along maximal tension, provided division plane distributions comparable to those obtained with the geometrical rule. We thus propose that division plane orientation by tensile stress offers a general rule for symmetric cell division in plants. PMID:27436908
THE HEMOGLOBIN FUNCTION OF BLOOD AT 4C.
depends on the red cell concentration of 2,3- diphosphoglycerate (2,3-DPG), this metabolic intermediate was assayed and oxygen dissociation curves...the storage period in blood stored in CPD than in ACD. If adenine was present the p50 and 2,3-DPG levels declined more rapidly. However, adenine and...inosine in CPD-stored blood allowed the p50 and 2,3-DPG to persist at near normal levels for most of the 3-week storage period. (Author)
All Tumor Cells Are Not Created Equal | Center for Cancer Research
Cell division is commonly thought of as a process whereby one cell gives rise to two identical daughter cells. However, rare cell divisions are asymmetric, generating daughter cells that may differ in size, developmental potential, or even DNA content. The ability of stem cells to undergo asymmetric division allows them to self-renew while simultaneously generate daughter cells committed to differentiating into specialized cell types.
Ohkusu-Tsukada, Kozo; Ito, Daiki; Okuno, Yuki; Tsukada, Teruyo; Takahashi, Kimimasa
2018-02-07
We recently advocated in favour of naming a novel H2-haplotype consisting of K d , D/L dm7 , I-A k and I-E k in the atopic dermatitis (AD) mouse model NC/Nga as "H-2 nc ." The role of the H2-haplotype in AD development was investigated in H2 b -congenic NC/Nga mice (NC.h2 b/b and NC.h2 b/nc ) established by backcrossing. A severe 2,4-dinitrofluorobenzene (DNFB)-induced dermatitis in NC/Nga was alleviated partially in NC.h2 b/nc and significantly in NC.h2 b/b . The AD phenotype was correlated with thymic stromal lymphopoietin (TSLP)-epidermal expression levels and serum levels of total IgE and IL-18/IL-33. Histologically, allergic contact dermatitis (ACD) was accompanied by lymphocytes and plasma cells-infiltrating perivasculitis in NC.h2 b/nc and NC.h2 b/b and clearly differed from AD accompanied by neutrophils, eosinophils and macrophages-infiltrating diffuse suppurative dermatitis in NC/Nga. Interestingly, IFN-γ/IL-17 production from autoreactive CD4 + T-cells remarkably increased in DNFB-sensitised NC.h2 b/b but not in NC/Nga. Our findings suggest that AD or ACD may depend on haplotype H-2 nc or H-2 b , respectively, in addition to the NC/Nga genetic background.
Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.
Moore, Darcie L; Jessberger, Sebastian
2017-01-01
Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Wollman, Adam J. M.; Miller, Helen; Foster, Simon; Leake, Mark C.
2016-10-01
Staphylococcus aureus is an important pathogen, giving rise to antimicrobial resistance in cell strains such as Methicillin Resistant S. aureus (MRSA). Here we report an image analysis framework for automated detection and image segmentation of cells in S. aureus cell clusters, and explicit identification of their cell division planes. We use a new combination of several existing analytical tools of image analysis to detect cellular and subcellular morphological features relevant to cell division from millisecond time scale sampled images of live pathogens at a detection precision of single molecules. We demonstrate this approach using a fluorescent reporter GFP fused to the protein EzrA that localises to a mid-cell plane during division and is involved in regulation of cell size and division. This image analysis framework presents a valuable platform from which to study candidate new antimicrobials which target the cell division machinery, but may also have more general application in detecting morphologically complex structures of fluorescently labelled proteins present in clusters of other types of cells.
Universal rule for the symmetric division of plant cells
Besson, Sébastien; Dumais, Jacques
2011-01-01
The division of eukaryotic cells involves the assembly of complex cytoskeletal structures to exert the forces required for chromosome segregation and cytokinesis. In plants, empirical evidence suggests that tensional forces within the cytoskeleton cause cells to divide along the plane that minimizes the surface area of the cell plate (Errera’s rule) while creating daughter cells of equal size. However, exceptions to Errera’s rule cast doubt on whether a broadly applicable rule can be formulated for plant cell division. Here, we show that the selection of the plane of division involves a competition between alternative configurations whose geometries represent local area minima. We find that the probability of observing a particular division configuration increases inversely with its relative area according to an exponential probability distribution known as the Gibbs measure. Moreover, a comparison across land plants and their most recent algal ancestors confirms that the probability distribution is widely conserved and independent of cell shape and size. Using a maximum entropy formulation, we show that this empirical division rule is predicted by the dynamics of the tense cytoskeletal elements that lead to the positioning of the preprophase band. Based on the fact that the division plane is selected from the sole interaction of the cytoskeleton with cell shape, we posit that the new rule represents the default mechanism for plant cell division when internal or external cues are absent. PMID:21383128
Beemster, Gerrit T.S.; Baskin, Tobias I.
1998-01-01
To investigate the relation between cell division and expansion in the regulation of organ growth rate, we used Arabidopsis thaliana primary roots grown vertically at 20°C with an elongation rate that increased steadily during the first 14 d after germination. We measured spatial profiles of longitudinal velocity and cell length and calculated parameters of cell expansion and division, including rates of local cell production (cells mm−1 h−1) and cell division (cells cell−1 h−1). Data were obtained for the root cortex and also for the two types of epidermal cell, trichoblasts and atrichoblasts. Accelerating root elongation was caused by an increasingly longer growth zone, while maximal strain rates remained unchanged. The enlargement of the growth zone and, hence, the accelerating root elongation rate, were accompanied by a nearly proportionally increased cell production. This increased production was caused by increasingly numerous dividing cells, whereas their rates of division remained approximately constant. Additionally, the spatial profile of cell division rate was essentially constant. The meristem was longer than generally assumed, extending well into the region where cells elongated rapidly. In the two epidermal cell types, meristem length and cell division rate were both very similar to that of cortical cells, and differences in cell length between the two epidermal cell types originated at the apex of the meristem. These results highlight the importance of controlling the number of dividing cells, both to generate tissues with different cell lengths and to regulate the rate of organ enlargement. PMID:9536070
The distinctive cell division interactome of Neisseria gonorrhoeae.
Zou, Yinan; Li, Yan; Dillon, Jo-Anne R
2017-12-12
Bacterial cell division is an essential process driven by the formation of a Z-ring structure, as a cytoskeletal scaffold at the mid-cell, followed by the recruitment of various proteins which form the divisome. The cell division interactome reflects the complement of different interactions between all divisome proteins. To date, only two cell division interactomes have been characterized, in Escherichia coli and in Streptococcus pneumoniae. The cell divison proteins encoded by Neisseria gonorrhoeae include FtsZ, FtsA, ZipA, FtsK, FtsQ, FtsI, FtsW, and FtsN. The purpose of the present study was to characterize the cell division interactome of N. gonorrhoeae using several different methods to identify protein-protein interactions. We also characterized the specific subdomains of FtsA implicated in interactions with FtsZ, FtsQ, FtsN and FtsW. Using a combination of bacterial two-hybrid (B2H), glutathione S-transferase (GST) pull-down assays, and surface plasmon resonance (SPR), nine interactions were observed among the eight gonococcal cell division proteins tested. ZipA did not interact with any other cell division proteins. Comparisons of the N. gonorrhoeae cell division interactome with the published interactomes from E. coli and S. pneumoniae indicated that FtsA-FtsZ and FtsZ-FtsK interactions were common to all three species. FtsA-FtsW and FtsK-FtsN interactions were only present in N. gonorrhoeae. The 2A and 2B subdomains of FtsA Ng were involved in interactions with FtsQ, FtsZ, and FtsN, and the 2A subdomain was involved in interaction with FtsW. Results from this research indicate that N. gonorrhoeae has a distinctive cell division interactome as compared with other microorganisms.
Fenton, Andrew K; Gerdes, Kenn
2013-07-03
How bacteria coordinate cell growth with division is not well understood. Bacterial cell elongation is controlled by actin-MreB while cell division is governed by tubulin-FtsZ. A ring-like structure containing FtsZ (the Z ring) at mid-cell attracts other cell division proteins to form the divisome, an essential protein assembly required for septum synthesis and cell separation. The Z ring exists at mid-cell during a major part of the cell cycle without contracting. Here, we show that MreB and FtsZ of Escherichia coli interact directly and that this interaction is required for Z ring contraction. We further show that the MreB-FtsZ interaction is required for transfer of cell-wall biosynthetic enzymes from the lateral to the mature divisome, allowing cells to synthesise the septum. Our observations show that bacterial cell division is coupled to cell elongation via a direct and essential interaction between FtsZ and MreB.
Fenton, Andrew K; Gerdes, Kenn
2013-01-01
How bacteria coordinate cell growth with division is not well understood. Bacterial cell elongation is controlled by actin–MreB while cell division is governed by tubulin–FtsZ. A ring-like structure containing FtsZ (the Z ring) at mid-cell attracts other cell division proteins to form the divisome, an essential protein assembly required for septum synthesis and cell separation. The Z ring exists at mid-cell during a major part of the cell cycle without contracting. Here, we show that MreB and FtsZ of Escherichia coli interact directly and that this interaction is required for Z ring contraction. We further show that the MreB–FtsZ interaction is required for transfer of cell-wall biosynthetic enzymes from the lateral to the mature divisome, allowing cells to synthesise the septum. Our observations show that bacterial cell division is coupled to cell elongation via a direct and essential interaction between FtsZ and MreB. PMID:23756461
Kinetics of large-scale chromosomal movement during asymmetric cell division in Escherichia coli
Männik, Jaana; O’Neill, Jordan C.
2017-01-01
Coordination between cell division and chromosome replication is essential for a cell to produce viable progeny. In the commonly accepted view, Escherichia coli realize this coordination via the accurate positioning of its cell division apparatus relative to the nucleoids. However, E. coli lacking proper positioning of its cell division planes can still successfully propagate. Here, we characterize how these cells partition their chromosomes into daughters during such asymmetric divisions. Using quantitative time-lapse imaging, we show that DNA translocase, FtsK, can pump as much as 80% (3.7 Mb) of the chromosome between daughters at an average rate of 1700±800 bp/s. Pauses in DNA translocation are rare, and in no occasions did we observe reversals at experimental time scales of a few minutes. The majority of DNA movement occurs at the latest stages of cell division when the cell division protein ZipA has already dissociated from the septum, and the septum has closed to a narrow channel with a diameter much smaller than the resolution limit of the microscope (~250 nm). Our data suggest that the narrow constriction is necessary for effective translocation of DNA by FtsK. PMID:28234902
A Canadian perspective on anterior cervical discectomies: practice patterns and preferences
Bennardo, Michael; Farrokhyar, Forough; Martyniuk, Amanda; Reddy, Kesava
2018-01-01
Background The purpose of this study is to elucidate the current practice patterns of Canadian neurosurgeons with regards to anterior cervical discectomy (ACD). Methods A one-page questionnaire was sent out using SurveyMonkey to all neurosurgeon members of the Canadian Neurological Sciences Federation (CNSF). End points were surgeon preference for ACD surgical method, graft source, the length of collar usage and the recommended time before returning to work. Results Response rate was 74.0%. Of the responders, 75.0% performed single level ACD and 18.3% had completed spine fellowships. The majority (68.2%) chose ACD with fusion and plating (ACDFP) as their preferred method with allograft being the most popular choice of fusion material (44.3%). Most of the respondents did not prescribe collars (60.9%) and when they did, hard collar was prescribed most often (76.9%) and AspenTM collar was the most popular choice (67.7%). The majority of surgeons chose ‘other’ as their response for length of time for collar use (40.0%) while allowing them to take their collars off at night (78.1%). Most of the surgeons recommended physiotherapy post-operatively (58.1%) and time to physiotherapy was 6–8 weeks. Recommended back to work time was 6 weeks for 44.9% of respondents. In the cross analysis, surgeons who performed ACDF were more likely to prescribe collars (50%, P=0.01) versus surgeons who performed ACDFP (21.7%, P=0.01). Conclusions Our survey is an up to date description of current practice patterns for ACD amongst Canadian neurosurgeons. PMID:29732425
Perez, Claudio I; Chansangpetch, Sunee; Feinstein, Max; Mora, Marta; Nguyen, Anwell; Badr, Mai; Masis, Marisse; Lin, Shan C
2018-05-04
To evaluate a novel gonioscopy score as a potential predictor for intraocular pressure (IOP) reduction after cataract surgery. Prospective study that included consecutive patients with or without glaucoma, either with open or narrow angles but without peripheral anterior synechiae, who underwent phacoemulsification. Eyes with intraoperative complications and secondary glaucoma were excluded. A preoperative gonioscopy score was created, summing the Shaffer gonioscopy grading in 4 quadrants (range 0-16). To determine variables associated with IOP change at 6 months, univariate and multivariate linear mixed-effects regression analysis was performed adjusting for age, sex, and preoperative IOP. 188 eyes from 137 patients were enrolled. The mean age of the patients was 75.0 (±8.5) years and the average preoperative IOP was 15.6 (±3.6) mm Hg with 0.7 (range 0-4) glaucoma medications. The mean IOP reduction after phaco was 3.0 (±2.6) mm Hg at postoperative month 6. After multivariate analysis, preop IOP (β=0.49 [0.41 - 0.58] P<0.0001), gonioscopy score (β=-0.17 [-0.24 - -0.09] P<0.0001), ACD (β=-0.88 [-1.64 - -0.14] P=0.02) and IOP/ACD ratio (β=0.45 [0.07 - 0.83] P=0.021) were associated with IOP reduction at 6 months. Preoperative predictors for IOP reduction after cataract surgery were preoperative IOP, ACD, gonioscopy score and IOP/ACD ratio. The IOP/ACD ratio and gonioscopy score can be easy parameters to obtain and may help clinicians to estimate the IOP reduction after phaco.
Luft, Nikolaus; Hirnschall, Nino; Farrokhi, Sanaz; Findl, Oliver
2015-08-01
To assess whether anterior chamber depth (ACD) measurements in pseudophakic eyes obtained with partial coherence interferometry (PCI) and optical low-coherence reflectometry (OLCR) devices can be used interchangeably. Vienna Institute for Research in Ocular Surgery, A Karl Landsteiner Institute, Hanusch Hospital, Vienna, Austria. Prospective case series. The ACD measurements in 1 eye of each pseudophakic patient were performed with the PCI-based ACMaster device and the OLCR-based Lenstar LS900 device at least 1 day postoperatively. The study comprised 65 eyes of 65 patients with a mean age of 71.7 years ± 9.0 (SD) (range 39 to 91 years). In 15 eyes, no valid ACD readings could be obtained with the OLCR device. No obvious reason for these measurement failures was identified; however, tear-film alterations shortly after surgery were suspected. No significant difference in the mean ACD in the remaining 50 eyes was found between PCI measurements (5019 ± 660 μm; range 4008 to 6181 μm) and OLCR measurements (5015 ± 663 μm; range 4017 to 6163 μm) (P = .06). Three (6%) of 50 measurements were not within the 95% limits of agreement in the Bland-Altman analysis. Pseudophakic ACD measurements with the PCI and OLCR devices can be used interchangeably. The OLCR device proved to be more user-friendly and faster; however, in a substantial number of eyes, no usable values were obtainable. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Pietra, Stefano; Gustavsson, Anna; Kiefer, Christian; Kalmbach, Lothar; Hörstedt, Per; Ikeda, Yoshihisa; Stepanova, Anna N; Alonso, Jose M; Grebe, Markus
2013-01-01
The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes.
Ondracka, Andrej; Dudin, Omaya; Ruiz-Trillo, Iñaki
2018-06-18
Coordination of the cell division cycle with the growth of the cell is critical to achieve cell size homeostasis [1]. Mechanisms coupling the cell division cycle with cell growth have been described across diverse eukaryotic taxa [2-4], but little is known about how these processes are coordinated in organisms that undergo more complex life cycles, such as coenocytic growth. Coenocytes (multinucleate cells formed by sequential nuclear divisions without cytokinesis) are commonly found across the eukaryotic kingdom, including in animal and plant tissues and several lineages of unicellular eukaryotes [5]. Among the organisms that form coenocytes are ichthyosporeans, a lineage of unicellular holozoans that are of significant interest due to their phylogenetic placement as one of the closest relatives of animals [6]. Here, we characterize the coenocytic cell division cycle in the ichthyosporean Sphaeroforma arctica. We observe that, in laboratory conditions, S. arctica cells undergo a uniform and easily synchronizable coenocytic cell cycle, reaching up to 128 nuclei per cell before cellularization and release of daughter cells. Cycles of nuclear division occur synchronously within the coenocyte and in regular time intervals (11-12 hr). We find that the growth of cell volume is dependent on concentration of nutrients in the media; in contrast, the rate of nuclear division cycles is constant over a range of nutrient concentrations. Together, the results suggest that nuclear division cycles in the coenocytic growth of S. arctica are driven by a timer, which ensures periodic and synchronous nuclear cycles independent of the cell size and growth. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-06
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), CDC announces the following meeting of the aforementioned committee. Time and date: 8:30 a.m.-2:30 p.m., October 27, 2011. Place: CDC...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-27
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section... Prevention (CDC) announces the following meeting of the aforementioned committee. Time and Date: 8:30 a.m.-3:00 p.m. (EDT), April 25, 2013. Place: CDC, Building 21, Rooms 1204 A/B, 1600 Clifton Road, NE...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Grula, E.A.; Grula, M.M.
Inhibition of cell division in an Erwinia sp. occurs in the presence of any of six D-amino acids, penicillin, or ultraviolet light. Cell-division inhibition caused by D-amino acids is pH-dependent; however, elongation caused by penicillin occurs over a wide range of pH. Bulging and spheroplast formation in the presence of penicillin occurs only at pH values below 7.6; however, division continues to be inhibited at higher pH levels. Reversal of cell-division inhibition caused by two D-amino acids (phenylalanine and histidine) can be partially overcome by their respective L-isomers. Divalent cations (Zn, Ca, Mn) cause varying amounts of reversal of divisionmore » inhibition in all systems studied; each system appears to have an individual requirement. All induced division inhibitions, including that caused by penicillin, can be reversed by pantoyl lactone or omega methylpantoyl lactone. Evidence is presented and discussed concerning the possible importance of pantoyl lactone and divalent cations in terminal steps of the cell-division process in this organism. (auth)« less
Hand dermatitis in auto mechanics and machinists.
Donovan, Jeffrey C H; Kudla, Irena; Holness, D Linn
2007-09-01
Auto mechanics and machinists presenting with suspected allergic contact dermatitis (ACD) have traditionally been patch-tested with a standard screening tray and a specialty tray such as the Oil and Cooling Fluid Series. While this has proven useful for patch-testing the machinist, there is a need for the development of a more specific allergen testing tray for the auto mechanic. The objective of the study was to compare clinical features and patch-test results of auto mechanics and machinists with hand dermatitis to evaluate differences in allergen profiles. We performed a chart review of 33 auto mechanics and 24 machinists referred to our Occupational Contact Dermatitis Clinic from 2002 to 2005 for evaluation of hand dermatitis. With a panel of 84 allergens, 52 positive reactions were detected in 17 cases of ACD in mechanics. The profiles were different from the cases of ACD diagnosed in 10 of 24 machinists. Mechanics and machinists differ in the spectrum of occupational exposures. Patch testing with greater numbers of allergens likely identifies a larger proportion of mechanics with occupationally relevant ACD. Further study is needed to determine the most appropriate allergens to include in a clinically useful "mechanic's tray."
Forte, Giovanni; Petrucci, Francesco; Bocca, Beatrice
2008-09-01
Metal-induced allergic contact dermatitis (ACD) is expressed in a wide range of cutaneous reactions following dermal and systemic exposure to products such as cosmetics and tattoos, detergents, jewellery and piercing, leather tanning, articular prostheses and dental implants. Apart from the well known significance of nickel in developing ACD, other metals such as aluminium, beryllium, chromium, cobalt, copper, gold, iridium, mercury, palladium, platinum, rhodium and titanium represented emerging causes of skin hypersensitivity. Despite the European Union directives that limit the total nickel content in jewellery alloys, the water soluble chromium (VI) in cement, and metals banned in cosmetics, the diffusion of metal-induced ACD remained quite high. On this basis, a review on the epidemiology of metal allergens, the types of exposure, the skin penetration, the immune response, and the protein interaction is motivated. Moreover, in vivo and in vitro tests for the identification and potency of skin-sensitizing metals are here reviewed in a risk assessment framework for the protection of consumer's health. Avenues for ACD prevention and therapy such as observance of maximum allowable metal levels, optimization of metallurgic characteristics, efficacy of chelating agents and personal protection are also discussed.
Armstrong, Elizabeth M; Ciccone, Natalie; Hersh, Deborah; Katzenellebogen, Judith; Coffin, Juli; Thompson, Sandra; Flicker, Leon; Hayward, Colleen; Woods, Deborah; McAllister, Meaghan
2017-06-01
Acquired communication disorders (ACD), following stroke and traumatic brain injury, may not be correctly identified in Aboriginal Australians due to a lack of linguistically and culturally appropriate assessment tools. Within this paper we explore key issues that were considered in the development of the Aboriginal Communication Assessment After Brain Injury (ACAABI) - a screening tool designed to assess the presence of ACD in Aboriginal populations. A literature review and consultation with key stakeholders were undertaken to explore directions needed to develop a new tool, based on existing tools and recommendations for future developments. The literature searches revealed no existing screening tool for ACD in these populations, but identified tools in the areas of cognition and social-emotional wellbeing. Articles retrieved described details of the content and style of these tools, with recommendations for the development and administration of a new tool. The findings from the interview and focus group views were consistent with the approach recommended in the literature. There is a need for a screening tool for ACD to be developed but any tool must be informed by knowledge of Aboriginal language, culture and community input in order to be acceptable and valid.
Landsat-7 Simulation and Testing Environments
NASA Technical Reports Server (NTRS)
Holmes, E.; Ha, K.; Hawkins, K.; Lombardo, J.; Ram, M.; Sabelhaus, P.; Scott, S.; Phillips, R.
1999-01-01
A spacecraft Attitude Control and Determination Subsystem (ACDS) is heavily dependent upon simulation throughout its entire development, implementation and ground test cycle. Engineering simulation tools are typically developed to design and analyze control systems to validate the design and software simulation tools are required to qualify the flight software. However, the need for simulation does not end here. Operating the ACDS of a spacecraft on the ground requires the simulation of spacecraft dynamics, disturbance modeling and celestial body motion. Sensor data must also be simulated and substituted for actual sensor data on the ground so that the spacecraft will respond by sending commands to the actuators as they will on orbit. And finally, the simulators is the primary training tool and test-bed for the Flight Operations Team. In this paper various ACDS simulation, developed for or used by the Landsat 7 project will be described. The paper will include a description of each tool, its unique attributes, and its role in the overall development and testing of the ACDS. Finally, a section is included which discusses how the coordinated use of these simulation tools can maximize the probability of uncovering software, hardware and operations errors during the ground test process.
Grinenko, Tatyana; Eugster, Anne; Thielecke, Lars; Ramasz, Beáta; Krüger, Anja; Dietz, Sevina; Glauche, Ingmar; Gerbaulet, Alexander; von Bonin, Malte; Basak, Onur; Clevers, Hans; Chavakis, Triantafyllos; Wielockx, Ben
2018-05-15
Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67 RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle. Additionally, the phenotype of the undivided but differentiated progenitors correlated with the expression of lineage-specific genes and loss of multipotency. Thus HSC fate decisions can be uncoupled from physical cell division. These results facilitate a better understanding of the mechanisms that control fate decisions in hematopoietic cells.
Kvitko, O V; Koneva, I I; Sheiko, Y I; Anisovich, M V
2005-12-01
The causes of the indefinite propagation of immortalized cell populations remain insufficiently understood, that hinders the research of such fundamental processes as ageing and cancer. In this study the interrelations between clonal proliferation and abnormalities of mitotic divisions in the immortalized cell line established from the mouse embryo were investigated with the aid of computerized microscopy of living cells. 3 mitoses with three daughter cells and 7 asymmetric mitoses which generated two daughter cells of conspicuously different sizes were registered among 71 mitotic divisions in the individual cell genealogy. Abnormal mitotic divisions either did not slow the proliferation in cell clones compared with progenies of cells that divided by means of normal mitoses or were followed by the acceleration of divisions in consecutive cell generations. These data suggest that abnormal mitotic divisions may contribute to the maintenance of the immortalized state of cell populations by means of generating chromosomal instability.
Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging) of Escherichia coli
Clark, Michelle W.; Yie, Anna M.; Eder, Elizabeth K.; Dennis, Richard G.; Basting, Preston J.; Martinez, Keith A.; Jones, Brian D.; Slonczewski, Joan L.
2015-01-01
Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH), no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5) the cells maintained cytoplasmic pH values at 7.2–7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress. PMID:26713733
Höfflin, Felix; Jack, Alexander; Riedel, Christian; Mack-Bucher, Julia; Roos, Johannes; Corcelli, Corinna; Schultz, Christian; Wahle, Petra; Engelhardt, Maren
2017-01-01
The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type. PMID:29170630
Yabe, Taijiro; Ge, Xiaoyan; Pelegri, Francisco
2007-12-01
A female-sterile zebrafish maternal-effect mutation in cellular atoll (cea) results in defects in the initiation of cell division starting at the second cell division cycle. This phenomenon is caused by defects in centrosome duplication, which in turn affect the formation of a bipolar spindle. We show that cea encodes the centriolar coiled-coil protein Sas-6, and that zebrafish Cea/Sas-6 protein localizes to centrosomes. cea also has a genetic paternal contribution, which when mutated results in an arrested first cell division followed by normal cleavage. Our data supports the idea that, in zebrafish, paternally inherited centrosomes are required for the first cell division while maternally derived factors are required for centrosomal duplication and cell divisions in subsequent cell cycles. DNA synthesis ensues in the absence of centrosome duplication, and the one-cycle delay in the first cell division caused by cea mutant sperm leads to whole genome duplication. We discuss the potential implications of these findings with regards to the origin of polyploidization in animal species. In addition, the uncoupling of developmental time and cell division count caused by the cea mutation suggests the presence of a time window, normally corresponding to the first two cell cycles, which is permissive for germ plasm recruitment.
Using stochastic cell division and death to probe minimal units of cellular replication
NASA Astrophysics Data System (ADS)
Chib, Savita; Das, Suman; Venkatesan, Soumya; Sai Narain Seshasayee, Aswin; Thattai, Mukund
2018-03-01
The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in Escherichia coli populations treated with a ribosome-targeting antibiotic. We find that the growth exponent from macroscopic cell growth or decay measurements can be represented as the difference of microscopic first-order cell division and death rates. The boundary between cell growth and decay, at which the number of live cells remains constant over time, occurs at the minimal inhibitory concentration (MIC) of the antibiotic. This state appears macroscopically static but is microscopically dynamic: division and death rates exactly cancel at MIC but each is remarkably high, reaching 60% of the antibiotic-free division rate. A stochastic model of cells as collections of minimal replicating units we term ‘widgets’ reproduces both steady-state and transient features of our experiments. Sub-cellular fluctuations of widget numbers stochastically drive each new daughter cell to one of two alternate fates, division or death. First-order division or death rates emerge as eigenvalues of a stationary Markov process, and can be expressed in terms of the widget’s molecular properties. High division and death rates at MIC arise due to low mean and high relative fluctuations of widget number. Isolating cells at the threshold of irreversible death might allow molecular characterization of this minimal replication unit.
RanGAP1 is a continuous marker of the Arabidopsis cell division plane
Xu, Xianfeng Morgan; Zhao, Qiao; Rodrigo-Peiris, Thushani; Brkljacic, Jelena; He, Chao Sylvia; Müller, Sabine; Meier, Iris
2008-01-01
In higher plants, the plane of cell division is faithfully predicted by the preprophase band (PPB). The PPB, a cortical ring of microtubules and F-actin, disassembles upon nuclear-envelope breakdown. During cytokinesis, the expanding cell plate fuses with the plasma membrane at the cortical division site, the site of the former PPB. The nature of the “molecular memory” that is left behind by the PPB and is proposed to guide the cell plate to the cortical division site is unknown. RanGAP is the GTPase activating protein of the small GTPase Ran, which provides spatial information for nucleocytoplasmic transport and various mitotic processes in animals. Here, we show that, in dividing root cells, Arabidopsis RanGAP1 concentrates at the PPB and remains associated with the cortical division site during mitosis and cytokinesis, requiring its N-terminal targeting domain. In a fass/ton2 mutant, which affects PPB formation, RanGAP1 recruitment to the PPB site is lost, while its PPB retention is microtubule-independent. RanGAP1 persistence at the cortical division site, but not its initial accumulation at the PPB requires the 2 cytokinesis-regulating kinesins POK1 and POK2. Depletion of RanGAP by inducible RNAi leads to oblique cell walls and cell-wall stubs in root cell files, consistent with cytokinesis defects. We propose that Arabidopsis RanGAP, a continuous positive protein marker of the plant division plane, has a role in spatial signaling during plant cell division. PMID:19011093
Cell division and endoreduplication: doubtful engines of vegetative growth.
John, Peter C L; Qi, Ruhu
2008-03-01
Currently, there is little information to indicate whether plant cell division and development is the collective effect of individual cell programming (cell-based) or is determined by organ-wide growth (organismal). Modulation of cell division does not confirm cell autonomous programming of cell expansion; instead, final cell size seems to be determined by the balance between cells formed and subsequent tissue growth. Control of growth in regions of the plant therefore has great importance in determining cell, organ and plant development. Here, we question the view that formation of new cells and their programmed expansion is the driving force of growth. We believe there is evidence that division does not drive, but requires, cell growth and a similar requirement for growth is detected in the modified cycle termed endoreduplication.
Dynamic self-organisation of haematopoiesis and (a)symmetric cell division.
Måløy, Marthe; Måløy, Frode; Jakobsen, Per; Olav Brandsdal, Bjørn
2017-02-07
A model of haematopoiesis that links self-organisation with symmetric and asymmetric cell division is presented in this paper. It is assumed that all cell divisions are completely random events, and that the daughter cells resulting from symmetric and asymmetric stem cell divisions are, in general, phenotypically identical, and still, the haematopoietic system has the flexibility to self-renew, produce mature cells by differentiation, and regenerate undifferentiated and differentiated cells when necessary, due to self-organisation. As far as we know, no previous model implements symmetric and asymmetric division as the result of self-organisation. The model presented in this paper is inspired by experiments on the Drosophila germline stem cell, which imply that under normal conditions, the stem cells typically divide asymmetrically, whereas during regeneration, the rate of symmetric division increases. Moreover, the model can reproduce several of the results from experiments on female Safari cats. In particular, the model can explain why significant fluctuation in the phenotypes of haematopoietic cells was observed in some cats, when the haematopoietic system had reached normal population level after regeneration. To our knowledge, no previous model of haematopoiesis in Safari cats has captured this phenomenon. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
FitzGerald, Paul F.; Butts, Matthew D.; Roberts, Jeannette C.; Colborn, Robert E.; Torres, Andrew S.; Lee, Brian D.; Yeh, Benjamin M.; Bonitatibus, Peter J.
2016-01-01
Objectives To produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ) coated soluble tantalum oxide nanoparticles (CZ-TaO NPs). We chose tantalum to provide superior imaging performance compared to current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. The aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared to clinically-used iodinated agents. Materials and Methods We evaluated CT imaging performance of our CZ-TaO NPs compared to an iodinated agent in live rats, imaged centrally-located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats’ great vessels at high temporal resolution during and following contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. CZ-TaO NPs were synthesized and analyzed in detail. We used multi-dimensional nuclear magnetic resonance (NMR) to determine surface functionality of the nanoparticles. We measured nanoparticle size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Results CT imaging studies demonstrated image contrast improvement of approximately 40–50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects following injection in healthy naïve rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week following injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin (NGAL) biomarker was measured at 24 and 48 hours. Compared to other tantalum oxide nanoparticles reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations >200 mg Ta/mL, and were similar in these physical properties to dimeric iodine-based contrast agents. Conclusions We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically-viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared to current iodinated agents. PMID:27115702
FitzGerald, Paul F; Butts, Matthew D; Roberts, Jeannette C; Colborn, Robert E; Torres, Andrew S; Lee, Brian D; Yeh, Benjamin M; Bonitatibus, Peter J
2016-12-01
The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.
FRET detection of lymphocyte function–associated antigen-1 conformational extension
Chigaev, Alexandre; Smagley, Yelena; Haynes, Mark K.; Ursu, Oleg; Bologa, Cristian G.; Halip, Liliana; Oprea, Tudor; Waller, Anna; Carter, Mark B.; Zhang, Yinan; Wang, Wei; Buranda, Tione; Sklar, Larry A.
2015-01-01
Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1–specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation. PMID:25378583
The Effect of Dihydroxyacetone on the Liquid Storage Properties of Human Blood.
Addition of dihydroxyacetone (DHA) to acid-citrate-phosphate (ACD) blood is effective in partially maintaining 2,3- diphosphoglycerate levels for a...period of 21 to 28 days. DHA has no effect on adenosine triphosphate (ATP) levels or cell viability. The overall effect of adenine with DHA is...unfavorable since it retards the effect of the DHA while only slightly raising ATP levels . DHA may be valuable in maintaining increased hemoglobin function levels throughout the present 21 day storage period. (Author)
Increasing the Energy Efficiency of Aluminum-Reduction Cells Using Modified Cathodes
NASA Astrophysics Data System (ADS)
Jianping, Peng; Yang, Song; Yuezhong, Di; Yaowu, Wang; Naixiang, Feng
2017-10-01
A cathode with an inclined surface (5°) and increased bar collector height (230 mm high) was incorporated into two 300-kA industrial aluminum-reduction cells. The voltage of the cells with the modified cathode was reduced by approximately 200 mV when compared with that of a conventional cell with a flat cathode. Through the use of simulations, the reduction in the cell voltage was attributed to the cathode modification (40 mV) and a reduced electrolyte level of 0.5 cm (160 mV). As a result of reduced anode cathode distance (ACD), the ledge toe was extended to the anode shadow by 12 cm. This caused a large inverted horizontal current and a velocity increase. The ledge profile returned to the desired position when the cells were insulated more effectively, and the metal velocity and metal crest in the modified cells were reduced accordingly.
Estimating division and death rates from CFSE data
NASA Astrophysics Data System (ADS)
de Boer, Rob J.; Perelson, Alan S.
2005-12-01
The division tracking dye, carboxyfluorescin diacetate succinimidyl ester (CFSE) is currently the most informative labeling technique for characterizing the division history of cells in the immune system. Gett and Hodgkin (Nat. Immunol. 1 (2000) 239-244) have proposed to normalize CFSE data by the 2-fold expansion that is associated with each division, and have argued that the mean of the normalized data increases linearly with time, t, with a slope reflecting the division rate p. We develop a number of mathematical models for the clonal expansion of quiescent cells after stimulation and show, within the context of these models, under which conditions this approach is valid. We compare three means of the distribution of cells over the CFSE profile at time t: the mean, [mu](t), the mean of the normalized distribution, [mu]2(t), and the mean of the normalized distribution excluding nondivided cells, .In the simplest models, which deal with homogeneous populations of cells with constant division and death rates, the normalized frequency distribution of the cells over the respective division numbers is a Poisson distribution with mean [mu]2(t)=pt, where p is the division rate. The fact that in the data these distributions seem Gaussian is therefore insufficient to establish that the times at which cells are recruited into the first division have a Gaussian variation because the Poisson distribution approaches the Gaussian distribution for large pt. Excluding nondivided cells complicates the data analysis because , and only approaches a slope p after an initial transient.In models where the first division of the quiescent cells takes longer than later divisions, all three means have an initial transient before they approach an asymptotic regime, which is the expected [mu](t)=2pt and . Such a transient markedly complicates the data analysis. After the same initial transients, the normalized cell numbers tend to decrease at a rate e-dt, where d is the death rate.Nonlinear parameter fitting of CFSE data obtained from Gett and Hodgkin to ordinary differential equation (ODE) models with first-order terms for cell proliferation and death gave poor fits to the data. The Smith-Martin model with an explicit time delay for the deterministic phase of the cell cycle performed much better. Nevertheless, the insights gained from analysis of the ODEs proved useful as we showed by generating virtual CFSE data with a simulation model, where cell cycle times were drawn from various distributions, and then computing the various mean division numbers.
Droplet size influences division of mammalian cell factories in droplet microfluidic cultivation.
Periyannan Rajeswari, Prem Kumar; Joensson, Haakan N; Andersson-Svahn, Helene
2017-01-01
The potential of using droplet microfluidics for screening mammalian cell factories has been limited by the difficulty in achieving continuous cell division during cultivation in droplets. Here, we report the influence of droplet size on mammalian cell division and viability during cultivation in droplets. Chinese Hamster Ovary (CHO) cells, the most widely used mammalian host cells for biopharmaceuticals production were encapsulated and cultivated in 33, 180 and 320 pL droplets for 3 days. Periodic monitoring of the droplets during incubation showed that the cell divisions in 33 pL droplets stopped after 24 h, whereas continuous cell division was observed in 180 and 320 pL droplets for 72 h. The viability of the cells cultivated in the 33 pL droplets also dropped to about 50% in 72 h. In contrast, the viability of the cells in the larger droplets was above 90% even after 72 h of cultivation, making them a more suitable droplet size for 72-h cultivation. This study shows a direct correlation of microfluidic droplet size to the division and viability of mammalian cells. This highlights the importance of selecting suitable droplet size for mammalian cell factory screening assays. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-06
...: Leandris Liburd, Ph.D., M.P.H., M.A., Designated Federal Officer, HDS, ACD, CDC, 1600 Clifton Road, NE...), CDC announces the following meeting of the aforementioned subcommittee: Time and Date: 9 a.m.-4 p.m... comment period, which is tentatively scheduled from 3:30 p.m. to 4 p.m. This meeting is also available by...
Setälä, Piritta Anniina; Virkkunen, Ilkka Tapani; Kämäräinen, Antti Jaakko; Huhtala, Heini Sisko Annamari; Virta, Janne Severi; Yli-Hankala, Arvi Mikael; Hoppu, Sanna Elisa
2018-05-16
Active compression-decompression (ACD) devices have enhanced end-tidal carbon dioxide (ETCO 2 ) output in experimental cardiopulmonary resuscitation (CPR) studies. However, the results in out-of-hospital cardiac arrest (OHCA) patients have shown inconsistent outcomes, and earlier studies lacked quality control of CPR attempts. We compared manual CPR with ACD-CPR by measuring ETCO 2 output using an audiovisual feedback defibrillator to ensure continuous high quality resuscitation attempts. 10 witnessed OHCAs were resuscitated, rotating a 2 min cycle with manual CPR and a 2 min cycle of ACD-CPR. Patients were intubated and the ventilation rate was held constant during CPR. CPR quality parameters and ETCO 2 values were collected continuously with the defibrillator. Differences in ETCO 2 output between manual CPR and ACD-CPR were analysed using a linear mixed model where ETCO 2 output produced by a summary of the 2 min cycles was included as the dependent variable, the patient as a random factor and method as a fixed effect. These comparisons were made within each OHCA case to minimise confounding factors between the cases. Mean length of the CPR episodes was 37 (SD 8) min. Mean compression depth was 76 (SD 1.3) mm versus 71 (SD1.0) mm, and mean compression rate was 100 per min (SD 6.7) versus 105 per min (SD 4.9) between ACD-CPR and manual CPR, respectively. For ETCO 2 output, the interaction between the method and the patient was significant (P<0.001). ETCO 2 output was higher with manual CPR in 6 of the 10 cases. This study suggests that quality controlled ACD-CPR is not superior to quality controlled manual CPR when ETCO 2 is used as a quantitative measure of CPR effectiveness. NCT00951704; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
The biometric study in different stages of primary angle-closure glaucoma
Chen, Y-Y; Chen, Y-Y; Sheu, S-J; Chou, P
2013-01-01
Purpose This study compared the general and ocular biometric characteristics of normal, primary angle closure (PAC), and primary angle-closure glaucoma (PACG) patients to better understand the possible relationship between differences in ocular parameters that might predict risk for PACG in PAC patients. Methods One hundred normal, 90 PAC, and 90 PACG eyes were retrospectively reviewed. General characteristics such as age, gender, body height, body weight, blood pressure, pulse, systemic diseases, and education level were recorded. Ocular findings included visual acuity, intraocular pressure, refraction, cup to disc ratio, and ocular biometry. Ocular biometry was obtained by A-scan ultrasonography (Digital A/B scan 5500; Sonomed Inc., Lake Success, NY, USA). The parameters recorded were anterior chamber depth (ACD), lens thickness (LT), axial length (AXL), lens/axial length factor (LAF), and relative lens position (RLP). Results Although the controls, PAC group, and PACG group were found to be significantly different in age (62.7±9.8; 65.3±7.5; and 66.0±7.4, respectively), there were no gender differences. With regard to ocular parameters, the ACD tended to decrease and the LT and LAF tended to increase from normal to PAC to PACG. The eyes of the PACG group had significantly shallower ACD (P<0.001) and thicker lens (P<0.001) than those of the PAC group. While PAC had similar lens position to the control group, PACG had more anteriorly positioned lens than the PAC group (P<0.001). Logistic regression analysis found a significant association between a decrease in ACD and increased risk of PACG (odds ratio (OR)=3.59 for 0.2 mm decrease in ACD) as well as a significant association between an increase in LT and increased risk of PACG (OR=1.30). Conclusions In addition to LT, a shallower ACD owing to a change in RLP may have a role in the progression from PAC to PACG. Owing to the differences of certain biometric characteristics between PAC and PACG, A-scan ultrasonography might potentially be used for the early detection of PACG in PAC eyes. PMID:23788204
Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness.
Cerulus, Bram; New, Aaron M; Pougach, Ksenia; Verstrepen, Kevin J
2016-05-09
The fitness effect of biological noise remains unclear. For example, even within clonal microbial populations, individual cells grow at different speeds. Although it is known that the individuals' mean growth speed can affect population-level fitness, it is unclear how or whether growth speed heterogeneity itself is subject to natural selection. Here, we show that noisy single-cell division times can significantly affect population-level growth rate. Using time-lapse microscopy to measure the division times of thousands of individual S. cerevisiae cells across different genetic and environmental backgrounds, we find that the length of individual cells' division times can vary substantially between clonal individuals and that sublineages often show epigenetic inheritance of division times. By combining these experimental measurements with mathematical modeling, we find that, for a given mean division time, increasing heterogeneity and epigenetic inheritance of division times increases the population growth rate. Furthermore, we demonstrate that the heterogeneity and epigenetic inheritance of single-cell division times can be linked with variation in the expression of catabolic genes. Taken together, our results reveal how a change in noisy single-cell behaviors can directly influence fitness through dynamics that operate independently of effects caused by changes to the mean. These results not only allow a better understanding of microbial fitness but also help to more accurately predict fitness in other clonal populations, such as tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.
The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions.
Singhvi, Aakanksha; Teuliere, Jerome; Talavera, Karla; Cordes, Shaun; Ou, Guangshuo; Vale, Ronald D; Prasad, Brinda C; Clark, Scott G; Garriga, Gian
2011-06-07
During development, all cells make the decision to live or die. Although the molecular mechanisms that execute the apoptotic program are well defined, less is known about how cells decide whether to live or die. In C. elegans, this decision is linked to how cells divide asymmetrically [1, 2]. Several classes of molecules are known to regulate asymmetric cell divisions in metazoans, yet these molecules do not appear to control C. elegans divisions that produce apoptotic cells [3]. We identified CNT-2, an Arf GTPase-activating protein (GAP) of the AGAP family, as a novel regulator of this type of neuroblast division. Loss of CNT-2 alters daughter cell size and causes the apoptotic cell to adopt the fate of its sister cell, resulting in extra neurons. CNT-2's Arf GAP activity is essential for its function in these divisions. The N terminus of CNT-2, which contains a GTPase-like domain that defines the AGAP class of Arf GAPs, negatively regulates CNT-2's function. We provide evidence that CNT-2 regulates receptor-mediated endocytosis and consider the implications of its role in asymmetric cell divisions. Copyright © 2011 Elsevier Ltd. All rights reserved.
Characterization of dependencies between growth and division in budding yeast
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mayhew, Michael B.; Iversen, Edwin S.; Hartemink, Alexander J.
Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination or ‘size control’ appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G 2/M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G1. Moreover, in unicellular organisms, coordination betweenmore » growth and division has commonly been analyzed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyze both intra- and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (1) that S/G 2/M durations are systematically longer in daughters than in mothers, (2) of dependencies between S/G2/M and size at budding that echo the classical G1 dependencies, and, (3) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modelers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes.« less
Characterization of dependencies between growth and division in budding yeast
Mayhew, Michael B.; Iversen, Edwin S.; Hartemink, Alexander J.
2017-02-01
Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination or ‘size control’ appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G 2/M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G1. Moreover, in unicellular organisms, coordination betweenmore » growth and division has commonly been analyzed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyze both intra- and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (1) that S/G 2/M durations are systematically longer in daughters than in mothers, (2) of dependencies between S/G2/M and size at budding that echo the classical G1 dependencies, and, (3) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modelers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes.« less
Characterization of dependencies between growth and division in budding yeast
Iversen, Edwin S.; Hartemink, Alexander J.
2017-01-01
Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination or ‘size control’ appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G2/M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G1. Moreover, in unicellular organisms, coordination between growth and division has commonly been analysed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyse both intra- and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (i) that S/G2/M durations are systematically longer in daughters than in mothers, (ii) of dependencies between S/G2/M and size at budding that echo the classical G1 dependencies, and (iii) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modellers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes. PMID:28228543
Characterization of dependencies between growth and division in budding yeast.
Mayhew, Michael B; Iversen, Edwin S; Hartemink, Alexander J
2017-02-01
Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae , this coordination or 'size control' appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G 1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G 2 /M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G 1 Moreover, in unicellular organisms, coordination between growth and division has commonly been analysed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyse both intra- and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (i) that S/G 2 /M durations are systematically longer in daughters than in mothers, (ii) of dependencies between S/G 2 /M and size at budding that echo the classical G 1 dependencies, and (iii) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modellers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes. © 2017 The Author(s).
LocZ Is a New Cell Division Protein Involved in Proper Septum Placement in Streptococcus pneumoniae
Holečková, Nela; Molle, Virginie; Buriánková, Karolína; Benada, Oldřich; Kofroňová, Olga; Ulrych, Aleš; Branny, Pavel
2014-01-01
ABSTRACT How bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement in Streptococcus pneumoniae. We show that locZ is not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division. PMID:25550321
Pietra, Stefano; Gustavsson, Anna; Kiefer, Christian; Kalmbach, Lothar; Hörstedt, Per; Ikeda, Yoshihisa; Stepanova, Anna N.; Alonso, Jose M.; Grebe, Markus
2013-01-01
The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes. PMID:24240534
Asymmetric cell division requires specific mechanisms for adjusting global transcription.
Mena, Adriana; Medina, Daniel A; García-Martínez, José; Begley, Victoria; Singh, Abhyudai; Chávez, Sebastián; Muñoz-Centeno, Mari C; Pérez-Ortín, José E
2017-12-01
Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actual mRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller daughter cells. We show here that, contrarily to other eukaryotes with symmetric division, budding yeast keeps the nascent transcription rates of its RNA polymerases constant and increases mRNA stability. This control on RNA pol II-dependent transcription rate is obtained by controlling the cellular concentration of this enzyme. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Shoji, Jun; Inada, Noriko; Sawa, Mitsuru
2009-12-01
The objective of this study is to evaluate the practical usefulness of a scoring system using the 5-5-5 exacerbation grading scale for allergic conjunctivitis disease (ACD). Subjects were 103 patients with ACD including 40 patients with vernal keratoconjunctivitis (VKC), 20 patients with atopic keratoconjunctivitis (AKC), and 43 patients with allergic conjunctivitis (AC). The 5-5-5 exacerbation grading scale consists of the following 3 graded groups of clinical observations: the 100-point-grade group (100 points for each observation) includes active giant papillae, gelatinous infiltrates of the limbus, exfoliative epithelial keratopathy, shield ulcer and papillary proliferation at lower palpebral conjunctiva; the 10-point-grade group (10 points for each observation) includes blepharitis, papillary proliferation with velvety appearance, Horner-Trantas spots, edema of bulbal conjunctiva, and superficial punctate keratopathy; and the 1-point-grade group (1 point for each observation) includes papillae at upper palpebral conjunctiva, follicular lesion at lower palpebral conjunctiva, hyperemia of palpebral conjunctiva, hyperemia of bulbal conjunctiva, and lacrimal effusion. The total points in each grade group were determined as the severity score of the 5-5-5 exacerbation grading scale. The median severity scores of the 5-5-5 exacerbation grading scale in VKC, AKC and AC were 243 (range: 12-444), 32.5 (11-344), and 13 (2-33), respectively. The severity score of each ACD disease type was significantly different (P < 0.001, Kruskal-Wallis test). The severity of each type of ACD was classified as severe, moderate, or mild according to the severity score. The 5-5-5 exacerbation grading scale is a useful clinical tool for grading the severity of each type of ACD.
Preparing Adolescents With Chronic Disease for Transition to Adult Care: A Technology Program
Terrones, Laura; Tompane, Trevor; Dillon, Lindsay; Pian, Mark; Gottschalk, Michael; Norman, Gregory J.; Bartholomew, L. Kay
2014-01-01
BACKGROUND: Adolescents with chronic disease (ACD) must develop independent disease self-management and learn to communicate effectively with their health care team to transition from pediatric to adult-oriented health care systems. Disease-specific interventions have been implemented to aid specific ACD groups through transition. A generic approach might be effective and cost-saving. METHODS: Eighty-one ACD, aged 12 to 20 years, were recruited for a randomized clinical trial evaluating an 8-month transition intervention (MD2Me). MD2Me recipients received a 2-month intensive Web-based and text-delivered disease management and skill-based intervention followed by a 6-month review period. MD2Me recipients also had access to a texting algorithm for disease assessment and health care team contact. The intervention was applicable to adolescents with diverse chronic illnesses. Controls received mailed materials on general health topics. Disease management, health-related self-efficacy, and health assessments were performed at baseline and at 2 and 8 months. Frequency of patient-initiated communications was recorded over the study period. Outcomes were analyzed according to assigned treatment group over time. RESULTS: MD2Me recipients demonstrated significant improvements in performance of disease management tasks, health-related self-efficacy, and patient-initiated communications compared with controls. CONCLUSIONS: Outcomes in ACD improved significantly among recipients of a generic, technology-based intervention. Technology can deliver transition interventions to adolescents with diverse chronic illnesses, and a generic approach offers a cost-effective means of positively influencing transition outcomes. Further research is needed to determine whether improved short-term outcomes translate into an improved transition for ACD. PMID:24843066
AHAPS-functionalized silica nanoparticles do not modulate allergic contact dermatitis in mice
NASA Astrophysics Data System (ADS)
Ostrowski, Anja; Nordmeyer, Daniel; Mundhenk, Lars; Fluhr, Joachim W.; Lademann, Jürgen; Graf, Christina; Rühl, Eckart; Gruber, Achim D.
2014-09-01
Allergic contact dermatitis (ACD) is a common skin disease in people and may become a potential site of exposure to nanoparticles (NP). Silica nanoparticles (SiO2-NP) possess a promising potential for various medical and non-medical applications, including normal and diseased skin as target organs. However, it has been shown that negatively charged SiO2-NP may act as proinflammatory adjuvant in allergic diseases. The effect of topical SiO2-NP exposure on preexisting ACD has not been studied to date although this reflects a common in vivo situation. Of particular interest are the potential effects of positively charged N-(6-aminohexyl)-aminopropyltrimethoxysilane (AHAPS)-functionalized SiO2-NP which are promising candidates for delivery systems, including gene delivery into the skin. Here, the effects of such AHAPS-functionalized SiO2-NP (55 ± 6 nm in diameter) were studied in an oxazolone-induced ACD model in SKH1 mice and compared to ACD mice treated with vehicle only. The clinical course of the disease was assessed by monitoring of the transepidermal water loss (TEWL) and the erythema. In histologic and morphometric analyses, the distribution of particles, the degree of inflammation, epidermal thickness, and the inflammatory infiltrate were characterized and quantified by standard and special histological stains as well as immunohistochemistry for CD3+ lymphocytes. To assess possible systemic effects, serum immunoglobulin E (IgE) was determined by enzyme-linked immunosorbent assay. Following administration of AHAPS-SiO2-NP for five consecutive days, no effects were observed in all clinical, histologic, morphometric, and molecular parameters investigated. In conclusion, positively charged AHAPS-SiO2-NP seem not to affect the course of ACD during exposure for 5 days.
PREFACE: 12th European Workshop on Advanced Control and Diagnosis (ACD 2015)
NASA Astrophysics Data System (ADS)
Straka, Ondřej; Punčochář, Ivo; Duník, Jindřich
2015-11-01
The 12th European Workshop on Advanced Control and Diagnosis (ACD 2015) took place at the Research Centre NTIS - New Technologies for the Information Society, Faculty of Applied Sciences, University of West Bohemia, Pilsen, Czech Republic, on November 19 - 20, 2015. The annual European Workshop on Advanced Control and Diagnosis has been organized since 2003 by Control Engineering departments of several European universities in Germany, France, the UK, Poland, Italy, Hungary, and Denmark to bring together senior and junior academics and engineers from diverse fields of automatic control, fault detection, and signal processing. The workshop provides an opportunity for researchers and developers to present their recent theoretical developments, practical applications, or even open problems. It also offers a great opportunity for industrial partners to express their needs and priorities and to review the current activities in the fields. A total of 74 papers have been submitted for ACD 2015. Based on the peer reviews 48 papers were accepted for the oral presentation and 10 papers for the poster presentation. The accepted papers covered areas of control theory and applications, identification, estimation, signal processing, and fault detection. In addition, four excellent plenary lectures were delivered by Prof. Fredrik Gustafsson (Automotive Sensor Mining for Tire Pressure Monitoring), Prof. Vladimír Havlena (Advanced Process Control for Energy Efficiency), Prof. Silvio Simani (Advanced Issues on Wind Turbine Modelling and Control), and Prof. Robert Babuška (Learning Control in Robotics). The ACD 2015 was for the first time in the workshop history co-sponsored by the International Federation of Automatic Control (IFAC). On behalf of the ACD 2015 organising committee, we would like to thank all those who prepared and submitted papers, participated in the peer review process, supported, and attended the workshop.
Prévost, Alain; Lafitte, Marianne; Pucheu, Yann; Couffinhal, Thierry
2015-03-01
Supervised exercise programs increase physical performance in patients with peripheral artery disease (PAD). However, there are a limited number of programs, and to date they have failed to provide evidence of long-term adherence to exercise or any meaningful effect on Quality of Life (QoL). We created a program of therapeutic education and a personalized program of reconditioning exercise for patients with PAD. Patients with an ankle-brachial index (ABI) below 0.9 in at least one limb, and an absolute claudication distance (ACD) ≤500 meters, were included in the study. Quality of Life (QoL) as measured by SF-36, cardiovascular risk factors and functional parameters were evaluated at 0, 3, 6 and 12 months. Forty-six patients completed the program. Cardiovascular risks were controlled and stabilized over time. SF-36 scores improved significantly and remained stable. Initial and absolute claudication distance (ICD and ACD) as well as other functional parameters improved significantly (6 months: +138 m or +203% ICD and +139 m or +84% ACD). Ten patients (22%) did not show improvement in ICD or ACD within the first 3 months, but their SF-36 score did increase at subsequent visits. Interestingly, these patients had a significantly lower ACD at baseline. This study measured beneficial effects of an educational therapeutic program for patients with PAD. The results demonstrate a significant improvement in functional and QoL parameters during the first 3 months of coaching, and long-term persistence of the results even when patients were no longer coached. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
The role of serum transferrin receptor in the diagnosis of iron deficiency.
Remacha, A F; Sarda, M P; Parellada, M; Ubeda, J; Manteiga, R
1998-11-01
Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.
Mocan, Mehmet Cem; Ustunel, Saim; Dikmetas, Ozlem; Bozkurt, Banu; Irkec, Murat
2014-01-01
The purpose of this study was to evaluate the effect of pharmacologic pupillary dilatation on anterior chamber depth (ACD) and anterior chamber angle (ACA) in eyes with exfoliation syndrome (XFS). Thirty-six eyes of 36 patients with XFS were evaluated with slit-lamp examination, Goldmann applanation tonometry and ultrasound biomicroscopy (UBM) under standard light conditions. Primary outcome parameters were defined as the change in ACD and ACA measured before and 40 min after instillation of a single drop of either 1% cyclopentolate (Group I; n=12), 2.5% phenylephrine (Group II; n=12) or 1% tropicamide (Group III; n=12). Change in intraocular pressure (IOP) during the same time interval was included as a secondary outcome measure. The average predilatation ACD, ACA and IOP values in the study subjects were 2.54±0.40 mm, 27.9±6.3° and 14.9±3.1 mmHg, respectively. There were no significant differences in the mean age (p=0.461), the female/male ratio (p=0.232), baseline ACD (p=0.841), ACA (p=0.761) or IOP (p=0.070) within the three groups. Differences in dilation induced changes in ACD (p=0.108), ACA (p=0.636) and IOP (p=0.160) between the three groups were not statistically significant. Pupillary dilatation with a single drop of 1.0% cyclopentolate, 2.5% phenylephrine or 1% tropicamide is not associated with shallowing of the anterior chamber or narrowing of the ACA in patients with XFS who present with open angles. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.
Park, Seong Bae; Sung, Kyung Rim; Kang, Sung Yung; Jo, Jung Woo; Lee, Kyoung Sub; Kook, Michael S
2011-07-01
To evaluate anterior chamber (AC) angles using gonioscopy, Van Herick technique and anterior segment optical coherence tomography (AS-OCT). One hundred forty-eight consecutive subjects were enrolled. The agreement between any two of three diagnostic methods, gonioscopy, AS-OCT and Van Herick, was calculated in narrow-angle patients. The area under receiver-operating characteristic curves (AUC) for discriminating between narrow and open angles determined by gonioscopy was calculated in all participants for AS-OCT parameter angle opening distance (AOD), angle recess area, trabecular iris surface area and anterior chamber depth (ACD). As a subgroup analysis, capability of AS-OCT parameters for detecting angle closure defined by AS-OCT was assessed in narrow-angle patients. The agreement between the Van Herick method and gonioscopy in detecting angle closure was excellent in narrow angles (κ = 0.80, temporal; κ = 0.82, nasal). However, agreement between gonioscopy and AS-OCT and between the Van Herick method and AS-OCT was poor (κ = 0.11-0.16). Discrimination capability of AS-OCT parameters between open and narrow angles determined by gonioscopy was excellent for all AS-OCT parameters (AUC, temporal: AOD500 = 0.96, nasal: AOD500 = 0.99). The AUCs for detecting angle closure defined by AS-OCT image in narrow angle subjects was good for all AS-OCT parameters (AUC, 0.80-0.94) except for ACD (temporal: ACD = 0.70, nasal: ACD = 0.63). Assessment of narrow angles by gonioscopy and the Van Herick technique showed good agreement, but both measurements revealed poor agreement with AS-OCT. The angle closure detection capability of AS-OCT parameters was excellent; however, it was slightly lower in ACD.
A theoretical Gaussian framework for anomalous change detection in hyperspectral images
NASA Astrophysics Data System (ADS)
Acito, Nicola; Diani, Marco; Corsini, Giovanni
2017-10-01
Exploitation of temporal series of hyperspectral images is a relatively new discipline that has a wide variety of possible applications in fields like remote sensing, area surveillance, defense and security, search and rescue and so on. In this work, we discuss how images taken at two different times can be processed to detect changes caused by insertion, deletion or displacement of small objects in the monitored scene. This problem is known in the literature as anomalous change detection (ACD) and it can be viewed as the extension, to the multitemporal case, of the well-known anomaly detection problem in a single image. In fact, in both cases, the hyperspectral images are processed blindly in an unsupervised manner and without a-priori knowledge about the target spectrum. We introduce the ACD problem using an approach based on the statistical decision theory and we derive a common framework including different ACD approaches. Particularly, we clearly define the observation space, the data statistical distribution conditioned to the two competing hypotheses and the procedure followed to come with the solution. The proposed overview places emphasis on techniques based on the multivariate Gaussian model that allows a formal presentation of the ACD problem and the rigorous derivation of the possible solutions in a way that is both mathematically more tractable and easier to interpret. We also discuss practical problems related to the application of the detectors in the real world and present affordable solutions. Namely, we describe the ACD processing chain including the strategies that are commonly adopted to compensate pervasive radiometric changes, caused by the different illumination/atmospheric conditions, and to mitigate the residual geometric image co-registration errors. Results obtained on real freely available data are discussed in order to test and compare the methods within the proposed general framework.
Preparing adolescents with chronic disease for transition to adult care: a technology program.
Huang, Jeannie S; Terrones, Laura; Tompane, Trevor; Dillon, Lindsay; Pian, Mark; Gottschalk, Michael; Norman, Gregory J; Bartholomew, L Kay
2014-06-01
Adolescents with chronic disease (ACD) must develop independent disease self-management and learn to communicate effectively with their health care team to transition from pediatric to adult-oriented health care systems. Disease-specific interventions have been implemented to aid specific ACD groups through transition. A generic approach might be effective and cost-saving. Eighty-one ACD, aged 12 to 20 years, were recruited for a randomized clinical trial evaluating an 8-month transition intervention (MD2Me). MD2Me recipients received a 2-month intensive Web-based and text-delivered disease management and skill-based intervention followed by a 6-month review period. MD2Me recipients also had access to a texting algorithm for disease assessment and health care team contact. The intervention was applicable to adolescents with diverse chronic illnesses. Controls received mailed materials on general health topics. Disease management, health-related self-efficacy, and health assessments were performed at baseline and at 2 and 8 months. Frequency of patient-initiated communications was recorded over the study period. Outcomes were analyzed according to assigned treatment group over time. MD2Me recipients demonstrated significant improvements in performance of disease management tasks, health-related self-efficacy, and patient-initiated communications compared with controls. Outcomes in ACD improved significantly among recipients of a generic, technology-based intervention. Technology can deliver transition interventions to adolescents with diverse chronic illnesses, and a generic approach offers a cost-effective means of positively influencing transition outcomes. Further research is needed to determine whether improved short-term outcomes translate into an improved transition for ACD. Copyright © 2014 by the American Academy of Pediatrics.
Teaching Cell Division: Basics and Recommendations.
ERIC Educational Resources Information Center
Smith, Mike U.; Kindfield, Ann C. H.
1999-01-01
Presents a concise overview of cell division that includes only the essential concepts necessary for understanding genetics and evolution. Makes recommendations based on published research and teaching experiences that can be used to judge the merits of potential activities and materials for teaching cell division. Makes suggestions regarding the…
2018-01-01
The cell division rate, size and gene expression programmes change in response to external conditions. These global changes impact on average concentrations of biomolecule and their variability or noise. Gene expression is inherently stochastic, and noise levels of individual proteins depend on synthesis and degradation rates as well as on cell-cycle dynamics. We have modelled stochastic gene expression inside growing and dividing cells to study the effect of division rates on noise in mRNA and protein expression. We use assumptions and parameters relevant to Escherichia coli, for which abundant quantitative data are available. We find that coupling of transcription, but not translation rates to the rate of cell division can result in protein concentration and noise homeostasis across conditions. Interestingly, we find that the increased cell size at fast division rates, observed in E. coli and other unicellular organisms, buffers noise levels even for proteins with decreased expression at faster growth. We then investigate the functional importance of these regulations using gene regulatory networks that exhibit bi-stability and oscillations. We find that network topology affects robustness to changes in division rate in complex and unexpected ways. In particular, a simple model of persistence, based on global physiological feedback, predicts increased proportion of persister cells at slow division rates. Altogether, our study reveals how cell size regulation in response to cell division rate could help controlling gene expression noise. It also highlights that understanding circuits' robustness across growth conditions is key for the effective design of synthetic biological systems. PMID:29657814
Allergy to cosmetics: a literature review.
Alani, Jennifer I; Davis, Mark Denis P; Yiannias, James A
2013-01-01
The term cosmetic has a broad definition and includes personal care products, hair care products, nail care products, and sunscreens. Modern cosmetics are safe for most users, and adverse reactions are very rare because the manufacturers invest heavily in safety, quality control, and product testing before releasing the product to the market. Despite these efforts, adverse reactions occur. Skin care products are major contributors to cosmetic allergic contact dermatitis (ACD), followed by hair care and nail care products. The most common allergens are fragrances and preservatives. The diagnosis of cosmetic allergy is established by reviewing the patient's clinical history and physical examination findings and confirmed with skin patch testing. Patch testing is the standard method for detecting allergens responsible for eliciting ACD. The purpose of this article was to review the prevalence, legislative laws, and role of patch testing in ACD.
Symmetric vs. Asymmetric Stem Cell Divisions: An Adaptation against Cancer?
Shahriyari, Leili; Komarova, Natalia L.
2013-01-01
Traditionally, it has been held that a central characteristic of stem cells is their ability to divide asymmetrically. Recent advances in inducible genetic labeling provided ample evidence that symmetric stem cell divisions play an important role in adult mammalian homeostasis. It is well understood that the two types of cell divisions differ in terms of the stem cells' flexibility to expand when needed. On the contrary, the implications of symmetric and asymmetric divisions for mutation accumulation are still poorly understood. In this paper we study a stochastic model of a renewing tissue, and address the optimization problem of tissue architecture in the context of mutant production. Specifically, we study the process of tumor suppressor gene inactivation which usually takes place as a consequence of two “hits”, and which is one of the most common patterns in carcinogenesis. We compare and contrast symmetric and asymmetric (and mixed) stem cell divisions, and focus on the rate at which double-hit mutants are generated. It turns out that symmetrically-dividing cells generate such mutants at a rate which is significantly lower than that of asymmetrically-dividing cells. This result holds whether single-hit (intermediate) mutants are disadvantageous, neutral, or advantageous. It is also independent on whether the carcinogenic double-hit mutants are produced only among the stem cells or also among more specialized cells. We argue that symmetric stem cell divisions in mammals could be an adaptation which helps delay the onset of cancers. We further investigate the question of the optimal fraction of stem cells in the tissue, and quantify the contribution of non-stem cells in mutant production. Our work provides a hypothesis to explain the observation that in mammalian cells, symmetric patterns of stem cell division seem to be very common. PMID:24204602
A genetic screen for temperature-sensitive cell-division mutants of Caenorhabditis elegans.
O'Connell, K F; Leys, C M; White, J G
1998-01-01
A novel screen to isolate conditional cell-division mutants in Caenorhabditis elegans has been developed. The screen is based on the phenotypes associated with existing cell-division mutations: some disrupt postembryonic divisions and affect formation of the gonad and ventral nerve cord-resulting in sterile, uncoordinated animals-while others affect embryonic divisions and result in lethality. We obtained 19 conditional mutants that displayed these phenotypes when shifted to the restrictive temperature at the appropriate developmental stage. Eighteen of these mutations have been mapped; 17 proved to be single alleles of newly identified genes, while 1 proved to be an allele of a previously identified gene. Genetic tests on the embryonic lethal phenotypes indicated that for 13 genes, embryogenesis required maternal expression, while for 6, zygotic expression could suffice. In all cases, maternal expression of wild-type activity was found to be largely sufficient for embryogenesis. Cytological analysis revealed that 10 mutants possessed embryonic cell-division defects, including failure to properly segregate DNA, failure to assemble a mitotic spindle, late cytokinesis defects, prolonged cell cycles, and improperly oriented mitotic spindles. We conclude that this approach can be used to identify mutations that affect various aspects of the cell-division cycle. PMID:9649522
Cell genealogies in a plant meristem deduced with the aid of a 'bootstrap' L-system.
Lück, J; Barlow, P W; Lück, H B
1994-01-01
The primary root meristem of maize (Zea mays L.) contains longitudinal files of cells arranged in groups of familial descent (sisters, cousins, etc.). These groups, or packets, show ordered sequences of cell division which are transverse with respect to the apico-basal axis of the root. The sequences have been analysed in three zones of the meristem during the course of the first four cell generations following germination. In this period, the number of cells in the packets increases from one to 16. Theoretically, there are 48 possible division pathways that lead to the eight-cell stage, and nearly 2 x 10(6) that lead to the 16-cell stage. However, analysis shows that only a few of all the possible pathways are used in any particular zone of the root. This restriction of pathways results from inherited sequences of asymmetric cell divisions which lead to sister cells of unequal length. All possible division pathways can be generated by deterministic 'bootstrap' L-systems which assign different lifespans to sister cells of successive generations and hence specify their subsequent sequence of divisions. These systems simulate propagating patterns of cell divisions which agree with those actually found within the growing packets that comprise the root meristem. The patterns of division are specific to cells originating in various regions of the meristem of the germinating root. The importance of such systems is that they simulate patterns of cellular proliferation where there is ancestral dependency. They can therefore be applied in other growing and proliferating systems where this is suspected.
Rohn, Jennifer L; Patel, Jigna V; Neumann, Beate; Bulkescher, Jutta; Mchedlishvili, Nunu; McMullan, Rachel C; Quintero, Omar A; Ellenberg, Jan; Baum, Buzz
2014-11-03
During animal cell division, an actin-based ring cleaves the cell into two. Problems with this process can cause chromosome missegregation and defects in cytoplasmic inheritance and the partitioning of organelles, which in turn are associated with human diseases. Although much is known about how chromosome segregation is coupled to cell division, the way organelles coordinate their inheritance during partitioning to daughter cells is less well understood. Here, using a high-content live-imaging small interfering RNA screen, we identify Myosin-XIX (Myo19) as a novel regulator of cell division. Previously, this actin-based motor was shown to control the interphase movement of mitochondria. Our analysis shows that Myo19 is indeed localized to mitochondria and that its silencing leads to defects in the distribution of mitochondria within cells and in mitochondrial partitioning at division. Furthermore, many Myo19 RNAi cells undergo stochastic division failure--a phenotype that can be mimicked using a treatment that blocks mitochondrial fission and rescued by decreasing mitochondrial fusion, implying that mitochondria can physically interfere with cytokinesis. Strikingly, using live imaging we also observe the inappropriate movement of mitochondria to the poles of spindles in cells depleted for Myo19 as they enter anaphase. Since this phenocopies the results of an acute loss of actin filaments in anaphase, these data support a model whereby the Myo19 actin-based motor helps to control mitochondrial movement to ensure their faithful segregation during division. The presence of DNA within mitochondria makes their inheritance an especially important aspect of symmetrical cell division. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Cell division is dispensable but not irrelevant in Streptomyces.
McCormick, Joseph R
2009-12-01
In part, members of the genus Streptomyces have been studied because they produce many important secondary metabolites with antibiotic activity and for the interest in their relatively elaborate life cycle. These sporulating filamentous bacteria are remarkably synchronous for division and genome segregation in specialized aerial hyphae. Streptomycetes share some, but not all, of the division genes identified in the historic model rod-shaped organisms. Curiously, normally essential cell division genes are dispensable for growth and viability of Streptomyces coelicolor. Mainly, cell division plays a more important role in the developmental phase of life than during vegetative growth. Dispensability provides an advantageous genetic system to probe the mechanisms of division proteins, especially those with functions that are poorly understood.
Drury, J. P.; Grether, G. F.
2014-01-01
Traits that mediate intraspecific social interactions may overlap in closely related sympatric species, resulting in costly between-species interactions. Such interactions have principally interested investigators studying the evolution of reproductive isolation via reproductive character displacement (RCD) or reinforcement, yet in addition to reproductive interference, interspecific trait overlap can lead to costly between-species aggression. Previous research on rubyspot damselflies (Hetaerina spp.) demonstrated that sympatric shifts in male wing colour patterns and competitor recognition reduce interspecific aggression, supporting the hypothesis that agonistic character displacement (ACD) drove trait shifts. However, a recent theoretical model shows that RCD overshadows ACD if the same male trait is used for both female mate recognition and male competitor recognition. To determine whether female mate recognition is based on male wing coloration in Hetaerina, we conducted a phenotype manipulation experiment. Compared to control males, male H. americana with wings manipulated to resemble a sympatric congener (H. titia) suffered no reduction in mating success. Thus, female mate recognition is not based on species differences in male wing coloration. Experimental males did, however, experience higher interspecific fighting rates and reduced survival compared to controls. These results greatly strengthen the case for ACD and highlight the mechanistic distinction between ACD and RCD. PMID:25339724
Cavallaro, Flaminia; Duca, Lorena; Pisani, Laura Francesca; Rigolini, Roberta; Spina, Luisa; Tontini, Gian Eugenio; Munizio, Nadia; Costa, Elena; Cappellini, Maria Domenica; Vecchi, Maurizio; Pastorelli, Luca
2017-01-01
Background. Anaemia is common in inflammatory bowel disease (IBD), frequently resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). ACD is characterized by macrophage iron retention induced by proinflammatory cytokines. Hepcidin is the master inducer of iron accumulation during ACD, and its production is mainly regulated by IL-6 and the novel erythroid hormone erythroferrone (ERFE). This study evaluates whether anti-TNF monoclonal antibodies therapy modurates hepcidin production and the levels of its main regulators, leading to a restoration of iron homeostasis. Methods. Sera were collected from 21 IBD patients, before each anti-TNF administration, for the first 6 weeks of therapy. Prohepcidin, erythropoietin, erythroferrone, C reactive protein, interleukin-6, iron markers, and haemoglobin levels were measured and clinical activity indexes were evaluated. Results. Serum prohepcidin, IL-6, CRP, and ferritin were significantly reduced after 6-week treatment; an increase in serum iron and total transferrin was observed. No changes in the EPO-ERFE axis were found. Remarkably, haemoglobin was significantly increased. Conclusions. Anti-TNF therapy improves iron metabolism and, subsequently, anaemia in IBD. This effect appears to be related to the modulation of the cytokine network and specifically IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD.
Tension pneumothorax secondary to automatic mechanical compression decompression device.
Hutchings, A C; Darcy, K J; Cumberbatch, G L A
2009-02-01
The details are presented of the first published case of a tension pneumothorax induced by an automatic compression-decompression (ACD) device during cardiac arrest. An elderly patient collapsed with back pain and, on arrival of the crew, was in pulseless electrical activity (PEA) arrest. He was promptly intubated and correct placement of the endotracheal tube was confirmed by noting equal air entry bilaterally and the ACD device applied. On the way to the hospital he was noted to have absent breath sounds on the left without any change in the position of the endotracheal tube. Needle decompression of the left chest caused a hiss of air but the patient remained in PEA. Intercostal drain insertion in the emergency department released a large quantity of air from his left chest but without any change in his condition. Post-mortem examination revealed a ruptured abdominal aortic aneurysm as the cause of death. Multiple left rib fractures and a left lung laceration secondary to the use of the ACD device were also noted, although the pathologist felt that the tension pneumothorax had not contributed to the patient's death. It is recommended that a simple or tension pneumothorax should be considered when there is unilateral absence of breath sounds in addition to endobronchial intubation if an ACD device is being used.
Ocular biometric characteristics of cataract patients in western China.
Huang, Qing; Huang, Yongzhi; Luo, Qu; Fan, Wei
2018-04-17
We aimed to measure ocular biometric characteristics in older cataract patients from western China. Ocular biometry records were retrospectively analyzed for 6933 patients with cataracts (6933 eyes) at least 50 years old who were treated at West China Hospital of Sichuan University. Partial coherence laser interferometry gave the following population averages: axial length (AL), 24.32 ± 2.42 mm; anterior chamber depth (ACD), 3.08 ± 0.47 mm; keratometric power (K), 44.23 ± 1.66 diopters; and corneal astigmatism (CA), 1.00 ± 0.92 diopters. The percentage of individuals with AL > 26.5 mm was 13.66%, while the percentage with CA > 1.0 diopters was 35.54%. Mean AL and ACD showed a trend of decrease with increasing age (P < 0.001). AL correlated positively with ACD (Spearman coefficient, 0.542) and CA (0.111), but negatively with K (- 0.411) (all P < 0.01). K also correlated negatively with ACD (- 0.078, P < 0.01). These results show, for the first time, that older cataract patients from western China have similar ocular biometric characteristics as other populations. The high prevalence of severe axial myopia warrants further investigation.
Functional redundancy of division specific penicillin-binding proteins in Bacillus subtilis.
Sassine, Jad; Xu, Meizhu; Sidiq, Karzan R; Emmins, Robyn; Errington, Jeff; Daniel, Richard A
2017-10-01
Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin-binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β-lactams. © 2017 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.
Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division
Jordan, Shawn N.; Davies, Tim; Zhuravlev, Yelena; Dumont, Julien; Shirasu-Hiza, Mimi
2016-01-01
Cytokinesis, the physical division of one cell into two, is thought to be fundamentally similar in most animal cell divisions and driven by the constriction of a contractile ring positioned and controlled solely by the mitotic spindle. During asymmetric cell divisions, the core polarity machinery (partitioning defective [PAR] proteins) controls the unequal inheritance of key cell fate determinants. Here, we show that in asymmetrically dividing Caenorhabditis elegans embryos, the cortical PAR proteins (including the small guanosine triphosphatase CDC-42) have an active role in regulating recruitment of a critical component of the contractile ring, filamentous actin (F-actin). We found that the cortical PAR proteins are required for the retention of anillin and septin in the anterior pole, which are cytokinesis proteins that our genetic data suggest act as inhibitors of F-actin at the contractile ring. Collectively, our results suggest that the cortical PAR proteins coordinate the establishment of cell polarity with the physical process of cytokinesis during asymmetric cell division to ensure the fidelity of daughter cell formation. PMID:26728855
High frame-rate resolution of cell division during Candida albicans filamentation
Thomson, Darren D.; Berman, Judith; Brand, Alexandra C.
2016-01-01
The commensal yeast, Candida albicans, is an opportunistic pathogen in humans and forms filaments called hyphae and pseudohyphae, in which cell division requires precise temporal and spatial control to produce mononuclear cell compartments. High-frame-rate live-cell imaging (1 frame/min) revealed that nuclear division did not occur across the septal plane. We detected the presence of nucleolar fragments that may be extrachromosomal molecules carrying the ribosomal RNA genes. Cells occasionally maintained multiple nucleoli, suggesting either polyploidy, multiple nuclei and/or aneuploidy of ChrR., while the migration pattern of sister nuclei differed between unbranched and branched hyphae. The presented movie challenges and extends previous concepts of C. albicans cell division. PMID:26854071
A role for the ESCRT system in cell division in archaea.
Samson, Rachel Y; Obita, Takayuki; Freund, Stefan M; Williams, Roger L; Bell, Stephen D
2008-12-12
Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom Crenarchaea, including members of the Sulfolobus genus, encode homologs of the eukaryotic endosomal sorting system components Vps4 and ESCRT-III (endosomal sorting complex required for transport-III). We found that Sulfolobus ESCRT-III and Vps4 homologs underwent regulation of their expression during the cell cycle. The proteins interacted and we established the structural basis of this interaction. Furthermore, these proteins specifically localized to the mid-cell during cell division. Overexpression of a catalytically inactive mutant Vps4 in Sulfolobus resulted in the accumulation of enlarged cells, indicative of failed cell division. Thus, the archaeal ESCRT system plays a key role in cell division.
Spire, an actin nucleation factor, regulates cell division during Drosophila heart development.
Xu, Peng; Johnson, Tamara L; Stoller-Conrad, Jessica R; Schulz, Robert A
2012-01-01
The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir), an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin)-, Even-skipped- and Seven up (Svp)-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate. Furthermore, through visualization of double heterozygous embryos, we determines that spir cooperates with CycA for heart cell specification and division. Finally, when comparing the spir mutant phenotype with that of a CycA mutant, the results suggest that most Svp-positive progenitors in spir mutant embryos cannot undergo full cell division at cell cycle 15, and that Tin-positive progenitors are arrested at cell cycle 16 as double-nucleated cells. We conclude that Spir plays a crucial role in controlling dorsal vessel formation and has a function in cell division during heart tube morphogenesis.
Kamran, Mohammad; Sinha, Swati; Dubey, Priyanka; Lynn, Andrew M; Dhar, Suman K
2016-07-01
Cell division in bacteria is initiated by FtsZ, which forms a Z ring at the middle of the cell, between the nucleoids. The Z ring is stabilized by Z ring-associated proteins (Zaps), which crosslink the FtsZ filaments and provide strength. The deletion of Zaps leads to the elongation phenotype with an abnormal Z ring. The components of cell division in Helicobacter pylori are similar to other gram negative bacteria except for the absence of few components including Zaps. Here, we used HHsearch to identify homologs of the missing cell division proteins and got potential hits for ZapA and ZapB, as well as for few other cell division proteins. We further validated the function of the putative ZapA homolog by genetic complementation, immuno-colocalization and biochemical analysis. © 2016 Federation of European Biochemical Societies.
Prüss, B M
1998-09-01
Carbon sources that can be converted to acetate were added to the growth medium of Escherichia coli wild-type cells. Cells responded with an increased cell division rate. The addition of acetate also caused a decreased synthesis of flagella. Mutants in phosphotransacetylase, which are incapable of synthesizing acetyl phosphate, and mutants in the osmoregulator OmpR divided at a lower rate than did wild-type cells. The mutants did not increase their cell division rate upon the addition of serine, as observed for wild-type cells. These data are consistent with the idea that the previously described effect of serine upon the cell division rate is mediated by acetyl phosphate and phosphorylation of OmpR.
Katayama, T; Takata, M; Sekimizu, K
1997-11-01
We isolated and characterized a new gene related to the control of cell division regulation in Escherichia coli. At 30 degrees C, the dnaAcos mutant causes over-replication of the chromosome, and colony formation is inhibited. We found that, at this temperature, the dnaAcos cells form filaments; therefore, septum formation is inhibited. This inhibition was independent of SfiA, an inhibitor of the septum-forming protein, FtsZ. To identify factors involved in this pathway of inhibition, we isolated seven multicopy suppressors for the cold-sensitive phenotype of the dnaAcos mutant. One of these proved to be a previously unknown gene, which we named cedA. This gene encoded a 12 kDa protein and resided at 38.9min on the E. coli genome map. A multicopy supply of the cedA gene to the dnaAcos cells did not repress over-replication of the chromosome but did stimulate cell division of the host, the result being growth of cells with an abnormally elevated chromosomal copy number. Therefore, the expression level of the cedA gene seems to be important for inhibiting cell division of the dnaAcos mutant at 30 degrees C. We propose that over-replication of the chromosome activates a pathway for inhibiting cell division and that the cedA gene modulates this division control. In the dnaA+ background, cedA also seems to affect cell division.
Takemura, Masahiko; Nakato, Hiroshi
2017-01-15
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration. © 2017. Published by The Company of Biologists Ltd.
2017-01-01
ABSTRACT Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration. PMID:27888216
A method to generate the surface cell layer of the 3D virtual shoot apex from apical initials.
Kucypera, Krzysztof; Lipowczan, Marcin; Piekarska-Stachowiak, Anna; Nakielski, Jerzy
2017-01-01
The development of cell pattern in the surface cell layer of the shoot apex can be investigated in vivo by use of a time-lapse confocal images, showing naked meristem in 3D in successive times. However, how this layer is originated from apical initials and develops as a result of growth and divisions of their descendants, remains unknown. This is an open area for computer modelling. A method to generate the surface cell layer is presented on the example of the 3D paraboloidal shoot apical dome. In the used model the layer originates from three apical initials that meet at the dome summit and develops through growth and cell divisions under the isotropic surface growth, defined by the growth tensor. The cells, which are described by polyhedrons, divide anticlinally with the smallest division plane that passes depending on the used mode through the cell center, or the point found randomly near this center. The formation of the surface cell pattern is described with the attention being paid to activity of the apical initials and fates of their descendants. The computer generated surface layer that included about 350 cells required about 1200 divisions of the apical initials and their derivatives. The derivatives were arranged into three more or less equal clonal sectors composed of cellular clones at different age. Each apical initial renewed itself 7-8 times to produce the sector. In the shape and location and the cellular clones the following divisions of the initial were manifested. The application of the random factor resulted in more realistic cell pattern in comparison to the pure mode. The cell divisions were analyzed statistically on the top view. When all of the division walls were considered, their angular distribution was uniform, whereas in the distribution that was limited to apical initials only, some preferences related to their arrangement at the dome summit were observed. The realistic surface cell pattern was obtained. The present method is a useful tool to generate surface cell layer, study activity of initial cells and their derivatives, and how cell expansion and division are coordinated during growth. We expect its further application to clarify the question of a number and permanence or impermanence of initial cells, and possible relationship between their shape and oriented divisions, both on the ground of the growth tensor approach.
Using "Chromosomal Socks" to Demonstrate Ploidy in Mitosis and Meiosis
ERIC Educational Resources Information Center
Chinnici, Joseph P.; Neth, Somalin Zaroh; Sherman, Leah R.
2006-01-01
Today, many biology instructors use visual models to help students understand abstract concepts like cell division. For all biology instructors, dealing with student misconceptions of cell division may seem hopeless at times--even after using visual models. Although student errors in cell division are built around the three key events of cell…
Pilhofer, Martin; Rappl, Kristina; Eckl, Christina; Bauer, Andreas Peter; Ludwig, Wolfgang; Schleifer, Karl-Heinz; Petroni, Giulio
2008-01-01
In the past, studies on the relationships of the bacterial phyla Planctomycetes, Chlamydiae, Lentisphaerae, and Verrucomicrobia using different phylogenetic markers have been controversial. Investigations based on 16S rRNA sequence analyses suggested a relationship of the four phyla, showing the branching order Planctomycetes, Chlamydiae, Verrucomicrobia/Lentisphaerae. Phylogenetic analyses of 23S rRNA genes in this study also support a monophyletic grouping and their branching order—this grouping is significant for understanding cell division, since the major bacterial cell division protein FtsZ is absent from members of two of the phyla Chlamydiae and Planctomycetes. In Verrucomicrobia, knowledge about cell division is mainly restricted to the recent report of ftsZ in the closely related genera Prosthecobacter and Verrucomicrobium. In this study, genes of the conserved division and cell wall (dcw) cluster (ddl, ftsQ, ftsA, and ftsZ) were characterized in all verrucomicrobial subdivisions (1 to 4) with cultivable representatives (1 to 4). Sequence analyses and transcriptional analyses in Verrucomicrobia and genome data analyses in Lentisphaerae suggested that cell division is based on FtsZ in all verrucomicrobial subdivisions and possibly also in the sister phylum Lentisphaerae. Comprehensive sequence analyses of available genome data for representatives of Verrucomicrobia, Lentisphaerae, Chlamydiae, and Planctomycetes strongly indicate that their last common ancestor possessed a conserved, ancestral type of dcw gene cluster and an FtsZ-based cell division mechanism. This implies that Planctomycetes and Chlamydiae may have shifted independently to a non-FtsZ-based cell division mechanism after their separate branchings from their last common ancestor with Verrucomicrobia. PMID:18310338
NASA Technical Reports Server (NTRS)
Honda, Shuji; Nelson, Gregory; Schubert, Wayne
1993-01-01
Intestinal cells when subjected to oxidative stress or radiation exhibit abnormal nuclear divisions observed as: 1) supernumerary cell divisions in anterior intestinal cells or 2) incomplete nuclear division and the persistence of anaphase bridges between daughter nuclei. Two oxygen sensitive mutants, mev-1 and rad-8 were observed to exhibit spontaneous supernumerary nuclear divisions at low frequency. N2 can be induced to undergo these divisions by treatment with the superoxide dismutase (SOD) inhibitor diethyl dithicarbamate or with the free radical generator methyl viologen. By contrast, the free radical generator bleomycin produces anaphase bridges in N2 intestinal nuclei at high frequency. Intestinal anaphase bridges can be induced by ionizing radiation and their formation is dependent on dose and radiation type.
Time-Lapse Cinemicrographic Studies of X-Irradiated HeLa S3 Cells
Hurwitz, Camilla; Tolmach, L. J.
1969-01-01
Analysis of time-lapse cinemicrographs of X-irradiated HeLa S3 cells has shown that the incidence of cell fusion was increased from 0.9% (following 1267 divisions) in control cells to an average of 22% (following 655 divisions) in cells irradiated with 500 rad doses of 220 kv X-rays. The incidence depended on the stage of the generation cycle at which the parent cells were irradiated. It was nearly constant in the first three postirradiation generations. Fusion occurred at all stages of the generation cycle, but preferentially during the first 20%. Cells undergoing fusion progressed more slowly through the generation cycle and had a higher probability of disintegrating than did irradiated cells that did not fuse. The occurrence of fusion was clonally distributed in the population. It took place only between sister (or closely related) cells. Protoplasmic bridges were often visible between sister cells prior to fusion. Giant cells arose only as a result of fusion. The incidence of multipolar divisions, though higher than in unirradiated cells, was only 5.5% in cultures irradiated with 500 rads. Fusion occurred following 85% of the multipolar divisions and was often followed by a multipolar division. ImagesFigure 1 PMID:5807221
Asl, Leila Kheibarshekan; Dhondt, Stijn; Boudolf, Véronique; Beemster, Gerrit T S; Beeckman, Tom; Inzé, Dirk; Govaerts, Willy; De Veylder, Lieven
2011-08-01
To efficiently capture sunlight for photosynthesis, leaves typically develop into a flat and thin structure. This development is driven by cell division and expansion, but the individual contribution of these processes is currently unknown, mainly because of the experimental difficulties to disentangle them in a developing organ, due to their tight interconnection. To circumvent this problem, we built a mathematic model that describes the possible division patterns and expansion rates for individual epidermal cells. This model was used to fit experimental data on cell numbers and sizes obtained over time intervals of 1 d throughout the development of the first leaf pair of Arabidopsis (Arabidopsis thaliana). The parameters were obtained by a derivative-free optimization method that minimizes the differences between the predicted and experimentally observed cell size distributions. The model allowed us to calculate probabilities for a cell to divide into guard or pavement cells, the maximum size at which it can divide, and its average cell division and expansion rates at each point during the leaf developmental process. Surprisingly, average cell cycle duration remained constant throughout leaf development, whereas no evidence for a maximum cell size threshold for cell division of pavement cells was found. Furthermore, the model predicted that neighboring cells of different sizes within the epidermis expand at distinctly different relative rates, which could be verified by direct observations. We conclude that cell division seems to occur independently from the status of cell expansion, whereas the cell cycle might act as a timer rather than as a size-regulated machinery.
Asl, Leila Kheibarshekan; Dhondt, Stijn; Boudolf, Véronique; Beemster, Gerrit T.S.; Beeckman, Tom; Inzé, Dirk; Govaerts, Willy; De Veylder, Lieven
2011-01-01
To efficiently capture sunlight for photosynthesis, leaves typically develop into a flat and thin structure. This development is driven by cell division and expansion, but the individual contribution of these processes is currently unknown, mainly because of the experimental difficulties to disentangle them in a developing organ, due to their tight interconnection. To circumvent this problem, we built a mathematic model that describes the possible division patterns and expansion rates for individual epidermal cells. This model was used to fit experimental data on cell numbers and sizes obtained over time intervals of 1 d throughout the development of the first leaf pair of Arabidopsis (Arabidopsis thaliana). The parameters were obtained by a derivative-free optimization method that minimizes the differences between the predicted and experimentally observed cell size distributions. The model allowed us to calculate probabilities for a cell to divide into guard or pavement cells, the maximum size at which it can divide, and its average cell division and expansion rates at each point during the leaf developmental process. Surprisingly, average cell cycle duration remained constant throughout leaf development, whereas no evidence for a maximum cell size threshold for cell division of pavement cells was found. Furthermore, the model predicted that neighboring cells of different sizes within the epidermis expand at distinctly different relative rates, which could be verified by direct observations. We conclude that cell division seems to occur independently from the status of cell expansion, whereas the cell cycle might act as a timer rather than as a size-regulated machinery. PMID:21693673
Division of Labor in Biofilms: the Ecology of Cell Differentiation.
van Gestel, Jordi; Vlamakis, Hera; Kolter, Roberto
2015-04-01
The dense aggregation of cells on a surface, as seen in biofilms, inevitably results in both environmental and cellular heterogeneity. For example, nutrient gradients can trigger cells to differentiate into various phenotypic states. Not only do cells adapt physiologically to the local environmental conditions, but they also differentiate into cell types that interact with each other. This allows for task differentiation and, hence, the division of labor. In this article, we focus on cell differentiation and the division of labor in three bacterial species: Myxococcus xanthus, Bacillus subtilis, and Pseudomonas aeruginosa. During biofilm formation each of these species differentiates into distinct cell types, in some cases leading to cooperative interactions. The division of labor and the cooperative interactions between cell types are assumed to yield an emergent ecological benefit. Yet in most cases the ecological benefits have yet to be elucidated. A notable exception is M. xanthus, in which cell differentiation within fruiting bodies facilitates the dispersal of spores. We argue that the ecological benefits of the division of labor might best be understood when we consider the dynamic nature of both biofilm formation and degradation.
Molecular coordination of Staphylococcus aureus cell division
Cotterell, Bryony E; Walther, Christa G; Fenn, Samuel J; Grein, Fabian; Wollman, Adam JM; Leake, Mark C; Olivier, Nicolas; Cadby, Ashley; Mesnage, Stéphane; Jones, Simon
2018-01-01
The bacterial cell wall is essential for viability, but despite its ability to withstand internal turgor must remain dynamic to permit growth and division. Peptidoglycan is the major cell wall structural polymer, whose synthesis requires multiple interacting components. The human pathogen Staphylococcus aureus is a prolate spheroid that divides in three orthogonal planes. Here, we have integrated cellular morphology during division with molecular level resolution imaging of peptidoglycan synthesis and the components responsible. Synthesis occurs across the developing septal surface in a diffuse pattern, a necessity of the observed septal geometry, that is matched by variegated division component distribution. Synthesis continues after septal annulus completion, where the core division component FtsZ remains. The novel molecular level information requires re-evaluation of the growth and division processes leading to a new conceptual model, whereby the cell cycle is expedited by a set of functionally connected but not regularly distributed components. PMID:29465397
Peptidoglycan architecture can specify division planes in Staphylococcus aureus.
Turner, Robert D; Ratcliffe, Emma C; Wheeler, Richard; Golestanian, Ramin; Hobbs, Jamie K; Foster, Simon J
2010-06-15
Division in Staphylococci occurs equatorially and on specific sequentially orthogonal planes in three dimensions, resulting, after incomplete cell separation, in the 'bunch of grapes' cluster organization that defines the genus. The shape of Staphylococci is principally maintained by peptidoglycan. In this study, we use Atomic Force Microscopy (AFM) and fluorescence microscopy with vancomycin labelling to examine purified peptidoglycan architecture and its dynamics in Staphylococcus aureus and correlate these with the cell cycle. At the presumptive septum, cells were found to form a large belt of peptidoglycan in the division plane before the centripetal formation of the septal disc; this often had a 'piecrust' texture. After division, the structures remain as orthogonal ribs, encoding the location of past division planes in the cell wall. We propose that this epigenetic information is used to enable S. aureus to divide in sequentially orthogonal planes, explaining how a spherical organism can maintain division plane localization with fidelity over many generations.
Unified quantitative characterization of epithelial tissue development
Guirao, Boris; Rigaud, Stéphane U; Bosveld, Floris; Bailles, Anaïs; López-Gay, Jesús; Ishihara, Shuji; Sugimura, Kaoru
2015-01-01
Understanding the mechanisms regulating development requires a quantitative characterization of cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that relates the characterizations of each cell process to tissue growth and morphogenesis. Having validated the formalism on computer simulations, we quantified separately all morphogenetic events in the Drosophila dorsal thorax and wing pupal epithelia to obtain comprehensive statistical maps linking cell and tissue scale dynamics. While globally cell shape changes, rearrangements and divisions all significantly participate in tissue morphogenesis, locally, their relative participations display major variations in space and time. By blocking division we analyzed the impact of division on rearrangements, cell shape changes and tissue morphogenesis. Finally, by combining the formalism with mechanical stress measurement, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development. DOI: http://dx.doi.org/10.7554/eLife.08519.001 PMID:26653285
Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures
Cerruti, Benedetta; Puliafito, Alberto; Shewan, Annette M.; Yu, Wei; Combes, Alexander N.; Little, Melissa H.; Chianale, Federica; Primo, Luca; Serini, Guido; Mostov, Keith E.; Celani, Antonio
2013-01-01
The growth of a well-formed epithelial structure is governed by mechanical constraints, cellular apico-basal polarity, and spatially controlled cell division. Here we compared the predictions of a mathematical model of epithelial growth with the morphological analysis of 3D epithelial structures. In both in vitro cyst models and in developing epithelial structures in vivo, epithelial growth could take place close to or far from mechanical equilibrium, and was determined by the hierarchy of time-scales of cell division, cell–cell rearrangements, and lumen dynamics. Equilibrium properties could be inferred by the analysis of cell–cell contact topologies, and the nonequilibrium phenotype was altered by inhibiting ROCK activity. The occurrence of an aberrant multilumen phenotype was linked to fast nonequilibrium growth, even when geometric control of cell division was correctly enforced. We predicted and verified experimentally that slowing down cell division partially rescued a multilumen phenotype induced by altered polarity. These results improve our understanding of the development of epithelial organs and, ultimately, of carcinogenesis. PMID:24145168
Jacq, Maxime; Arthaud, Christopher; Manuse, Sylvie; Mercy, Chryslène; Bellard, Laure; Peters, Katharina; Gallet, Benoit; Galindo, Jennifer; Doan, Thierry; Vollmer, Waldemar; Brun, Yves V; VanNieuwenhze, Michael S; Di Guilmi, Anne Marie; Vernet, Thierry; Grangeasse, Christophe; Morlot, Cecile
2018-05-15
Bacterial division is intimately linked to synthesis and remodeling of the peptidoglycan, a cage-like polymer that surrounds the bacterial cell, providing shape and mechanical resistance. The bacterial division machinery, which is scaffolded by the cytoskeleton protein FtsZ, includes proteins with enzymatic, structural or regulatory functions. These proteins establish a complex network of transient functional and/or physical interactions which preserve cell shape and cell integrity. Cell wall hydrolases required for peptidoglycan remodeling are major contributors to this mechanism. Consistent with this, their deletion or depletion often results in morphological and/or division defects. However, the exact function of most of them remains elusive. In this work, we show that the putative lysozyme activity of the cell wall hydrolase Pmp23 is important for proper morphology and cell division in the opportunistic human pathogen Streptococcus pneumoniae. Our data indicate that active Pmp23 is required for proper localization of the Z-ring and the FtsZ-positioning protein MapZ. In addition, Pmp23 localizes to the division site and interacts directly with the essential peptidoglycan synthase PBP2x. Altogether, our data reveal a new regulatory function for peptidoglycan hydrolases.
Peterson, Kylee M; Torii, Keiko U
2012-12-31
Imaging in vivo dynamics of cellular behavior throughout a developmental sequence can be a powerful technique for understanding the mechanics of tissue patterning. During animal development, key cell proliferation and patterning events occur very quickly. For instance, in Caenorhabditis elegans all cell divisions required for the larval body plan are completed within six hours after fertilization, with seven mitotic cycles(1); the sixteen or more mitoses of Drosophila embryogenesis occur in less than 24 hr(2). In contrast, cell divisions during plant development are slow, typically on the order of a day (3,4,5) . This imposes a unique challenge and a need for long-term live imaging for documenting dynamic behaviors of cell division and differentiation events during plant organogenesis. Arabidopsis epidermis is an excellent model system for investigating signaling, cell fate, and development in plants. In the cotyledon, this tissue consists of air- and water-resistant pavement cells interspersed with evenly distributed stomata, valves that open and close to control gas exchange and water loss. Proper spacing of these stomata is critical to their function, and their development follows a sequence of asymmetric division and cell differentiation steps to produce the organized epidermis (Fig. 1). This protocol allows observation of cells and proteins in the epidermis over several days of development. This time frame enables precise documentation of stem-cell divisions and differentiation of epidermal cells, including stomata and epidermal pavement cells. Fluorescent proteins can be fused to proteins of interest to assess their dynamics during cell division and differentiation processes. This technique allows us to understand the localization of a novel protein, POLAR(6), during the proliferation stage of stomatal-lineage cells in the Arabidopsis cotyledon epidermis, where it is expressed in cells preceding asymmetric division events and moves to a characteristic area of the cell cortex shortly before division occurs. Images can be registered and streamlined video easily produced using public domain software to visualize dynamic protein localization and cell types as they change over time.
Fairley, D J; Wang, G; Rensing, C; Pepper, I L; Larkin, M J
2006-12-01
Gentisate-1,2-dioxygenase genes (gdoA), with homology to a number of bacterial dioxygenases, and genes encoding a putative coenzyme A (CoA)-synthetase subunit (acdB) and a CoA-thioesterase (tieA) were identified in two haloarchaeal isolates. In Haloarcula sp. D1, gdoA was expressed during growth on 4-hydroxybenzoate but not benzoate, and acdB and tieA were not expressed during growth on any of the aromatic substrates tested. In contrast, gdoA was expressed in Haloferax sp. D1227 during growth on benzoate, 3-hydroxybenzoate, cinnamate and phenylpropionate, and both acdB and tieA were expressed during growth on benzoate, cinnamate and phenylpropionate, but not on 3-hydroxybenzoate. This pattern of induction is consistent with these genes encoding steps in a CoA-mediated benzoate pathway in this strain.
TOPAZ II Anti-Criticality Device Rapid Prototype
NASA Astrophysics Data System (ADS)
Campbell, Donald R.; Otting, William D.
1994-07-01
The Ballistic Missile Defense Organization (BMDO) has been working on a Nuclear Electric Propulsion Space Test Project (NEPSTP) using an existing Russian Topaz II reactor system to power the NEPSTP satellite. Safety investigations have shown that it will be possible to safely launch the Topaz II system in the United States with some modification to preclude water flooded criticality. A ``fuel-out'' water subcriticality concept was selected by the Los Alamos National Laboratory (LANL) as the baseline concept. A fuel-out anti-criticality device (ACD) conceptual design was developed by Rockwell. The concept functions to hold the fuel from the four centermost thermionic fuel elements (TFEs) outside the reactor during launch and reliably inserts the fuel into the reactor once the operational orbit is achieved. A four-tenths scale ACD rapid prototype model, fabricated from the CATIA solids design model, clearly shows in three dimensions the relative size and spatial relationship of the ACD components.
Chen, Jennifer K; Jacob, Sharon E; Nedorost, Susan T; Hanifin, Jon M; Simpson, Eric L; Boguniewicz, Mark; Watsky, Kalman L; Lugo-Somolinos, Aida; Hamann, Carsten R; Eberting, Cheryl Lee; Silverberg, Jonathan I; Thyssen, Jacob P
2016-01-01
Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.
PREFERED SURGICAL TECHNIQUE USED BY ORTHOPEDISTS IN ACUTE ACROMIOCLAVICULAR DISLOCATION
NISHIMI, ALEXANDRE YUKIO; ARBEX, DEMETRIO SIMÃO; MARTINS, DIOGO LUCAS CAMPOS; GUSMÃO, CARLOS VINICIUS BUARQUE DE; BONGIOVANNI, ROBERTO RANGEL; PASCARELLI, LUCIANO
2016-01-01
ABSTRACT Objective: To determine whether training on shoulder and elbow surgery influences the orthopedist surgeons' preferred technique to address acute acromioclavicular joint dislocation (ACD). Methods: A survey was conducted with shoulder and elbow specialists and general orthopedists on their preferred technique to address acute ACD. Results: Thirty specialists and forty-five general orthopedists joined the study. Most specialists preferred the endobutton technique, while most general orthopedists preferred the modified Phemister procedure for coracoclavicular ligament repair using anchors. We found no difference between specialists and general orthopedists in the number of tunnels used to repair the coracoclavicular ligament; preferred method for wire insertion through the clavicular tunnels; buried versus unburied Kirschner wire insertion for acromioclavicular temporary fixation; and time for its removal; and regarding the suture thread used for deltotrapezoidal fascia closure. Conclusion: Training on shoulder and elbow surgery influences the surgeons' preferred technique to address acute ACD. Level of Evidence V, Expert Opinion. PMID:28149190
BASL and EPF2 act independently to regulate asymmetric divisions during stomatal development
Hunt, Lee
2010-01-01
The initiation of stomatal development in the developing Arabidopsis epidermis is characterized by an asymmetric ‘entry’ division in which a small cell, known as a meristemoid, and a larger daughter cell is formed. The meristemoid may undergo further asymmetric divisions, regenerating a meristemoid each time, before differentiating into a guard mother cell which divides symmetrically to form a pair of guard cells surrounding a stomatal pore. Recently EPF2 and BASL have emerged as regulators of these asymmetric divisions and here we present results indicating that these two factors operate independently to control stomatal development PMID:20220310
Tissue damage-induced intestinal stem cell division in Drosophila
Amcheslavsky, Alla; Jiang, Jin; Ip, Y. Tony
2009-01-01
SUMMARY Stem cell division is essential for tissue integrity during growth, aging, and pathogenic assaults. Adult gastrointestinal tract encounters numerous stimulations and impaired tissue regeneration may lead to inflammatory diseases and cancer. Intestinal stem cells in adult Drosophila have recently been identified and shown to replenish the various cell types within the midgut. However, it is not known whether these intestinal stem cells can respond to environmental challenges. By feeding dextran sulfate sodium and bleomycin to flies and by expressing apoptotic proteins, we show that Drosophila intestinal stem cells can increase the rate of division in response to tissue damage. Moreover, if tissue damage results in epithelial cell loss, the newly formed enteroblasts can differentiate into mature epithelial cells. By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. PMID:19128792
Cell Division and Evolution of Biological Tissues
NASA Astrophysics Data System (ADS)
Rivier, Nicolas; Arcenegui-Siemens, Xavier; Schliecker, Gudrun
A tissue is a geometrical, space-filling, random cellular network; it remains in this steady state while individual cells divide. Cell division (fragmentation) is a local, elementary topological transformation which establishes statistical equilibrium of the structure. Statistical equilibrium is characterized by observable relations (Lewis, Aboav) between cell shapes, sizes and those of their neighbours, obtained through maximum entropy and topological correlation extending to nearest neighbours only, i.e. maximal randomness. For a two-dimensional tissue (epithelium), the distribution of cell shapes and that of mother and daughter cells can be obtained from elementary geometrical and physical arguments, except for an exponential factor favouring division of larger cells, and exponential and combinatorial factors encouraging a most symmetric division. The resulting distributions are very narrow, and stationarity severely restricts the range of an adjustable structural parameter
Cytokinesis: breaking the ties that bind.
McCollum, Dannel
2005-12-20
It has been unclear how cells complete cell division and resolve membrane connections to bring about cell separation. Recent work has shown that targeted secretion to the midbody is required to complete cell division.
ERIC Educational Resources Information Center
Kara, Yilmaz; Yesilyurt, Selami
2008-01-01
The purpose of this study was to investigate the effects of tutorial and edutainment design of instructional software programs related to the "cell division" topic on student achievements, misconceptions and attitudes. An experimental research design including the cell division achievement test (CAT), the cell division concept test (CCT) and…
Honda, Takashi; Morimoto, Daichi; Sako, Yoshihiko; Yoshida, Takashi
2018-05-17
Previously, we showed that DNA replication and cell division in toxic cyanobacterium Microcystis aeruginosa are coordinated by transcriptional regulation of cell division gene ftsZ and that an unknown protein specifically bound upstream of ftsZ (BpFz; DNA-binding protein to an upstream site of ftsZ) during successful DNA replication and cell division. Here, we purified BpFz from M. aeruginosa strain NIES-298 using DNA-affinity chromatography and gel-slicing combined with gel electrophoresis mobility shift assay (EMSA). The N-terminal amino acid sequence of BpFz was identified as TNLESLTQ, which was identical to that of transcription repressor LexA from NIES-843. EMSA analysis using mutant probes showed that the sequence GTACTAN 3 GTGTTC was important in LexA binding. Comparison of the upstream regions of lexA in the genomes of closely related cyanobacteria suggested that the sequence TASTRNNNNTGTWC could be a putative LexA recognition sequence (LexA box). Searches for TASTRNNNNTGTWC as a transcriptional regulatory site (TRS) in the genome of M. aeruginosa NIES-843 showed that it was present in genes involved in cell division, photosynthesis, and extracellular polysaccharide biosynthesis. Considering that BpFz binds to the TRS of ftsZ during normal cell division, LexA may function as a transcriptional activator of genes related to cell reproduction in M. aeruginosa, including ftsZ. This may be an example of informality in the control of bacterial cell division.
NASA Astrophysics Data System (ADS)
Roy, Ronald A.
2004-05-01
Robert Apfel believed in the creative application of acoustics technology to difficult problems in biomedical sensing. Much of his work in this area focused on material characterization, with the intention of effecting diagnosis. His early work in blood cell characterization employed acoustic levitation to measure the bulk mechanical properties of human red blood cells. This subsequently paved the way to the use of high-frequency acoustic scattering to yield the compressibility and density of individual blood cells. Technology developed in this later effort was then adapted to the very difficult problem of transient micro-cavitation detection, and the active cavitation detector (ACD) was born. This paper traces this line of work from its origins and, in the process, serves to celebrate Bob Apfel's peerless ingenuity and irrepressible creativity.
A theory of germinal center B cell selection, division, and exit.
Meyer-Hermann, Michael; Mohr, Elodie; Pelletier, Nadége; Zhang, Yang; Victora, Gabriel D; Toellner, Kai-Michael
2012-07-26
High-affinity antibodies are generated in germinal centers in a process involving mutation and selection of B cells. Information processing in germinal center reactions has been investigated in a number of recent experiments. These have revealed cell migration patterns, asymmetric cell divisions, and cell-cell interaction characteristics, used here to develop a theory of germinal center B cell selection, division, and exit (the LEDA model). According to this model, B cells selected by T follicular helper cells on the basis of successful antigen processing always return to the dark zone for asymmetric division, and acquired antigen is inherited by one daughter cell only. Antigen-retaining B cells differentiate to plasma cells and leave the germinal center through the dark zone. This theory has implications for the functioning of germinal centers because compared to previous models, high-affinity antibodies appear one day earlier and the amount of derived plasma cells is considerably larger. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.
Comparison of the new biometer OA-1000 with IOLMaster and Tomey AL-3000.
Goebels, Susanne Christiane; Seitz, Berthold; Langenbucher, Achim
2013-09-01
The OA-1000 (Tomey, Japan) is a new optical biometer, which allows measurements of axial length (AL), anterior chamber depth (ACD) and corneal thickness (CT) due to partial coherence interferometry (PCI) technology. The aim of this study was to compare the OA-1000 results with those obtained with the IOLMaster and contact applanation A-scan ultrasonography. We examined 133 eyes of 75 patients with age related cataract. Mean age was 72.0 ± 9.5 years. Biometry measurements of AL and ACD were performed with the Tomey OA-1000 based on PCI, the IOLMaster based on PCI (AL) and slit projection (ACD), and the Tomey AL-3000 based on contact applanation A-scan ultrasonography. Mean AL using the IOLMaster was 23.21 ± 1.08 mm, using the AL-3000 was 22.79 ± 1.04 mm, using the OA-1000 it was 22.97 ± 1.1 mm. Mean ACD using the IOLMaster was 2.99 ± 0.41 mm, using the OA-1000 3.40 ± 0.46 mm, using the Tomey AL-3000 it was 2.93 ± 0.43 mm. Mean difference between the AL and ACD measured with the OA-1000 and the IOLMaster was 0.22 ± 0.047 mm and 0.40 ± 0.33 mm, between OA-1000 and the AL-3000 it was 0.19 ± 0.23 mm and 0.47 ± 0.33 mm, and between IOLMaster and AL-3000 it was 0.42 ± 0.23 and 0.09 ± 0.36 mm. For AL the correlation coefficient R between IOLMaster and OA-1000 was 0.999, between IOLMaster and AL-3000 it was 0.976, between AL-3000 and OA-1000 it was 0.977. For ACD R between IOLMaster and OA-1000 was 0.735, between IOLMaster and AL-3000 it was 0.822, between AL-3000 and OA-1000 it was 0.716 (all p < 0.001). Compared with other used clinical instruments the OA-1000 generates accurate results. Although differences were found, the OA-1000 provided results that correlated well with the values of IOLMaster and AL-3000.
Oriented cell division shapes carnivorous pitcher leaves of Sarracenia purpurea
Fukushima, Kenji; Fujita, Hironori; Yamaguchi, Takahiro; Kawaguchi, Masayoshi; Tsukaya, Hirokazu; Hasebe, Mitsuyasu
2015-01-01
Complex morphology is an evolutionary outcome of phenotypic diversification. In some carnivorous plants, the ancestral planar leaf has been modified to form a pitcher shape. However, how leaf development was altered during evolution remains unknown. Here we show that the pitcher leaves of Sarracenia purpurea develop through cell division patterns of adaxial tissues that are distinct from those in bifacial and peltate leaves, subsequent to standard expression of adaxial and abaxial marker genes. Differences in the orientation of cell divisions in the adaxial domain cause bifacial growth in the distal region and adaxial ridge protrusion in the middle region. These different growth patterns establish pitcher morphology. A computer simulation suggests that the cell division plane is critical for the pitcher morphogenesis. Our results imply that tissue-specific changes in the orientation of cell division underlie the development of a morphologically complex leaf. PMID:25774486
Oriented cell division shapes carnivorous pitcher leaves of Sarracenia purpurea.
Fukushima, Kenji; Fujita, Hironori; Yamaguchi, Takahiro; Kawaguchi, Masayoshi; Tsukaya, Hirokazu; Hasebe, Mitsuyasu
2015-03-16
Complex morphology is an evolutionary outcome of phenotypic diversification. In some carnivorous plants, the ancestral planar leaf has been modified to form a pitcher shape. However, how leaf development was altered during evolution remains unknown. Here we show that the pitcher leaves of Sarracenia purpurea develop through cell division patterns of adaxial tissues that are distinct from those in bifacial and peltate leaves, subsequent to standard expression of adaxial and abaxial marker genes. Differences in the orientation of cell divisions in the adaxial domain cause bifacial growth in the distal region and adaxial ridge protrusion in the middle region. These different growth patterns establish pitcher morphology. A computer simulation suggests that the cell division plane is critical for the pitcher morphogenesis. Our results imply that tissue-specific changes in the orientation of cell division underlie the development of a morphologically complex leaf.
Chlamydia co-opts the rod shape-determining proteins MreB and Pbp2 for cell division.
Ouellette, Scot P; Karimova, Gouzel; Subtil, Agathe; Ladant, Daniel
2012-07-01
Chlamydiae are obligate intracellular bacterial pathogens that have extensively reduced their genome in adapting to the intracellular environment. The chlamydial genome contains only three annotated cell division genes and lacks ftsZ. How this obligate intracellular pathogen divides is uncharacterized. Chlamydiae contain two high-molecular-weight (HMW) penicillin binding proteins (Pbp) implicated in peptidoglycan synthesis, Pbp2 and Pbp3/FtsI. We show here, using HMW Pbp-specific penicillin derivatives, that both Pbp2 and Pbp3 are essential for chlamydial cell division. Ultrastructural analyses of antibiotic-treated cultures revealed distinct phenotypes: Pbp2 inhibition induced internal cell bodies within a single outer membrane whereas Pbp3 inhibition induced elongated phenotypes with little internal division. Each HMW Pbp interacts with the Chlamydia cell division protein FtsK. Chlamydiae are coccoid yet contain MreB, a rod shape-determining protein linked to Pbp2 in bacilli. Using MreB-specific antibiotics, we show that MreB is essential for chlamydial growth and division. Importantly, co-treatment with MreB-specific and Pbp-specific antibiotics resulted in the MreB-inhibited phenotype, placing MreB upstream of Pbp function in chlamydial cell division. Finally, we showed that MreB also interacts with FtsK. We propose that, in Chlamydia, MreB acts as a central co-ordinator at the division site to substitute for the lack of FtsZ in this bacterium. © 2012 Blackwell Publishing Ltd.
CD8 Memory Cells Develop Unique DNA Repair Mechanisms Favoring Productive Division.
Galgano, Alessia; Barinov, Aleksandr; Vasseur, Florence; de Villartay, Jean-Pierre; Rocha, Benedita
2015-01-01
Immune responses are efficient because the rare antigen-specific naïve cells are able to proliferate extensively and accumulate upon antigen stimulation. Moreover, differentiation into memory cells actually increases T cell accumulation, indicating improved productive division in secondary immune responses. These properties raise an important paradox: how T cells may survive the DNA lesions necessarily induced during their extensive division without undergoing transformation. We here present the first data addressing the DNA damage responses (DDRs) of CD8 T cells in vivo during exponential expansion in primary and secondary responses in mice. We show that during exponential division CD8 T cells engage unique DDRs, which are not present in other exponentially dividing cells, in T lymphocytes after UV or X irradiation or in non-metastatic tumor cells. While in other cell types a single DDR pathway is affected, all DDR pathways and cell cycle checkpoints are affected in dividing CD8 T cells. All DDR pathways collapse in secondary responses in the absence of CD4 help. CD8 T cells are driven to compulsive suicidal divisions preventing the propagation of DNA lesions. In contrast, in the presence of CD4 help all the DDR pathways are up regulated, resembling those present in metastatic tumors. However, this up regulation is present only during the expansion phase; i.e., their dependence on antigen stimulation prevents CD8 transformation. These results explain how CD8 T cells maintain genome integrity in spite of their extensive division, and highlight the fundamental role of DDRs in the efficiency of CD8 immune responses.
Bridging the Timescales of Single-Cell and Population Dynamics
NASA Astrophysics Data System (ADS)
Jafarpour, Farshid; Wright, Charles S.; Gudjonson, Herman; Riebling, Jedidiah; Dawson, Emma; Lo, Klevin; Fiebig, Aretha; Crosson, Sean; Dinner, Aaron R.; Iyer-Biswas, Srividya
2018-04-01
How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to the replication-competent (stalked) stage of the Caulobacter crescentus life cycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For C. crescentus cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time and, thus, yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell-age distribution, and the quiescence timescale.
Analysis of cell division patterns in the Arabidopsis shoot apical meristem
Shapiro, Bruce E.; Tobin, Cory; Mjolsness, Eric; ...
2015-03-30
The stereotypic pattern of cell shapes in the Arabidopsis shoot apical meristem (SAM) suggests that strict rules govern the placement of new walls during cell division. When a cell in the SAM divides, a new wall is built that connects existing walls and divides the cytoplasm of the daughter cells. Because features that are determined by the placement of new walls such as cell size, shape, and number of neighbors are highly regular, rules must exist for maintaining such order. Here in this paper we present a quantitative model of these rules that incorporates different observed features of cell division.more » Each feature is incorporated into a "potential function" that contributes a single term to a total analog of potential energy. New cell walls are predicted to occur at locations where the potential function is minimized. Quantitative terms that represent the well-known historical rules of plant cell division, such as those given by Hofmeister, Errera, and Sachs are developed and evaluated against observed cell divisions in the epidermal layer (L1) of Arabidopsis thaliana SAM. The method is general enough to allow additional terms for nongeometric properties such as internal concentration gradients and mechanical tensile forces.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aggarwal, Pooja; Padmanabhan, Bhavna; Bhat, Abhay
2011-07-01
Highlights: {yields} TCP4 is a class II TCP transcription factor, that represses cell division in Arabidopsis. {yields} TCP4 expression in yeast retards cell division by blocking G1 {yields} S transition. {yields} Genome-wide expression studies and Western analysis reveals stabilization of cell cycle inhibitor Sic1, as possible mechanism. -- Abstract: The TCP transcription factors control important aspects of plant development. Members of class I TCP proteins promote cell cycle by regulating genes directly involved in cell proliferation. In contrast, members of class II TCP proteins repress cell division. While it has been postulated that class II proteins induce differentiation signal, theirmore » exact role on cell cycle has not been studied. Here, we report that TCP4, a class II TCP protein from Arabidopsis that repress cell proliferation in developing leaves, inhibits cell division by blocking G1 {yields} S transition in budding yeast. Cells expressing TCP4 protein with increased transcriptional activity fail to progress beyond G1 phase. By analyzing global transcriptional status of these cells, we show that expression of a number of cell cycle genes is altered. The possible mechanism of G1 {yields} S arrest is discussed.« less
Duranthon, Véronique
2018-01-01
ABSTRACT Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones. PMID:29567671
Diel Variations in Optical Properties of Micromonas pusilla, a Prasinophyte
NASA Technical Reports Server (NTRS)
DuRand, Michele D.; Green, Rebecca E.; Sosik, Heidi M.; Olson, Robert J.
2001-01-01
A laboratory experiment was conducted on cultures of Micromonas pusilla, a marine prasinophyte, to investigate how cell growth and division affect the optical properties over the light:dark cycle. Measurements were made of cell size and concentration, attenuation and absorption coefficients, flow cytometric light scattering (in forward and side directions), chlorophyll and carbon content. Refractive index was calculated using the anomalous diffraction approximation Cells were about 1.5 micrometers in diameter and exhibited phased division, with the major division burst occurring during the night. Typical diel variations were observed, with cells increasing in size and light scattering during the day as they photosynthesize and decreasing at night upon division. The cells were in ultradian growth, with more than one division per day, at a light level of 120 Mu-mol photons m/sq/sec. Since these cells are similar in size to small phytoplankton that are typically abundant in field samples, these results can be used in the interpretation of diel variations in light scattering in natural populations of phytoplankton.
Enrico, Paolo; Diana, Marco
2017-01-01
Over the last 20 years researchers have explored the postulated role of acetaldehyde (ACD) as a mediator of some of the actions of ethanol (EtOH) in the central nervous system (CNS). However, efforts have been hampered mainly by the difficulty of directly measuring in vivo EtOH and ACD levels in the CNS and thus, our knowledge is based on indirect evidences. Although technically challenging, the development of reliable methods for in vivo measurement of ACD and EtOH is of paramount importance to solve the " puzzle of acetaldehyde as a neuroactive agent. " In this short review we discuss the recent advances on brain EtOH pharmacokinetic and state-of-the-art available techniques that could be used for in vivo detect EtOH and ACD both non-invasively (magnetic resonance spectroscopy), and invasively (microdialysis and biosensors). Among the different in vivo sampling techniques described, particular emphasis is paid to the field of enzyme-based amperometric biosensors. Biosensors have gained much attention in recent years for their ability to online monitor biological signals in vivo , and several micro- and nano-structured devices have been successfully used for in vivo studies. Owing to their high temporal and spatial resolution, biosensors could provide the adequate technology for studying in vivo EtOH pharmacokinetic.
Furukawa, T; Manabe, S; Watanabe, T; Sehata, S; Sharyo, S; Okada, T; Mori, Y
1999-09-01
Hepatic P450 monooxygenase activities, which strongly influence the efficacy and/or toxicity of drugs, are known to fluctuate daily. We also know that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities fluctuate daily, with apparently high values during the dark period in male rats. However, there is little knowledge about the factors that regulate daily fluctuation of P450 monooxygenase activities. In the present study using rats, we induced lesions in the suprachiasmatic nucleus (SCN) of the brain, the known site of the body's internal clock, and examined the effects on the daily fluctuation of the ACD activities to clarify the relationship between the SCN and the daily fluctuation of P450 monooxygenase activities. In addition, adrenalectomy was performed to re-evaluate the influence of adrenal hormones on the P450 activities. Our results indicated that daily fluctuations of the hepatic ACD activities were completely eliminated in the SCN-lesioned rats. However, the ACD activities in the adrenalectomized rats showed apparent daily fluctuations with high values during the dark period and low values during the light period. Therefore, this study demonstrated that the daily fluctuation of the hepatic P450 monooxygenase activities in male rats is controlled by the SCN but remains unaffected by the adrenal hormones.
Kerkhoff, A D; Meintjes, G; Opie, J; Vogt, M; Jhilmeet, N; Wood, R; Lawn, S D
2016-02-01
Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration ⩿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.
Lemaire, Benny; Van Cauwenberghe, Jannick; Chimphango, Samson; Stirton, Charles; Honnay, Olivier; Smets, Erik; Muasya, A Muthama
2015-11-01
The goal of this work is to study the evolution and the degree of horizontal gene transfer (HGT) within rhizobial genera of both Alphaproteobacteria (Mesorhizobium, Rhizobium) and Betaproteobacteria (Burkholderia), originating from South African Fynbos legumes. By using a phylogenetic approach and comparing multiple chromosomal and symbiosis genes, we revealed conclusive evidence of high degrees of horizontal transfer of nodulation genes among closely related species of both groups of rhizobia, but also among species with distant genetic backgrounds (Rhizobium and Mesorhizobium), underscoring the importance of lateral transfer of symbiosis traits as an important evolutionary force among rhizobia of the Cape Fynbos biome. The extensive exchange of symbiosis genes in the Fynbos is in contrast with a lack of significant events of HGT among Burkholderia symbionts from the South American Cerrado and Caatinga biome. Furthermore, homologous recombination among selected housekeeping genes had a substantial impact on sequence evolution within Burkholderia and Mesorhizobium. Finally, phylogenetic analyses of the non-symbiosis acdS gene in Mesorhizobium, a gene often located on symbiosis islands, revealed distinct relationships compared to the chromosomal and symbiosis genes, suggesting a different evolutionary history and independent events of gene transfer. The observed events of HGT and incongruence between different genes necessitate caution in interpreting topologies from individual data types. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Wang, Xuefei; Mavrodi, Dmitri V; Ke, Linfeng; Mavrodi, Olga V; Yang, Mingming; Thomashow, Linda S; Zheng, Na; Weller, David M; Zhang, Jibin
2015-01-01
The aim of this study was to inventory the types of plant growth-promoting rhizobacteria (PGPR) present in the rhizosphere of plants grown in soils contaminated with heavy metals, recalcitrant organics, petroleum sewage or salinity in China. We screened 1223 isolates for antifungal activity and about 24% inhibited Rhizoctonia solani or Sclerotinia sclerotiorum. Twenty-four strains inhibitory to R. solani, Gaeumannomyces graminis var. tritici and/or S. sclerotiorum and representing the dominant morphotypes were assayed for PGPR activity. Seven strains contained phlD, prnD, pltC or phzF genes and produced the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin, pyoluteorin and phenazines respectively. Six strains contained acdS, which encodes 1-aminocyclopropane-1-carboxylic acid deaminase. Phylogenetic analysis of 16S rDNA and phlD, phzF and acdS genes demonstrated that some strains identified as Pseudomonas were similar to model PGPR strains Pseudomonas protegens Pf-5, Pseudomonas chlororaphis subsp. aureofaciens 30–84 and P. brassicacearum Q8r1-96. Pseudomonas protegens- and P. chlororaphis-like strains had the greatest biocontrol activity against Rhizoctonia root rot and take-all of wheat. Pseudomonas protegens and P. brassicacearum-like strains showed the greatest promotion of canola growth. Our results indicate that strains from contaminated soils are similar to well-described PGPR found in agricultural soils worldwide. Growth-promoting rhizobacteria in polluted soils PMID:25219642
Williams, Scott G
2006-03-01
To examine the impact of detection biases on three prostate cancer biochemical failure (bF) definitions in comparison with the existing American Society for Therapeutic Radiology and Oncology Consensus Definition (ACD). Three alternative bF definitions were tested against the ACD: three rises in prostate-specific antigen (PSA) level without backdating, nadir plus 2 ng/mL, and a threshold PSA level of >3 ng/mL, according to data from 1050 men. The mean time between PSA tests (MTBT), regularity of collection, and calendar year of analysis were examined in each bF definition. The MTBT produced a statistically significant difference in the derived hazard ratio for identification of bF in all definitions. The influence of test regularity was statistically significant beyond the median level of regularity in all definitions. The year of analysis impacted greatly on the ACD, whereas the three alternative definitions exhibited minor follow-up duration variations by comparison. The alternative definitions had reliable follow-up when the crude median time to censoring was at least 1.6 times greater than that of failure. Detection biases will always be a significant issue in defining bF. A number of alternative failure definitions have more predictable interactions with these biases than the existing ACD.
Footwear contact dermatitis from dimethyl fumarate.
Švecová, Danka; Šimaljakova, Maria; Doležalová, Anna
2013-07-01
Dimethyl fumarate (DMF) is an effective inhibitor of mold growth. In very low concentrations, DMF is a potent sensitizer that can cause severe allergic contact dermatitis (ACD). It has been identified as the agent responsible for furniture contact dermatitis in Europe. The aim of this study was to evaluate patients in Slovakia with footwear ACD associated with DMF, with regard to clinical manifestations, patch test results, and results of chemical analysis of their footwear. Nine patients with suspected footwear contact dermatitis underwent patch testing with the following allergens: samples of their own footwear, commercial DMF, the European baseline, shoe screening, textile and leather dye screening, and industrial biocides series. The results were recorded according to international guidelines. The content of DMF in footwear and anti-mold sachets was analyzed using gas chromatography and mass spectrometry. Acute ACD was observed in nine Caucasian female patients. All patients developed delayed sensitization, as demonstrated by positive patch testing using textile footwear lining. Seven patients were patch tested with 0.1% DMF, and all seven were positive. Chemical analysis of available footwear showed that DMF was present in very high concentrations (25-80 mg/Kg). Dimethyl fumarate is a new footwear allergen and was responsible for severe ACD in our patients. To avoid an increase in the number of cases, the already approved European preventive measures should be accepted and commonly employed. © 2013 The International Society of Dermatology.
Lee, Chang Jae; Chung, Tae Nyoung; Bae, Jinkun; Kim, Eui Chung; Choi, Sung Wook; Kim, Ok Jun
2015-03-01
Current guidelines for cardiopulmonary resuscitation recommend chest compressions (CC) during 50% of the duty cycle (DC) in part because of the ease with which individuals may learn to achieve it with practice. However, no consideration has been given to a possible interaction between DC and depth of CC, which has been the subject of recent study. Our aim was to determine if 50% DC is inappropriate to achieve sufficient chest compression depth for female and light rescuers. Previously collected CC data, performed by senior medical students guided by metronome sounds with various down-stroke patterns and rates, were included in the analysis. Multiple linear regression analysis was performed to determine the association between average compression depth (ACD) with average compression rate (ACR), DC, and physical characteristics of the performers. Expected ACD was calculated for various settings. DC, ACR, body weight, male sex, and self-assessed physical strength were significantly associated with ACD in multivariate analysis. Based on our calculations, with 50% of DC, only men with ACR of 140/min or faster or body weight over 74 kg with ACR of 120/min can achieve sufficient ACD. A shorter DC is independently correlated with deeper CC during simulated cardiopulmonary resuscitation. The optimal DC recommended in current guidelines may be inappropriate for achieving sufficient CD, especially for female or lighter-weight rescuers.
The Distinct Biometric Features of High Myopia Compared to Moderate Myopia.
Chung, Hye Jin; Park, Chan Kee
2016-12-01
To evaluate changes in biometric parameters in myopic eyes. 412 eyes of 412 young myopic patients underwent ophthalmic examinations including assessments of refractive error, axial length (AL), anterior chamber depth (ACD), and central corneal thickness (CCT). By using spectral domain optical coherence tomography (SD-OCT), peripapillary retinal nerve fiber layer (pRNFL) thickness was measured. Subjects were divided into two groups: a moderate-myope group (-6 diopters (D) or more) and a high-myope group (less than -6 D). The relationships among ocular biometric parameters including pRNFL thickness, AL, ACD, and CCT were calculated for each group. In the moderate-myopia group, the anterior chamber deepened as AL increased (Pearson's coefficient = 0.346, p < 0.01). However, in the high-myopia group, ACD did not correlate with AL (Pearson's r = 0.065, p = 0.383). Average pRNFL thickness was also more related to SE than AL in highly myopic eyes. In highly myopic eyes, ACD did not increase as AL increased. pRNFL thickness was more related to SE than to AL. That might be due to the uneven elongation of anterior and posterior portions of the eyeball and the discrepancy between distance from the cornea to the fovea and distance from the cornea to the bottom of the eyeball as axial eye elongation. Interpretation of ocular biometric parameter in highly myopic eyes should consider these differences.
Ong, Lee-Ling S; Xinghua Zhang; Kundukad, Binu; Dauwels, Justin; Doyle, Patrick; Asada, H Harry
2016-08-01
An approach to automatically detect bacteria division with temporal models is presented. To understand how bacteria migrate and proliferate to form complex multicellular behaviours such as biofilms, it is desirable to track individual bacteria and detect cell division events. Unlike eukaryotic cells, prokaryotic cells such as bacteria lack distinctive features, causing bacteria division difficult to detect in a single image frame. Furthermore, bacteria may detach, migrate close to other bacteria and may orientate themselves at an angle to the horizontal plane. Our system trains a hidden conditional random field (HCRF) model from tracked and aligned bacteria division sequences. The HCRF model classifies a set of image frames as division or otherwise. The performance of our HCRF model is compared with a Hidden Markov Model (HMM). The results show that a HCRF classifier outperforms a HMM classifier. From 2D bright field microscopy data, it is a challenge to separate individual bacteria and associate observations to tracks. Automatic detection of sequences with bacteria division will improve tracking accuracy.
ERIC Educational Resources Information Center
Oztap, Haydar; Ozay, Esra; Oztap, Fulya
2003-01-01
This study examines the difficulties biology teachers face when teaching cell division in the secondary schools of the central part of the Erzurum province in Turkey. During this research, a questionnaire was distributed to a total of 36 secondary school biology teachers. Findings of the study indicate biology teachers perceive cell division as…
Phytoplankton division rates in light-limited environments: two adaptations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rivkin, R.B.; Voytek, M.A.; Seliger, H.H.
1982-02-26
Red tide-forming dinoflagellates maximize cell numbers during periods of low light intensities in two ways. For short-term exposures to suboptimal light intensities such as might occur during recirculation in frontal convergences, cell division rates can be maintained at the expense of stored carbon for up to two generation times. During longer periods, corresponding to subsurface transport below a pycnocline, cell division rates eventually decrease as a portion of the fixed carbon is diverted to replenishing stored carbon. As a result, maximum rates of cell division can be resumed rapidly upon advection into surface waters where light intensities are optimal formore » growth.« less
Piekarska-Stachowiak, Anna; Nakielski, Jerzy
2013-12-01
In contrast to seed plants, the roots of most ferns have a single apical cell which is the ultimate source of all cells in the root. The apical cell has a tetrahedral shape and divides asymmetrically. The root cap derives from the distal division face, while merophytes derived from three proximal division faces contribute to the root proper. The merophytes are produced sequentially forming three sectors along a helix around the root axis. During development, they divide and differentiate in a predictable pattern. Such growth causes cell pattern of the root apex to be remarkably regular and self-perpetuating. The nature of this regularity remains unknown. This paper shows the 2D simulation model for growth of the root apex with the apical cell in application to Azolla pinnata. The field of growth rates of the organ, prescribed by the model, is of a tensor type (symplastic growth) and cells divide taking principal growth directions into account. The simulations show how the cell pattern in a longitudinal section of the apex develops in time. The virtual root apex grows realistically and its cell pattern is similar to that observed in anatomical sections. The simulations indicate that the cell pattern regularity results from cell divisions which are oriented with respect to principal growth directions. Such divisions are essential for maintenance of peri-anticlinal arrangement of cell walls and coordinated growth of merophytes during the development. The highly specific division program that takes place in merophytes prior to differentiation seems to be regulated at the cellular level.
Ploidy-Dependent Unreductional Meiotic Cell Division in Polyploid Wheat
USDA-ARS?s Scientific Manuscript database
Meiosis includes one round of DNA replication and two successive nuclear divisions, i.e. meiosis I (reductional) and meiosis II (equational). This specialized cell division reduces chromosomes in half and generates haploid gametes in sexual reproduction of eukaryotes. It ensures faithful transmiss...
Li, Yuwei; Li, Ang; Junge, Jason; Bronner, Marianne
2017-10-10
Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Here we examine the linkage between these processes in chick limb cartilage. By combining retroviral-based multicolor clonal analysis with live imaging, the results show that single chondrocyte precursors can generate both single-column and multi-column clones through oriented division followed by cell rearrangements. Focusing on single column formation, we show that this stereotypical tissue architecture is established by a pivot-like process between sister cells. After mediolateral cell division, N-cadherin is enriched in the post-cleavage furrow; then one cell pivots around the other, resulting in stacking into a column. Perturbation analyses demonstrate that planar cell polarity signaling enables cells to pivot in the direction of limb elongation via this N-cadherin-mediated coupling. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton.
Li, Yuwei; Li, Ang; Junge, Jason
2017-01-01
Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Here we examine the linkage between these processes in chick limb cartilage. By combining retroviral-based multicolor clonal analysis with live imaging, the results show that single chondrocyte precursors can generate both single-column and multi-column clones through oriented division followed by cell rearrangements. Focusing on single column formation, we show that this stereotypical tissue architecture is established by a pivot-like process between sister cells. After mediolateral cell division, N-cadherin is enriched in the post-cleavage furrow; then one cell pivots around the other, resulting in stacking into a column. Perturbation analyses demonstrate that planar cell polarity signaling enables cells to pivot in the direction of limb elongation via this N-cadherin-mediated coupling. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton. PMID:28994649
Optimizing homeostatic cell renewal in hierarchical tissues
Fider, Nicole A.
2018-01-01
In order to maintain homeostasis, mature cells removed from the top compartment of hierarchical tissues have to be replenished by means of differentiation and self-renewal events happening in the more primitive compartments. As each cell division is associated with a risk of mutation, cell division patterns have to be optimized, in order to minimize or delay the risk of malignancy generation. Here we study this optimization problem, focusing on the role of division tree length, that is, the number of layers of cells activated in response to the loss of terminally differentiated cells, which is related to the balance between differentiation and self-renewal events in the compartments. Using both analytical methods and stochastic simulations in a metapopulation-style model, we find that shorter division trees are advantageous if the objective is to minimize the total number of one-hit mutants in the cell population. Longer division trees on the other hand minimize the accumulation of two-hit mutants, which is a more likely evolutionary goal given the key role played by tumor suppressor genes in cancer initiation. While division tree length is the most important property determining mutant accumulation, we also find that increasing the size of primitive compartments helps to delay two-hit mutant generation. PMID:29447149
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nathan, P.D.
Experiments are described that examine the role of penicillin-binding proteins (PBPs) in the regulation of cell division in Caulobacter crescentus; and the spatial localization of methyl-accepting chemotaxis proteins (MCPs) in C. crescentus swarmer and predivisional cells. In the analysis of PBP function, in vivo and in vitro assays are used to directly label C. crescentus PBPs with (/sup 3/H) penicillin G in wild type strain CB15, in a series of conditional cell division mutants and in new temperature sensitive cephalosporin C resistant mutants PC8002 and PC8003. 14 PBPs are characterized and a high molecular weight PBP (PBP 1B) that ismore » required for cell division is identified. PBP 1B competes for ..beta..-lactams that induce filament formation and may be a high affinity binding protein. A second high molecular weight PBP (PBP 1C) is also associated with defective cell division. The examination of PBP patterns in synchronous swarmer cells reveals that the in vivo activity of PBP 1B and PBP 1C increases at the time that the cell division pathway is initiated. None of the PBPs, however, appear to be differentially localized in the C. crescentus cell. In the analysis of MCP localization, in vivo and in vitro assays are used to directly label C. crescentus MCPs with methyl-/sup 3/H. MCPs are examined in flagellated and non-flagellated vesicles prepared from cells by immunoaffinity chromatography.« less
Fock, R.A.; Vinolo, M.A.R.; Blatt, S.L.; Borelli, P.
2012-01-01
The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 × 104 cells/mL) compared to control (69.6 ± 7.1 × 104 cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h−1·mL−1), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h−1·mL−1, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL, respectively, P ≤ 0.05). The reduced expression of IL-1β, together with the lower number of leukocytes in the central and peripheral compartments, different leukocyte kinetics, and reduced leukocyte migration capacity are factors that interfere with the capacity to mount an adequate immune response, being partly responsible for the immunodeficiency observed in PEM. PMID:22983177
Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C
2011-11-01
Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.
Anaemia in rheumatoid arthritis: can we afford to ignore it?
Bloxham, E; Vagadia, V; Scott, K; Francis, G; Saravanan, V; Heycock, C; Rynne, M; Hamilton, J; Kelly, C A
2011-09-01
INTRODUCTION Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications. METHODS The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded. RESULTS Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B(12) deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism. CONCLUSIONS Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.
A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom.
Lye, Jessica; Kenny, John; Lehmann, Joerg; Dunn, Leon; Kron, Tomas; Alves, Andrew; Cole, Andrew; Williams, Ivan
2014-10-01
The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantoms are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%-8%. The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.
Williams, Scott G; Pickles, Tom; Kestin, Larry; Potters, Louis; Fearn, Paul; Smith, Ryan; Pratt, Gary
2006-08-01
To evaluate the interobserver variation of four electronic biochemical failure (bF) calculators using three bF definitions. The data of 1200 men were analyzed using the electronic bF calculators of four institutions. Three bF definitions were examined for their concordance of bF identification across the centers: the American Society for Therapeutic Radiology and Oncology consensus definition (ACD), the lowest prostate-specific antigen (PSA) level to date plus 2 ng/mL (L2), and a threshold of 3 ng/mL (T3). Unanimous agreement regarding bF status using the ACD, L2, and T3 definitions occurred in 87.3%, 96.4%, and 92.7% of cases, respectively. Using the ACD, 63% of the variation was from one institution, which allowed the bF status to be reversed if a PSA decline was seen after bF (PSA "bounce"). A total of 270 men had an ACD bF time variation of >2 months across the calculators, and the 5-year freedom from bF rate was 49.8-60.9%. The L2 definition had a 20.5% rate of calculated bF times; which varied by >2 months (median, 6.4; range, 2.1-75.6) and a corresponding 5-year freedom from bF rate of 55.9-61.0%. The T3 definition had a 2.0% range in the 5-year freedom from bF. Fifteen definition interpretation variations were identified. Reported bF results vary not only because of bF definition differences, but because of variations in how those definitions are written into computer-based calculators, with multiple interpretations most prevalent for the ACD. An algorithm to avoid misinterpretations is proposed for the L2 definition. A verification system to guarantee consistent electronic bF results requires development.
Acevedo, María B.; D'Aloisio, Génesis; Haymal, Olga B.; Molina, Juan C.
2017-01-01
Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the immature organism and its subsequent affinity for ethanol operationalized through self-administration procedures. PMID:28377702
Acevedo, María B; D'Aloisio, Génesis; Haymal, Olga B; Molina, Juan C
2017-01-01
Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the immature organism and its subsequent affinity for ethanol operationalized through self-administration procedures.
Kuršumović, Adisa; Rath, Stefan A
2018-01-01
Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.
Ohsawa, Masaki; Okamura, Tomonori; Ogasawara, Kuniaki; Ogawa, Akira; Fujioka, Tomoaki; Tanno, Kozo; Yonekura, Yuki; Omama, Shinichi; Turin, Tanvir Chowdhury; Itai, Kazuyoshi; Ishibashi, Yasuhiro; Morino, Yoshihiro; Itoh, Tomonori; Miyamatsu, Naomi; Onoda, Toshiyuki; Kuribayashi, Toru; Makita, Shinji; Yoshida, Yuki; Nakamura, Motoyuki; Tanaka, Fumitaka; Ohta, Mutsuko; Sakata, Kiyomi; Okayama, Akira
2015-04-01
The relative and absolute risks of outcomes other than all-cause death (ACD) attributable to atrial fibrillation (AF) stratified age have not been sufficiently investigated. A prospective study of 23,634 community dwellers aged 40 years or older without organic cardiovascular disease (AF=335, non-AF=23,299) was conducted. Multivariate-adjusted rates, rate ratios (RRs) and excess deaths (EDs) for ACD, cardiovascular death (CVD) and non-cardiovascular death (non-CVD), and sex- and age-adjusted RR and ED in middle-aged (40 to 69) and elderly (70 years or older) for ACD, CVD, non-CVD, sudden cardiac death (SCD), stroke-related death (Str-D), neoplasm-related death (NPD), and infection-related death (IFD) attributable to AF were estimated using Poisson regression. Multivariate-adjusted analysis revealed that AF significantly increased the risk of ACD (RR [95% confidence interval]:1.70 [1.23-2.95]) and CVD (3.86 [2.38-6.27]), but not non-CVD. Age-stratified analysis revealed that AF increased the risk of Str-D in middle-aged (14.5 [4.77-44.3]) and elderly individuals (4.92 [1.91-12.7]), SCD in elderly individuals (3.21 [1.37-7.51]), and might increase the risk of IFD in elderly individuals (2.02 [0.80-4.65], p=0.098). The RR of CVD was higher in middle-aged versus elderly individuals (RRs, 6.19 vs. 3.57) but the absolute risk difference was larger in elderly individuals (EDs: 7.6 vs. 3.0 per 1000 person-years). Larger absolute risk differences for ACD and CVD attributable to AF among elderly people indicate that the absolute burden of AF is higher in elderly versus middle-aged people despite the relatively small RR. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Division of labour in the yeast: Saccharomyces cerevisiae.
Wloch-Salamon, Dominika M; Fisher, Roberta M; Regenberg, Birgitte
2017-10-01
Division of labour between different specialized cell types is a central part of how we describe complexity in multicellular organisms. However, it is increasingly being recognized that division of labour also plays an important role in the lives of predominantly unicellular organisms. Saccharomyces cerevisiae displays several phenotypes that could be considered a division of labour, including quiescence, apoptosis and biofilm formation, but they have not been explicitly treated as such. We discuss each of these examples, using a definition of division of labour that involves phenotypic variation between cells within a population, cooperation between cells performing different tasks and maximization of the inclusive fitness of all cells involved. We then propose future research directions and possible experimental tests using S. cerevisiae as a model organism for understanding the genetic mechanisms and selective pressures that can lead to the evolution of the very first stages of a division of labour. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Tulina, Natalia M; Chen, Wen-Feng; Chen, Jung Hsuan; Sowcik, Mallory; Sehgal, Amita
2014-02-25
Adult stem cells maintain tissue integrity and function by renewing cellular content of the organism through regulated mitotic divisions. Previous studies showed that stem cell activity is affected by local, systemic, and environmental cues. Here, we explore a role of environmental day-night cycles in modulating cell cycle progression in populations of adult stem cells. Using a classic stem cell system, the Drosophila spermatogonial stem cell niche, we reveal daily rhythms in division frequencies of germ-line and somatic stem cells that act cooperatively to produce male gametes. We also examine whether behavioral sleep-wake cycles, which are driven by the environmental day-night cycles, regulate stem cell function. We find that flies lacking the sleep-promoting factor Sleepless, which maintains normal sleep in Drosophila, have increased germ-line stem cell (GSC) division rates, and this effect is mediated, in part, through a GABAergic signaling pathway. We suggest that alterations in sleep can influence the daily dynamics of GSC divisions.
Adebonojo, Festus O.
1975-01-01
In an effort to test the adipose hyperplasia theory of obesity in humans, adipose cells, derived from anterior abdominal walls of human infants and children, were grown in synthetic medium (McCoy's 5A Medium) supplemented with 20% fetal calf serum. Adipose cells which became delipidinized in culture were found to be capable of division and the rate and number of cell divisions was age dependent. Cells of infants under 1 yr of age and cells derived from early adolescent children divided to varying degrees in culture. Adipose cells from children aged 1-10 yr showed no cell division. Cell division was never observed in a lipid-laden adipocyte. Measurements of cell diameter showed that after the first year of life, cell size increased progressively with age. During the first year adipose cell size appeared to reflect the rapid hyperplasia of the first 3 mo, reaching smallest size at 3-12 mo but increasing thereafter. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:124114
Higgins, M. L.; Daneo-Moore, L.; Boothby, D.; Shockman, G. D.
1974-01-01
Selective inhibition of protein synthesis in Streptococcus faecalis (ATCC 9790) was accompanied by a rapid and severe inhibition of cell division and a reduction of enlargement of cellular surface area. Continued synthesis of cell wall polymers resulted in rapid thickening of the wall to an extent not seen in exponential-phase populations. Thus, the normal direction of wall growth was changed from a preferential feeding out of new wall surface to that of thickening existing cell surfaces. However, the overall manner in which the wall thickened, from nascent septa toward polar regions, was the same in both exponential-phase and inhibited populations. In contrast, selective inhibition of deoxyribonucleic acid (DNA) synthesis using mitomycin C was accompanied by an increase in cellular surface area and by division of about 80% of the cells in random populations. Little or no wall thickening was observed until the synthesis of macromolecules other than DNA was impaired and further cell division ceased. Concomitant inhibition of both DNA and protein synthesis inhibited cell division but permitted an increase in average cell volume. In such doubly inhibited cells, walls thickened less than in cells inhibited for protein synthesis only. On the basis of the results obtained, a model for cell surface enlargement and cell division is presented. The model proposes that: (i) each wall enlargement site is influenced by an individual chromosome replication cycle; (ii) during chromosome replication peripheral surface enlargement would be favored over thickening (or septation); (iii) a signal associated with chromosome termination would favor thickening (and septation) at the expense of surface enlargement; and (iv) a factor or signal related to protein synthesis would be required for one or more of the near terminal stages of cell division or cell separation, or both. Images PMID:4133352
Legal and ethical issues associated with Advance Care Directives in an Australian context.
Denniss, D L
2016-12-01
The need for appropriate mechanisms guiding end-of-life care is increasingly vital. This commentary compares the use of Advance Care Directives (ACD) in New South Wales and South Australia in order to highlight the inconsistency in Australian legislation, before exploring common problems, legal concerns and ethical issues associated with their application in an adult population. The benefits and detriments of statutory legislation for ACD are also evaluated. © 2016 Royal Australasian College of Physicians.
Role of asymmetric cell division in lifespan control in Saccharomyces cerevisiae
Higuchi-Sanabria, Ryo; Pernice, Wolfgang M A; Vevea, Jason D; Alessi Wolken, Dana M; Boldogh, Istvan R; Pon, Liza A
2014-01-01
Aging determinants are asymmetrically distributed during cell division in S. cerevisiae, which leads to production of an immaculate, age-free daughter cell. During this process, damaged components are sequestered and retained in the mother cell, and higher functioning organelles and rejuvenating factors are transported to and/or enriched in the bud. Here, we will describe the key quality control mechanisms in budding yeast that contribute to asymmetric cell division of aging determinants including mitochondria, endoplasmic reticulum (ER), vacuoles, extrachromosomal rDNA circles (ERCs), and protein aggregates. PMID:25263578
Influence of Th2 cells on hair cycle/growth after repeated cutaneous application of hapten.
Sugita, K; Nomura, T; Ikenouchi-Sugita, A; Ito, T; Nakamura, M; Miyachi, Y; Tokura, Y; Kabashima, K
2014-03-01
Exposure to contact allergens in order to produce allergic contact dermatitis (ACD) seems to induce hair cycle/growth, but the mechanism of this remains unclear. In the current study, we investigated this mechanism and found that repeated application of hapten induced production of interleukin (IL)-4 in lymph-node immune cells. In addition, hair growth was induced in mice after the adoptive transfer of T-helper (Th)2 cells that had been purified from mice exposed to repeated cutaneous application of hapten. These findings lead us to speculate that Th2 cells that are repeatedly hapten-sensitized are recruited to hapten-challenged skin areas, and thus stimulate the production of IL-4 in the vicinity of the hair follicles, which influences hair cycle/growth. Our results may provide fundamental insights into the mechanism of contact hypersensitivity-induced hair cycle/growth. © 2013 British Association of Dermatologists.
Cell lineages of the embryo of the nematode Caenorhabditis elegans.
Deppe, U; Schierenberg, E; Cole, T; Krieg, C; Schmitt, D; Yoder, B; von Ehrenstein, G
1978-01-01
Embryogenesis of the free-living soil nematode Caenorhabditis elegans produces a juvenile having about 550 cells at hatching. We have determined the lineages of 182 cells by tracing the divisions of individual cells in living embryos. An invariant pattern of cleavage divisions of the egg generates a set of stem cells. These stem cells are the founders of six stem cell lineages. Each lineage has its own clock--i.e., an autonomous rhythm of synchronous cell divisions. The rhythms are maintained in spite of extensive cellular rearrangement. The rate and the orientation of the cell divisions of the cell lineages are essentially invariant among individuals. Thus, the destiny of cells seems to depend primarily on their lineage history. The anterior position of the site of origin of the stem cells in the egg relates to the rate of the cell cycle clock, suggesting intracellular preprogramming of the uncleaved egg. We used a technique that allows normal embryogenesis, from the fertilized egg to hatching, outside the parent under a cover glass. Embryogenesis was followed microscopically with Nomarski interference optics and high-resolution video recording.
Helicobacter pylori shows asymmetric and polar cell divisome assembly associated with DNA replisome.
Kamran, Mohammad; Dubey, Priyanka; Verma, Vijay; Dasgupta, Santanu; Dhar, Suman K
2018-05-09
DNA replication and cell division are two fundamental processes in the life cycle of a cell. The majority of prokaryotic cells undergo division by means of binary fission in coordination with replication of the genome. Both processes, but especially their coordination, are poorly understood in Helicobacter pylori. Here, we studied the cell divisome assembly and the subsequent processes of membrane and peptidoglycan synthesis in the bacterium. To our surprise, we found the cell divisome assembly to be polar, which was well-corroborated by the asymmetric membrane and peptidoglycan synthesis at the poles. The divisome components showed its assembly to be synchronous with that of the replisome and the two remained associated throughout the cell cycle, demonstrating a tight coordination among chromosome replication, segregation and cell division in H. pylori. To our knowledge, this is the first report where both DNA replication and cell division along with their possible association have been demonstrated for this pathogenic bacterium. © 2018 Federation of European Biochemical Societies.
The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression.
Ewald, Jennifer C; Kuehne, Andreas; Zamboni, Nicola; Skotheim, Jan M
2016-05-19
Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. Copyright © 2016 Elsevier Inc. All rights reserved.
Moving with the flow: what transport laws reveal about cell division and expansion.
Silk, Wendy Kuhn
2006-01-01
This material was presented as a keynote talk for the symposium, "Crosstalk between cell division and expansion," organized by G.T.S. Beemster and H. Tsukaya at the International Botanical Congress, Vienna in July, 2005. The review focuses on the utility of continuity equations to understand relationships among cell size, division and expansion; insights from Lagrangian or cell-specific descriptions of developmental variables; and a growth-diffusion equation to show effects of root growth zones on the surrounding soil.
Actinomadura algeriensis sp. nov., an actinobacterium isolated from Saharan soil.
Lahoum, Abdelhadi; Bouras, Noureddine; Mathieu, Florence; Schumann, Peter; Spröer, Cathrin; Klenk, Hans-Peter; Sabaou, Nasserdine
2016-01-01
During the course of a screening programme for new taxa of actinobacteria, a strain designated ACD1(T), was isolated from a Saharan soil in the Hoggar region (Algeria). The taxonomic position of this strain was determined using a polyphasic taxonomic approach. The strain was observed to form extensively branched, non-fragmenting substrate mycelium, and aerial mycelium with straight to flexuous, hooked and irregular spirals (1-2 turns) forming short chains of spores. The diamino acid present in the cell wall is meso-diaminopimelic acid. Galactose, glucose, madurose, mannose and ribose occur in whole-cell hydrolysates. The diagnostic phospholipids detected were diphosphatidylglycerol and phosphatidylinositol. The major menaquinones were identified as MK-9 (H4) and MK-9 (H2). The major fatty acids were found to be C16:0, C18:1 cis9, iso-C16:0 and 10-methyl C18:0. Phylogenetic analysis based on the 16S rRNA gene showed that the strain belongs to the genus Actinomadura, and is closely related to Actinomadura sediminis DSM 45500(T) (98.5 % similarity) and Actinomadura cremea subsp. cremea DSM 43676(T) (98.3 % similarity). However, DNA-DNA hybridization revealed only 48.0 % relatedness with A. sediminis DSM 45500(T) and 33.2 % relatedness with A. cremea subsp. cremea DSM 43676(T). The combined phenotypic and genotypic data showed that the strain represents a novel species of the genus Actinomadura, for which the name Actinomadura algeriensis sp. nov. is proposed, with the type strain ACD1(T) (= DSM 46744(T) = CECT 8841(T)).
Asymmetric T lymphocyte division in the initiation of adaptive immune responses.
Chang, John T; Palanivel, Vikram R; Kinjyo, Ichiko; Schambach, Felix; Intlekofer, Andrew M; Banerjee, Arnob; Longworth, Sarah A; Vinup, Kristine E; Mrass, Paul; Oliaro, Jane; Killeen, Nigel; Orange, Jordan S; Russell, Sarah M; Weninger, Wolfgang; Reiner, Steven L
2007-03-23
A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.
Activity and Accumulation of Cell Division-Promoting Phenolics in Tobacco Tissue Cultures 1
Teutonico, Rita A.; Dudley, Matthew W.; Orr, John D.; Lynn, David G.; Binns, Andrew N.
1991-01-01
Dehydrodiconiferyl alcohol glucosides (DCGs) are derivatives of the phenylpropanoid pathway that have been isolated from Catharansus roseus L. (Vinca rosea) crown gall tumors. Fractions containing purified DCGs have been shown previously to promote the growth of cytokinin-requiring tissues of tobacco in the absence of exogenous cytokinins. In this study, we utilized synthetic DCG isomers to confirm the cell division-promoting activity of DCG isomers A and B and show that they neither promote shoot meristem initiation on Nicotiana tabacum L., cv Havana 425, leaf explants nor induce betacyanin synthesis in amaranth seedlings. Analysis of cultured tobacco pith tissue demonstrated that DCG accumulation was stimulated by cytokinin treatment and correlated with cytokinin-induced cell division. Thus, the accumulation of metabolites that could replace cytokinin in cell division bioassays is stimulated by cytokinins. These data support the model that DCGs are a component of a cytokinin-mediated regulatory circuit controlling cell division. ImagesFigure 2 PMID:16668384
NASA Astrophysics Data System (ADS)
Manuse, Sylvie; Jean, Nicolas L.; Guinot, Mégane; Lavergne, Jean-Pierre; Laguri, Cédric; Bougault, Catherine M.; Vannieuwenhze, Michael S.; Grangeasse, Christophe; Simorre, Jean-Pierre
2016-06-01
Accurate placement of the bacterial division site is a prerequisite for the generation of two viable and identical daughter cells. In Streptococcus pneumoniae, the positive regulatory mechanism involving the membrane protein MapZ positions precisely the conserved cell division protein FtsZ at the cell centre. Here we characterize the structure of the extracellular domain of MapZ and show that it displays a bi-modular structure composed of two subdomains separated by a flexible serine-rich linker. We further demonstrate in vivo that the N-terminal subdomain serves as a pedestal for the C-terminal subdomain, which determines the ability of MapZ to mark the division site. The C-terminal subdomain displays a patch of conserved amino acids and we show that this patch defines a structural motif crucial for MapZ function. Altogether, this structure-function analysis of MapZ provides the first molecular characterization of a positive regulatory process of bacterial cell division.
Patch Testing in Patients with Suspected Footwear Dermatitis: A Retrospective Study.
Garg, Taru; Agarwal, Soumya; Rana, Shiwangi; Chander, Ram
2017-01-01
Footwear dermatitis represents a common but often undiagnosed or misdiagnosed condition. Patch testing aids in its confirmation and identification of the offending allergen. This study aimed to find the frequency of positive patch test reactions in cases with suspected allergic contact dermatitis (ACD) to footwear, as well as the common responsible allergens. This is a retrospective record based study of 37 patients, with suspected ACD to footwear, who underwent patch testing with Indian standard series and Indian footwear series from July 2012 to July 2015. The majority of patients (45.94%) belonged to the age group of 20-40 years. Dorsal aspects of feet (81.08%) and soles (18.92%) were the common sites involved. Patch test was positive in 18.92% patients. The most common causative allergens were hydroquinone monobenzylether (8.11%) and 4-aminoazobenzene (5.41%). Common chemicals implicated in ACD were rubber, rubber additives, and dyes. The principal culprit allergens were hydroquinone monobenzylether and 4-aminoazobenzene.
Acetaldehyde involvement in ethanol's postabsortive effects during early ontogeny.
March, Samanta M; Abate, P; Molina, Juan C
2013-01-01
Clinical and biomedical studies sustains the notion that early ontogeny is a vulnerable window to the impact of alcohol. Experiences with the drug during these stages increase latter disposition to prefer, use or abuse ethanol. This period of enhanced sensitivity to ethanol is accompanied by a high rate of activity in the central catalase system, which metabolizes ethanol in the brain. Acetaldehyde (ACD), the first oxidation product of ethanol, has been found to share many neurobehavioral effects with the drug. Cumulative evidence supports this notion in models employing adults. Nevertheless very few studies have been conducted to analyze the role of ACD in ethanol postabsorptive effects, in newborns or infant rats. In this work we review recent experimental literature that syndicates ACD as a mediator agent of reinforcing aspects of ethanol, during early ontogenetic stages. We also show a meta-analytical correlational approach that proposes how differences in the activity of brain catalase across ontogeny, could be modulating patterns of ethanol consumption.
[Regulators in access to anticancer drugs in Canada].
Côté, André; Keating, Bernard; Parent, Marc; Simard, Guy
2015-01-01
Based exclusively on drugs approved by provincial public health insurance systems, many authors have reported significant variability in terms of access to anticancer drugs (ACD) among Canadian citizens, raising problems of equal access to these drugs.In this paper, we emphasize that the mere presence on the list of public drug plans cannot be considered to be a sufficient indicator to determine the real availability of anticancer drugs (ACD) for the patient. We describe and compare four sets of regulators defined in each province and determine their effects on the accessibility of ACD for patients in each province. The term regulator comprises the conditions which must be observed for access via the public health insurance system as well as the rules (strategies) decided by the third-party payer for the management of these conditions.The results of our analyses lead to the conclusion that there is indeed a variation between provinces in terms of access to drugs financed by public funds, but that this variability primarily impacts less important treatments.
Are There Really Animals Like That? No Cell Division.
ERIC Educational Resources Information Center
Blackwelder, R. E.; Garoian, G. S.
1984-01-01
Provides examples of animals in which growth occurs without cell division. Indicates that this phenomenon (called cell constancy or eutely) is an oddity of development that has arisen independently in several animal groups. (JN)
Hayden, Patrick; Singh, Mandip
2013-01-01
Purpose The aim of the current study was to investigate the percutaneous permeation pathways of cell penetrating peptide modified lipid nanoparticles and oleic acid modified polymeric nanoparticles. Methods Confocal microscopy was performed on skin cultures (EpiDermFT™) for modified and un-modified nanoparticles. Differential stripping was performed following in vitro skin permeation of Ibuprofen (Ibu) encapsulated nanoparticles to estimate Ibu levels in different skin layers and receiver compartment. The hair follicles (HF) were blocked and in vitro skin permeation of nanoparticles was then compared with unblocked HF. The surface modified nanoparticles were investigated for response on allergic contact dermatitis (ACD). Results Surface modified nanoparticles showed a significant higher (p < 0.05) in fluorescence in EpiDermFT™ cultures compared to controls. The HF play less than 5% role in total nanoparticle permeation into the skin. The Ibu levels were significantly high (p<0.05) for surface modified nanoparticles compared to controls. The Ibu levels in skin and receiver compartment were not significantly different when HF were open or closed. Modified nanoparticles showed significant improvement in treatment of ACD compared to solution. Conclusions Our studies demonstrate that increased skin permeation of surface modified nanoparticles is not only dependent on a follicular pathway but also occur through non-follicular pathway(s). PMID:23187866
Berres, Marie-Luise; Merad, Miriam; Allen, Carl E.
2016-01-01
Summary Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, is characterized by the accumulation of CD1A+/CD207+ mononuclear phagocytes within granulomatous lesions that can affect nearly all organ systems. Historically, LCH has been presumed to arise from transformed or pathologically activated epidermal dendritic cells called Langerhans cells. However, new evidence supports a model in which LCH occurs as a consequence of a misguided differentiation programme of myeloid dendritic cell precursors. Genetic, molecular and functional data implicate activation of the ERK signalling pathway at critical stages in myeloid differentiation as an essential and universal driver of LCH pathology. Based on these findings, we propose that LCH should be re-defined as an inflammatory myeloid neoplasia. Increased understanding of LCH pathogenesis will provide opportunities to optimize and personalize therapy through improved risk-stratification, targeted therapy and assessment of therapy response based on specific molecular features and origin of the pathological myeloid cells. PMID:25430560
Hendricks, Deborah W; Balfour, Henry H; Dunmire, Samantha K; Schmeling, David O; Hogquist, Kristin A; Lanier, Lewis L
2014-05-15
CMV induces the expansion of a unique subset of human NK cells expressing high levels of the activating CD94-NKG2C receptor that persist after control of the infection. We investigated whether this subset is CMV specific or is also responsive to acute infection with EBV. We describe a longitudinal study of CMV(-) and CMV(+) students who were acutely infected with EBV. The NKG2C(hi) NK subset was not expanded by EBV infection. However, EBV infection caused a decrease in the absolute number of immature CD56(bright)CD16(-) NK cells in the blood and, in CMV(+) individuals, induced an increased frequency of mature CD56(dim)NKG2A(+)CD57(+) NK cells in the blood that persisted into latency. These results provide further evidence that NKG2C(+) NK cells are CMV specific and suggest that EBV infection alters the repertoire of NK cells in the blood.
Cell division in Escherichia coli cultures monitored at single cell resolution
Roostalu, Johanna; Jõers, Arvi; Luidalepp, Hannes; Kaldalu, Niilo; Tenson, Tanel
2008-01-01
Background A fundamental characteristic of cells is the ability to divide. To date, most parameters of bacterial cultures, including cell division, have been measured as cell population averages, assuming that all bacteria divide at a uniform rate. Results We monitored the division of individual cells in Escherichia coli cultures during different growth phases. Our experiments are based on the dilution of green fluorescent protein (GFP) upon cell division, monitored by flow cytometry. The results show that the vast majority of E. coli cells in exponentially growing cultures divided uniformly. In cultures that had been in stationary phase up to four days, no cell division was observed. However, upon dilution of stationary phase culture into fresh medium, two subpopulations of cells emerged: one that started dividing and another that did not. These populations were detectable by GFP dilution and displayed different side scatter parameters in flow cytometry. Further analysis showed that bacteria in the non-growing subpopulation were not dead, neither was the difference in growth capacity reducible to differences in stationary phase-specific gene expression since we observed uniform expression of several stress-related promoters. The presence of non-growing persisters, temporarily dormant bacteria that are tolerant to antibiotics, has previously been described within growing bacterial populations. Using the GFP dilution method combined with cell sorting, we showed that ampicillin lyses growing bacteria while non-growing bacteria retain viability and that some of them restart growth after the ampicillin is removed. Thus, our method enables persisters to be monitored even in liquid cultures of wild type strains in which persister formation has low frequency. Conclusion In principle, the approaches developed here could be used to detect differences in cell division in response to different environmental conditions and in cultures of unicellular organisms other than E. coli. PMID:18430255
Cell Division Induces and Switches Coherent Angular Motion within Bounded Cellular Collectives.
Siedlik, Michael J; Manivannan, Sriram; Kevrekidis, Ioannis G; Nelson, Celeste M
2017-06-06
Collective cell migration underlies many biological processes, including embryonic development, wound healing, and cancer progression. In the embryo, cells have been observed to move collectively in vortices using a mode of collective migration known as coherent angular motion (CAM). To determine how CAM arises within a population and changes over time, here, we study the motion of mammary epithelial cells within engineered monolayers, in which the cells move collectively about a central axis in the tissue. Using quantitative image analysis, we find that CAM is significantly reduced when mitosis is suppressed. Particle-based simulations recreate the observed trends, suggesting that cell divisions drive the robust emergence of CAM and facilitate switches in the direction of collective rotation. Our simulations predict that the location of a dividing cell, rather than the orientation of the division axis, facilitates the onset of this motion. These predictions agree with experimental observations, thereby providing, to our knowledge, new insight into how cell divisions influence CAM within a tissue. Overall, these findings highlight the dynamic nature of CAM and suggest that regulating cell division is crucial for tuning emergent collective migratory behaviors, such as vortical motions observed in vivo. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Coman, Garrett; Zinsmeister, Chris; Norris, Patricia
2015-01-01
Workers are exposed to potential irritants and allergens with constant introduction of new industrial chemicals in the workplace. Characterize the final diagnoses, demographics, occupations, exposures, clinical presentations, patch test results, dermatologic histories, and risk factors of workers evaluated for suspected work-related allergic contact dermatitis (ACD). A retrospective chart review of 310 workers' compensation independent medical examinations evaluated for suspected work-related ACD was performed. Workers were seen in a community dermatology clinic in Portland, Oregon, from 2005 to 2014. Evaluation included history, physical examination, patch testing, and further diagnostic workup when indicated. Hand dermatitis was the most common presentation (n = 148, 47.7%). Prevalent occupations included health care workers (n = 51, 16.5%), custodial staff (n = 41, 13.2%), and machinists (n = 36, 11.6%). Allergic contact dermatitis (47.5%) was more common than irritant contact dermatitis (ICD) (38.9%) in those diagnosed as having occupational skin disease (n = 185). The highest-frequency work-related allergens were thiuram mix (21 of 88, 23.9%), carba mix (20 of 88, 22.7%), potassium dichromate (9 of 88, 10.2%), and epoxy resin (9 of 88, 10.2%). Allergic contact dermatitis and ICD are common occupational skin disorders. In this population of workers' compensation referrals, ACD was more common, with 73.3% of those cases work related, compared with 86.7% of ICD. Blue collar work and wet work were risk factors for the development of ACD and ICD.
Gatica-Ortega, Maria-Elena; Pastor-Nieto, Maria-Antonia; Mercader-García, Pedro; Silvestre-Salvador, Juan-Francisco
2017-12-01
Allergic contact dermatitis (ACD) caused by (meth)acrylates has been described both in occupational and in non-occupational settings. To evaluate the clinical patterns, the most frequent allergens and the prognosis in patients sensitized to (meth)acrylates in long-lasting nail polish. The files of patients with ACD caused by (meth)acrylates in long-lasting nail polish diagnosed between January 2013 and June 2016 in four dermatology departments in Spain were reviewed. Patients were followed up by telephone interview. Overall, 2353 patients were patch tested. Forty-three (1.82%) were diagnosed with ACD caused by (meth)acrylates in long-lasting nail polish during that period; all were female, and all had hand dermatitis. Patients were mostly less than 40 years old (72.1%), non-atopic (95.4%) and had an occupational cause of their dermatitis (93%), which developed ∼10.1 months after they had started to use this technique. The most frequent positive allergens were: 2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, and tetrahydrofurfuryl methacrylate. Eight of the 22 interviewed patients were able to improve their working technique and used 4H® protective material (fingerstalls/gloves). Long-lasting nail polishes have become widespread, and it is a matter of concern that we may be facing a new epidemic of ACD caused by these. Policies regulating their use are urgently needed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Barbosa, Rodrigo Labello; Pereira, Karen Signori; Dias, Viviane Liotti; Schmidt, Flávio Luis; Alves, Delma Pegolo; Guaraldo, Ana Maria Aparecida; Passos, Luiz Augusto Corrêa
2016-10-01
Outbreaks of acute Chagas disease (ACD) in northern Brazil can be caused by the ingestion of unprocessed açai pulp contaminated with Trypanosoma cruzi . The aim of this study was to determine the minimum thermal process required to inactivate T. cruzi in açai pulp. Trypomastigotes (100,000) of T. cruzi Y strain were added to 0.15 M NaCl or açai pulp and continuously mixed while being heat treated at 37 to 49°C for up to 1 h. When necessary, parasites were separated from açai pulp by forced sieving. Inocula were administrated intraperitoneally in inbred immunodeficient C.B-17-Prkdc scid /Pas Unib mice, and the recipients were monitored for parasitemia and mortality. Mice received prophylactic antibiotic therapy by using cephalexin to prevent bacterial infection from the açai pulp. T. cruzi retained its virulence in 0.15 M NaCl and açai pulp at 44 ± 0.1°C for 10 min and at 43 ± 0.1°C for 20 min, respectively, causing ACD and death in mice up to 24 days after infection. Incubation of açai pulp inoculum above 43°C for 20 min neutralized T. cruzi virulence, thereby preventing ACD and death in murine recipients. The heating of açai pulp above 43°C for 20 min is a practical and effective measure to prevent foodborne ACD caused by T. cruzi .
Higgins, Claire L; Palmer, Amanda M; Cahill, Jennifer L; Nixon, Rosemary L
2016-10-01
Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Lee, Chang Jae; Chung, Tae Nyoung; Bae, Jinkun; Kim, Eui Chung; Choi, Sung Wook; Kim, Ok Jun
2015-01-01
Objective Current guidelines for cardiopulmonary resuscitation recommend chest compressions (CC) during 50% of the duty cycle (DC) in part because of the ease with which individuals may learn to achieve it with practice. However, no consideration has been given to a possible interaction between DC and depth of CC, which has been the subject of recent study. Our aim was to determine if 50% DC is inappropriate to achieve sufficient chest compression depth for female and light rescuers. Methods Previously collected CC data, performed by senior medical students guided by metronome sounds with various down-stroke patterns and rates, were included in the analysis. Multiple linear regression analysis was performed to determine the association between average compression depth (ACD) with average compression rate (ACR), DC, and physical characteristics of the performers. Expected ACD was calculated for various settings. Results DC, ACR, body weight, male sex, and self-assessed physical strength were significantly associated with ACD in multivariate analysis. Based on our calculations, with 50% of DC, only men with ACR of 140/min or faster or body weight over 74 kg with ACR of 120/min can achieve sufficient ACD. Conclusion A shorter DC is independently correlated with deeper CC during simulated cardiopulmonary resuscitation. The optimal DC recommended in current guidelines may be inappropriate for achieving sufficient CD, especially for female or lighter-weight rescuers. PMID:27752567
Vilupuru, Abhiram S.; Glasser, Adrian
2010-01-01
Experiments were undertaken to understand the relationship between dynamic accommodative refractive and biometric (lens thickness (LT), anterior chamber depth (ACD) and anterior segment length (ASL=ACD+LT)) changes during Edinger–Westphal stimulated accommodation in rhesus monkeys. Experiments were conducted on three rhesus monkeys (aged 11·5, 4·75 and 4·75 years) which had undergone prior, bilateral, complete iridectomies and implantation of a stimulating electrode in the Edinger–Westphal (EW) nucleus. Accommodative refractive responses were first measured dynamically with video-based infrared photorefraction and then ocular biometric responses were measured dynamically with continuous ultrasound biometry (CUB) during EW stimulation. The same stimulus amplitudes were used for the refractive and biometric measurements to allow them to be compared. Main sequence relationships (ratio of peak velocity to amplitude) were calculated. Dynamic accommodative refractive changes are linearly correlated with the biometric changes and accommodative biometric changes in ACD, ASL and LT show systematic linear correlations with increasing accommodative amplitudes. The relationships are relatively similar for the eyes of the different monkeys. Dynamic analysis showed that main sequence relationships for both biometry and refraction are linear. Although accommodative refractive changes in the eye occur primarily due to changes in lens surface curvature, the refractive changes are well correlated with A-scan measured accommodative biometric changes. Accommodative changes in ACD, LT and ASL are all well correlated over the full extent of the accommodative response. PMID:15721617
Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy.
Mukherjee, Subhas; Brat, Daniel J
2017-01-01
Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.
Rodilla, V
1993-08-01
It has recently been described that cisplatin is an agent able to induce binucleated cells (BC) in cultured CHO cells. Both the origin and the significance of those cells within a population are unknown although several hypothesis have been suggested such as blocking of cytokinesis or cell fusion. Using interval photography we have found that at least two mechanisms are involved in the production of BC. These cells can arise in a culture as a result of an incomplete process of cell division, i.e. karyokinesis with incomplete cytokinesis or as a result of the mitotic division of a pre-existent BC. The mitotic division of a BC can give rise to different types of daughter cells. These BC sometimes enter mitosis but fail to divide and as a consequence they remain BC. When the process of division is successful (in the vast majority of cases), the results that have been found are either two mononucleated cells or one mononucleated and one binucleated cell. The possible implications and significance of BC and BC with micronuclei in a given population are discussed.
Dumollard, Rémi; Minc, Nicolas; Salez, Gregory; Aicha, Sameh Ben; Bekkouche, Faisal; Hebras, Céline; Besnardeau, Lydia; McDougall, Alex
2017-01-01
The ascidian embryo is an ideal system to investigate how cell position is determined during embryogenesis. Using 3D timelapse imaging and computational methods we analyzed the planar cell divisions in ascidian early embryos and found that spindles in every cell tend to align at metaphase in the long length of the apical surface except in cells undergoing unequal cleavage. Furthermore, the invariant and conserved cleavage pattern of ascidian embryos was found to consist in alternate planar cell divisions between ectoderm and endomesoderm. In order to test the importance of alternate cell divisions we manipulated zygotic transcription induced by β-catenin or downregulated wee1 activity, both of which abolish this cell cycle asynchrony. Crucially, abolishing cell cycle asynchrony consistently disrupted the spindle orienting mechanism underpinning the invariant cleavage pattern. Our results demonstrate how an evolutionary conserved cell cycle asynchrony maintains the invariant cleavage pattern driving morphogenesis of the ascidian blastula. DOI: http://dx.doi.org/10.7554/eLife.19290.001 PMID:28121291
1975-01-01
A wide variety of inhibitors (drugs, antibiotics, and antimetabolites) will block cell division within an ongoing cell cycle in autotrophic cultures of Chlamydomonas reinhardtii. To determine when during the cell cycle a given inhibitor is effective in preventing cell division, a technique is described which does not rely on the use of synchronous cultures. The technique permits the measurement of transition points, the cell cycle stage at which the subsequent cell division becomes insensitive to the effects of an inhibitor. A map of transition points in the cell cycle reveals that they are grouped into two broad periods, the second and fourth quarters. In general, inhibitors which block organellar DNA, RNA, and protein synthesis have second-quarter transition points, while those which inhibit nuclear cytoplasmic macromolecular synthesis have fourth-quarter transition points. The specific grouping of these transition points into two periods suggests that the synthesis of organellar components is completed midway through the cell cycle and that the synthesis of nonorganellar components required for cell division is not completed until late in the cell cycle. PMID:1176526
Logsdon, Michelle M; Aldridge, Bree B
2018-01-01
Model bacteria, such as E. coli and B. subtilis , tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.
Winquist, Raymond J; Hall, Amy B; Eustace, Brenda K; Furey, Brinley F
2014-09-15
Stem cells subserve repair functions for the lifetime of the organism but, as a consequence of this responsibility, are candidate cells for accumulating numerous genetic and/or epigenetic aberrations leading to malignant transformation. However, given the importance of this guardian role, stem cells likely harbor some process for maintaining their precious genetic code such as non-random segregation of chromatid strands as predicted by the Immortal Strand Hypothesis (ISH). Discerning such non-random chromosomal segregation and asymmetric cell division in normal or cancer stem cells has been complicated by methodological shortcomings but also by differing division kinetics amongst tissues and the likelihood that both asymmetric and symmetric cell divisions, dictated by local extrinsic factors, are operant in these cells. Recent data suggest that cancer stem cells demonstrate a higher incidence of symmetric versus asymmetric cell division with both daughter cells retaining self-renewal characteristics, a profile which may underlie poorly differentiated morphology and marked clonal diversity in tumors. Pathways and targets are beginning to emerge which may provide opportunities for preventing such a predilection in cancer stem cells and that will hopefully translate into new classes of chemotherapeutics in oncology. Thus, although the existence of the ISH remains controversial, the shift of cell division dynamics to symmetric random chromosome segregation/self-renewal, which would negate any likelihood of template strand retention, appears to be a surrogate marker for the presence of highly malignant tumorigenic cell populations. Copyright © 2014 Elsevier Inc. All rights reserved.
Kopecká, Marie
2014-01-01
Cryptococcus neoformans is one of the most important human fungal pathogens. Its cells contain rich microtubules required for nuclear division and rich F-actin cytoskeletons for cell division. Disruption of microtubules by a microtubule inhibitor should block nuclear division, and disruption of F-actin by an actin inhibitor should block cell division. We investigated the effects of microtubule and actin inhibitors to find out whether the cytoskeletons of C. neoformans can become a new anti-fungal target for the inhibition of cell division, when examined at the ultrastructural level. Cells treated with the microtubule inhibitors vincristine (VIN) and methyl benzimidazole-2-ylcarbamate (BCM) and the actin inhibitor latrunculin A (LA), in yeast extract peptone dextrose medium, were examined by scanning (SEM) and transmission electron microscopy (TEM), and the cell number was counted using a Bürker chamber. After 2 days of inhibition with VIN, BCM or LA, the cells did not divide, but later, resistant, proliferating cells appeared in all samples. With combined microtubule and actin inhibitors (VIN + LA or BCM + LA), cells did not divide during 6 or even 14 days, and no resistant cells originated. TEM showed that the inhibited cells were without cytoplasm and were dead; only empty cell walls persisted with reduced capsules, shown on SEM. Combined microtubule and actin inhibitors (VIN + LA or BCM + LA), have lethal effects on C. neoformans cells and no resistant cells originate. © 2015 S. Karger AG, Basel
Genome organization during the cell cycle: unity in division.
Golloshi, Rosela; Sanders, Jacob T; McCord, Rachel Patton
2017-09-01
During the cell cycle, the genome must undergo dramatic changes in structure, from a decondensed, yet highly organized interphase structure to a condensed, generic mitotic chromosome and then back again. For faithful cell division, the genome must be replicated and chromosomes and sister chromatids physically segregated from one another. Throughout these processes, there is feedback and tension between the information-storing role and the physical properties of chromosomes. With a combination of recent techniques in fluorescence microscopy, chromosome conformation capture (Hi-C), biophysical experiments, and computational modeling, we can now attribute mechanisms to many long-observed features of chromosome structure changes during cell division. Apparent conflicts that arise when integrating the concepts from these different proposed mechanisms emphasize that orchestrating chromosome organization during cell division requires a complex system of factors rather than a simple pathway. Cell division is both essential for and threatening to proper genome organization. As interphase three-dimensional (3D) genome structure is quite static at a global level, cell division provides an important window of opportunity to make substantial changes in 3D genome organization in daughter cells, allowing for proper differentiation and development. Mistakes in the process of chromosome condensation or rebuilding the structure after mitosis can lead to diseases such as cancer, premature aging, and neurodegeneration. WIREs Syst Biol Med 2017, 9:e1389. doi: 10.1002/wsbm.1389 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.
TfVPS32 Regulates Cell Division in the Parasite Tritrichomonas foetus.
Iriarte, Lucrecia S; Midlej, Victor; Frontera, Lorena S; Moros Duarte, Daniel; Barbeito, Claudio G; de Souza, Wanderley; Benchimol, Marlene; de Miguel, Natalia; Coceres, Veronica M
2018-01-01
The flagellated protist Tritrichomonas foetus is a parasite that causes bovine trichomonosis, a major sexually transmitted disease in cattle. Cell division has been described as a key player in controlling cell survival in other cells, including parasites but there is no information on the regulation of this process in T. foetus. The regulation of cytokinetic abscission, the final stage of cell division, is mediated by members of the ESCRT (endosomal sorting complex required for transport) machinery. VPS32 is a subunit within the ESCRTIII complex and here, we report that TfVPS32 is localized on cytoplasmic vesicles and a redistribution of the protein to the midbody is observed during the cellular division. In concordance with its localization, deletion of TfVPS32 C-terminal alpha helices (α5 helix and/or α4-5 helix) leads to abnormal T. foetus growth, an increase in the percentage of multinucleated parasites and cell cycle arrest at G2/M phase. Together, these results indicate a role of this protein in controlling normal cell division. © 2017 The Author(s) Journal of Eukaryotic Microbiology © 2017 International Society of Protistologists.
Todd, C G; Leslie, K E; Millman, S T; Bielmann, V; Anderson, N G; Sargeant, J M; DeVries, T J
2017-01-01
The objectives of this study were to evaluate the effects of free-access acidified milk replacer feeding on the pre- and postweaning health of dairy and veal calves. Individually housed calves were systematically assigned at birth to 1 of 2 feeding programs: free-access feeding (ad libitum) of acidified milk replacer (ACD, n=249) or traditional restricted feeding (3L fed twice daily) of milk replacer (RES, n=249). Calves were fed milk replacer containing 24% crude protein and 18% fat. Acidified milk replacer was prepared to a target pH between 4.0 and 4.5 using formic acid. Calves were weaned off milk replacer at approximately 6wk of age. Weaning occurred over 5d, and during this weaning period, ACD calves had access to milk replacer for 12h/d and RES calves were offered only one feeding of milk replacer (3 L) daily. Calves were monitored daily for signs of disease. Fecal consistency scores were assigned each week from birth until weaning. A subset of calves was systematically selected for fecal sampling at 3 time points between 7 and 27d of age. Fecal samples were analyzed for enterotoxigenic Escherichia coli F5, Cryptosporidium parvum, rotavirus, and coronavirus. Hip width, hip height, body length, heart girth, and body weight were measured at birth and weaning. Postweaning body weight measurements were collected from the heifers at approximately 8mo of age. Postweaning body weight and carcass grading information was collected from the veal calves at slaughter once a live weight between 300 and 350kg had been achieved. The odds of ACD calves being treated for a preweaning disease event tended to be lower than that of the RES calves (1.2 vs. 5.2%, respectively). Preweaning mortality, postweaning disease treatment, and postweaning mortality did not differ between feeding treatments. The ACD feeding treatment supported greater preweaning average daily gain (0.59 vs. 0.43kg/d) and structural growth than RES feeding. Postweaning average daily gain and carcass characteristics were similar for ACD and RES calves. These results indicate that free-access acidified milk replacer feeding tended to support improved health, and greater body weight gain and structural growth during the preweaning period; these effects did not persist in the postweaning period. The growth advantage observed before weaning in the ACD calves likely disappeared due to the weaning methods used. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Z ring as executor of bacterial cell division.
Dajkovic, Alex; Lutkenhaus, Joe
2006-01-01
It has become apparent that bacteria possess ancestors of the major eukaryotic cytoskeletal proteins. FtsZ, the ancestral homologue of tubulin, assembles into a cytoskeletal structure associated with cell division, designated the Z ring. Formation of the Z ring represents a major point of both spatial and temporal regulation of cell division. Here we discuss findings concerning the structure and the formation of the ring as well as its spatial and temporal regulation.
Zupan, John R.; Cameron, Todd A.; Anderson-Furgeson, James; Zambryski, Patricia C.
2013-01-01
Growth and cell division in rod-shaped bacteria have been primarily studied in species that grow predominantly by peptidoglycan (PG) synthesis along the length of the cell. Rhizobiales species, however, predominantly grow by PG synthesis at a single pole. Here we characterize the dynamic localization of several Agrobacterium tumefaciens components during the cell cycle. First, the lipophilic dye FM 4-64 predominantly stains the outer membranes of old poles versus growing poles. In cells about to divide, however, both poles are equally labeled with FM 4-64, but the constriction site is not. Second, the cell-division protein FtsA alternates from unipolar foci in the shortest cells to unipolar and midcell localization in cells of intermediate length, to strictly midcell localization in the longest cells undergoing septation. Third, the cell division protein FtsZ localizes in a cell-cycle pattern similar to, but more complex than, FtsA. Finally, because PG synthesis is spatially and temporally regulated during the cell cycle, we treated cells with sublethal concentrations of carbenicillin (Cb) to assess the role of penicillin-binding proteins in growth and cell division. Cb-treated cells formed midcell circumferential bulges, suggesting that interrupted PG synthesis destabilizes the septum. Midcell bulges contained bands or foci of FtsA-GFP and FtsZ-GFP and no FM 4-64 label, as in untreated cells. There were no abnormal morphologies at the growth poles in Cb-treated cells, suggesting unipolar growth uses Cb-insensitive PG synthesis enzymes. PMID:23674672
NASA Astrophysics Data System (ADS)
Kemper, Björn; Bauwens, Andreas; Vollmer, Angelika; Ketelhut, Steffi; Langehanenberg, Patrik; Müthing, Johannes; Karch, Helge; von Bally, Gert
2010-05-01
Digital holographic microscopy (DHM) enables quantitative multifocus phase contrast imaging for nondestructive technical inspection and live cell analysis. Time-lapse investigations on human brain microvascular endothelial cells demonstrate the use of DHM for label-free dynamic quantitative monitoring of cell division of mother cells into daughter cells. Cytokinetic DHM analysis provides future applications in toxicology and cancer research.
The price of independence: cell separation in fission yeast.
Martín-García, Rebeca; Santos, Beatriz
2016-04-01
The ultimate goal of cell division is to give rise to two viable independent daughter cells. A tight spatial and temporal regulation between chromosome segregation and cytokinesis ensures the viability of the daughter cells. Schizosaccharomyces pombe, commonly known as fission yeast, has become a leading model organism for studying essential and conserved mechanisms of the eukaryotic cell division process. Like many other eukaryotic cells it divides by binary fission and the cleavage furrow undergoes ingression due to the contraction of an actomyosin ring. In contrast to mammalian cells, yeasts as cell-walled organisms, also need to form a division septum made of cell wall material to complete the process of cytokinesis. The division septum is deposited behind the constricting ring and it will constitute the new ends of the daughter cells. Cell separation also involves cell wall degradation and this process should be precisely regulated to avoid cell lysis. In this review, we will give a brief overview of the whole cytokinesis process in fission yeast, from the positioning and assembly of the contractile ring to the final step of cell separation, and the problems generated when these processes are not precise.
GEMINI-TITAN (GT)-3 - WEIGHTLESSNESS EXPERIMENT - AMES RESEARCH CENTER (ARC), CA
1965-03-01
S65-18762 (March 1965) --- Effects of the weightless environment on cell division, the basic growth process for living tissue, will be studied during the Gemini-Titan 3 flight scheduled for March 23, 1965. A spiny black sea urchin (upper left) is stimulated by mild electric shock or potassium chloride. As a result it sheds many thousands of eggs. When fertilized, these eggs become actively dividing cells very similar in basic processes to cells of other animals, including humans. These pictures show stages of cell division. At upper right is a single cell; at lower right cell divisions have produced many cells. Cell photos are magnified about 700 times, and all cells shown are too small to be seen by the naked eye. (Photos at upper right and lower left are of sea urchin eggs. Group of cells at lower right are from a sand dollar, which like the sea urchin, is an Echinoderm. Its eggs are virtually identical and are used interchangeably with those of the sea urchin in NASA Ames Center weightlessness experiments.) The Gemini experiment will involve cell division like that shown here. This will take place during several hours of weightlessness aboard the Gemini spacecraft. The experiment will be flown back to laboratories at Cape Kennedy after spacecraft recovery. It has been designed so that any abnormal cell division found by postflight analysis should suggest that the weightless environment has effects on individual cells. This might mean hazards for prolonged periods of manned spaceflight.
Etchells, J Peter; Provost, Claire M; Mishra, Laxmi; Turner, Simon R
2013-05-01
In plants, the cambium and procambium are meristems from which vascular tissue is derived. In contrast to most plant cells, stem cells within these tissues are thin and extremely long. They are particularly unusual as they divide down their long axis in a highly ordered manner, parallel to the tangential axis of the stem. CLAVATA3-LIKE/ESR-RELATED 41 (CLE41) and PHLOEM INTERCALATED WITH XYLEM (PXY) are a multifunctional ligand-receptor pair that regulate vascular cell division, vascular organisation and xylem differentiation in vascular tissue. A transcription factor gene, WUSCHEL HOMEOBOX RELATED 4 (WOX4) has been shown to act downstream of PXY. Here we show that WOX4 acts redundantly with WOX14 in the regulation of vascular cell division, but that these genes have no function in regulating vascular organisation. Furthermore, we identify an interaction between PXY and the receptor kinase ERECTA (ER) that affects the organisation of the vascular tissue but not the rate of cell division, suggesting that cell division and vascular organisation are genetically separable. Our observations also support a model whereby tissue organisation and cell division are integrated via PXY and ER signalling, which together coordinate development of different cell types that are essential for normal stem formation.
Dorca-Fornell, Carmen; Pajor, Radoslaw; Lehmeier, Christoph; Pérez-Bueno, Marísa; Bauch, Marion; Sloan, Jen; Osborne, Colin; Rolfe, Stephen; Sturrock, Craig; Mooney, Sacha; Fleming, Andrew
2013-01-01
The causal relationship between cell division and growth in plants is complex. Although altered expression of cell-cycle genes frequently leads to altered organ growth, there are many examples where manipulation of the division machinery leads to a limited outcome at the level of organ form, despite changes in constituent cell size. One possibility, which has been under-explored, is that altered division patterns resulting from manipulation of cell-cycle gene expression alter the physiology of the organ, and that this has an effect on growth. We performed a series of experiments on retinoblastoma-related protein (RBR), a well characterized regulator of the cell cycle, to investigate the outcome of altered cell division on leaf physiology. Our approach involved combination of high-resolution microCT imaging and physiological analysis with a transient gene induction system, providing a powerful approach for the study of developmental physiology. Our investigation identifies a new role for RBR in mesophyll differentiation that affects tissue porosity and the distribution of air space within the leaf. The data demonstrate the importance of RBR in early leaf development and the extent to which physiology adapts to modified cellular architecture resulting from altered cell-cycle gene expression. PMID:24118480
NASA Technical Reports Server (NTRS)
Cai, Li; Hayes, Nancy L.; Takahashi, Takao; Caviness, Verne S Jr; Nowakowski, Richard S.
2002-01-01
Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neurogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types. Copyright 2002 Wiley-Liss, Inc.
Ianzini, Fiorenza; Kosmacek, Elizabeth A.; Nelson, Elke S.; Napoli, Eleonora; Erenpreisa, Jekaterina; Kalejs, Martins; Mackey, Michael A.
2009-01-01
Cancer is frequently characterized histologically by the appearance of large cells that are either aneuploid or polyploid. Aneuploidy and polyploidy are hallmarks of radiation-induced mitotic catastrophe (MC), a common phenomenon occurring in tumor cells with impaired p53 function exposed to various cytotoxic and genotoxic agents. MC is characterized by altered expression of mitotic regulators, untimely and abnormal cell division, delayed DNA damage, and changes in morphology. We report here that cells undergoing radiation-induced MC are more plastic with regards to ploidy and that this plasticity allows them to reorganize their genetic material through reduction divisions to produce smaller cells morphologically indistinguishable from control cells. Experiments conducted with the Large Scale Digital Cell Analysis System (LSDCAS) are discussed that show that a small fraction of polyploid cancer cells formed via radiation-induced MC can survive and start a process of depolyploidization that yields various outcomes. While most multipolar divisions failed and cell fusion occurred; some of these divisions were successful and originated a variety of cell progeny characterized by different ploidy. Among these ploidy phenotypes, a progeny of small mononucleated cells, indistinguishable from the untreated control cells, is often seen. We report here evidence that meiosis-specific genes are expressed in the polyploid cells during depolyploidization. Tumor cells might take advantage of the temporary change from a pro-mitotic to a pro-meiotic division regimen to facilitate depolyploidization and restore the proliferative state of the tumor cell population. These events might be mechanisms by which tumor progression and resistance to treatment occur in vivo. PMID:19258501
Cell cycles and cell division in the archaea.
Samson, Rachel Y; Bell, Stephen D
2011-06-01
Until recently little was known about the cell cycle parameters and division mechanisms of archaeal organisms. Although this is still the case for the majority of archaea, significant advances have been made in some model species. The information that has been gleaned thus far points to a remarkable degree of diversity within the archaeal domain of life. More specifically, members of distinct phyla have very different chromosome copy numbers, replication control systems and even employ distinct machineries for cell division. Copyright © 2011 Elsevier Ltd. All rights reserved.
Studying cytokinesis in Drosophila epithelial tissues.
Pinheiro, D; Bellaïche, Y
2017-01-01
Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.
2007-07-20
Haughton-Mars Project: - Photo credit to Matt Deans (NASA) K-10 Rover 'Red' base camp at Haughton Creater Devon Island, Nunavut, in the Canadian high arctic. Which lies in the 'frost rubble zone' of the Earth, i.e., in a polar desert environment and is the only crater known to lie in such an environment. Beginning in 1997, the crater and its surroundings are studied as a promising Mars analog by the NASA-led Haughton-Mars Project. (photo reference K10-R-haughton.jpg - crop of ACD07-0170-4 MCD_0859.JPG)
Study of the mechanism of diatom cell division by means of 29Si isotope tracing
NASA Astrophysics Data System (ADS)
Audinot, J.-N.; Guignard, C.; Migeon, H.-N.; Hoffmann, L.
2006-07-01
Diatoms are delicate unicellular organisms enclosed in a silica frustule, that is made up of two valves. Multiplication of the diatoms occurs by ordinary mitotic cell division. During cell division each cell produces two daughter cells, each of them keeping one of the two valves of the mother cell and producing a new valve by absorbing the silicon present in the environment. The NanoSIMS 50 allows ion imaging to be performed on diatoms in order to determine the site of fixation of silicon. The aim of this study was to observe and compare the mechanism of the construction of the new valve after cell division. To this end, different types of diatoms have been transferred in a culture medium enriched with 29Si and after several days, the distribution of the different isotopes of silicon has been determined by NanoSIMS50 imaging. The construction of new valves has been observed and the isotopic ratio has been determined.
FORMATION OF INTRACYTOPLASMIC MEMBRANE SYSTEM OF MYCOBACTERIA RELATED TO CELL DIVISION
Imaeda, Tamotsu; Ogura, Mituo
1963-01-01
Imaeda, Tamotsu (Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela) and Mitua Ogura. Formation of intracytoplasmic membrane system of mycobacteria related to cell division. J. Bacteriol. 85:150–163. 1963.—Mycobacterium leprae, M. lepraemurium, and a Mycobacterium sp. were observed with an electron microscope. In these bacilli, the three-dimensional structure of the intracytoplasmic membrane system consists of tubular infoldings of the invaginated plasma membrane. The moderately dense substance, presumably representing the cell-wall precursor, is found in the membranous system, especially in the rapid growth phase of mycobacteria. This system always shows an intimate relationship with cell division. A low-density zone, probably corresponding to the low-density substance which coats the cell wall, appears in the connecting regions of the system and in the longitudinal portion of the cell wall. These zones extend centripetally, and the separation of the cell wall occurs after the two zones meet. Based on these results, we hypothesize that the intracytoplasmic membrane system may produce cell-wall material during cell division of mycobacteria. Images PMID:13956365
Nijhout, H Frederik; Cinderella, Margaret; Grunert, Laura W
2014-03-01
The wings of butterflies and moths develop from imaginal disks whose structure is always congruent with the final adult wing. It is therefore possible to map every point on the imaginal disk to a location on the adult wing throughout ontogeny. We studied the growth patterns of the wings of two distantly related species with very different adult wing shapes, Junonia coenia and Manduca sexta. The shape of the wing disks change throughout their growth phase in a species-specific pattern. We measured mitotic densities and mitotic orientation in successive stages of wing development approximately one cell division apart. Cell proliferation was spatially patterned, and the density of mitoses was highly correlated with local growth. Unlike other systems in which the direction of mitoses has been viewed as the primary determinant of directional growth, we found that in these two species the direction of growth was only weakly correlated with the orientation of mitoses. Directional growth appears to be imposed by a constantly changing spatial pattern of cell division coupled with a weak bias in the orientation of cell division. Because growth and cell division in imaginal disk require ecdysone and insulin signaling, the changing spatial pattern of cell division may due to a changing pattern of expression of receptors or downstream elements in the signaling pathways for one or both of these hormones. Evolution of wing shape comes about by changes in the progression of spatial patterns of cell division. © 2014 Wiley Periodicals, Inc.
Stoynova-Bakalova, E; Petrov, P; Gigova, L; Ivanova, N
2011-01-01
The effect of endogenous cytokinins on the pattern of palisade cell division post-germination does not depend on the conditions of cotyledon development -in planta (attached to seedlings) or in vitro (isolated from dry zucchini seeds and cultured on water). In cotyledons originating from 4-day-old seedlings (experimental system 1), exogenous cytokinin temporarily (in the first 2 day of cultivation) enhanced post-mitotic cell enlargement of palisade cells, mainly due to enhanced water uptake and use of cell storage compounds, all of which lead to cotyledon senescence. Cytokinin is not able to resume the completed palisade cell division on day 5. As a result, the number of cells and the final areas of treated and control cotyledons are quite similar. By contrast, the effects of cytokinin on cotyledons isolated from dry seeds (experimental system 2) are better expressed, promoting an increase in number of palisade cells accompanied by additional cotyledon area enlargement. However, the prolonged post-mitotic cell expansion in control cotyledons compensates for the reduced speed of cell growth and division activity and decreases differences in final cotyledon area between treatments. The results define cell division as the primary target of cytokinin stimulation in cotyledon tissues competent for division, and determine the temporal patterns of palisade cell cycling related to cotyledon age. This knowledge permits a better choice of experimental system to study effects on cell proliferation and cell growth, as well as cell enlargement and senescence-related events using physiologically homogeneous material. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.
Flagellation of Pseudomonas aeruginosa in newly divided cells
NASA Astrophysics Data System (ADS)
Zhao, Kun; Lee, Calvin; Anda, Jaime; Wong, Gerard
2015-03-01
For monotrichous bacteria, Pseudomonas aeruginosa, after cell division, one daughter cell inherits the old flagellum from its mother cell, and the other grows a new flagellum during or after cell division. It had been shown that the new flagellum grows at the distal pole of the dividing cell when the two daughter cells haven't completely separated. However, for those daughter cells who grow new flagella after division, it still remains unknown at which pole the new flagellum will grow. Here, by combining our newly developed bacteria family tree tracking techniques with genetic manipulation method, we showed that for the daughter cell who did not inherit the old flagellum, a new flagellum has about 90% chances to grow at the newly formed pole. We proposed a model for flagellation of P. aeruginosa.
Regulation of Asymmetric Division and CD8+ T Lymphocyte Fate Specification by PKCζ and PKCλ/ι
Metz, Patrick J.; Arsenio, Janilyn; Kakaradov, Boyko; Kim, Stephanie H.; Remedios, Kelly A.; Oakley, Katherine; Akimoto, Kazunori; Ohno, Shigeo; Yeo, Gene W.; Chang, John T.
2015-01-01
During an immune response against a microbial pathogen, activated naïve T lymphocytes give rise to effector cells that provide acute host defense and memory cells that provide long-lived immunity. It has been shown that T lymphocytes can undergo asymmetric division, enabling the daughter cells to inherit unequal amounts of fate-determining proteins and thereby acquire distinct fates from their inception. Here, we show that the absence of the atypical protein kinase C (aPKC) isoforms, PKCζ and PKCλ/ι, disrupts asymmetric CD8+ T lymphocyte division. These alterations were associated with aberrant acquisition of a ‘pre-effector’ transcriptional program, detected by single-cell gene expression analyses, in lymphocytes that had undergone their first division in vivo and enhanced differentiation toward effector fates at the expense of memory fates. Together, these results demonstrate a role for aPKC in regulating asymmetric division and the specification of divergent CD8+ T lymphocyte fates early during an immune response. PMID:25617472
Cell-Division Behavior in a Heterogeneous Swarm Environment.
Erskine, Adam; Herrmann, J Michael
2015-01-01
We present a system of virtual particles that interact using simple kinetic rules. It is known that heterogeneous mixtures of particles can produce particularly interesting behaviors. Here we present a two-species three-dimensional swarm in which a behavior emerges that resembles cell division. We show that the dividing behavior exists across a narrow but finite band of parameters and for a wide range of population sizes. When executed in a two-dimensional environment the swarm's characteristics and dynamism manifest differently. In further experiments we show that repeated divisions can occur if the system is extended by a biased equilibrium process to control the split of populations. We propose that this repeated division behavior provides a simple model for cell-division mechanisms and is of interest for the formation of morphological structure and to swarm robotics.
Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells.
Wang, Jianyu; Sun, Zhiwei; Liu, Yongli; Kong, Liangsheng; Zhou, Shixia; Tang, Junlin; Xing, Hongmei Rosie
2017-11-14
Characterization of the stem-like properties of cancer stem cells (CSCs) remain indirect and qualitative, especially the ability of CSCs to undergo asymmetric cell division for self renewal and differentiation, a unique property of cells of stem origin. It is partly due to the lack of stable cellular models of CSCs. In this study, we developed a new approach for CSC isolation and purification to derive a CSC-enriched cell line (LLC-SE). By conducting five consecutive rounds of single cell cloning using the LLC-SE cell line, we obtained two distinct sub-population of cells within the Lewis lung cancer CSCs that employed largely symmetric division for self-renewal (LLC-SD) or underwent asymmetric division for differentiation (LLC-ASD). LLC-SD and LLC-ASD cell lines could be stably passaged in culture and be distinguished by cell morphology, stem cell marker, spheroid formation and subcutaneous tumor initiation efficiency, as well as orthotopic lung tumor growth, progression and survival. The ability LLC-ASD cells to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division. The more stem-like LLC-SD cells exhibited higher capacity for tumorigenesis and progression and shorter survival. As few as 10 LLC-SD could initiate subcutaneous tumor growth when transplanted to the athymic mice. Collectively, these observations suggest that the SD-type of cells appear to be on the top of the hierarchical order of the CSCs. Furthermore, they have lead to generated cellular models of CSC self-renewal for future mechanistic investigations.
Cyclin D regulation of a sexually dimorphic asymmetric cell division
Tilmann, Christopher; Kimble, Judith
2006-01-01
SUMMARY The C. elegans somatic gonadal precursor cell (SGP) divides asymmetrically to establish gonad-specific coordinates in both sexes. In addition, the SGP division is sexually dimorphic and initiates sex-specific programs of gonadogenesis. Wnt/MAPK signaling determines the gonadal axes, and the FKH-6 transcription factor specifies the male mode of SGP division. In this paper, we demonstrate that C. elegans cyclin D controls POP-1/TCF asymmetry in the SGP daughters as well as fkh-6 and rnr expression in the SGPs. Although cyclin D mutants have delayed SGP divisions, the cyclin D defects are not mimicked by other methods of retarding the SGP division. We find that EFL-1/E2F has an antagonistic effect on fkh-6 expression and gonadogenesis, which is relieved by cyclin D activity. We propose that cyclin D and other canonical regulators of the G1/S transition coordinate key regulators of axis formation and sex determination with cell cycle progression to achieve the sexually dimorphic SGP asymmetric division. PMID:16198291
CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions.
Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro
2016-01-01
Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine.
CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions
Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro
2016-01-01
ABSTRACT Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine. PMID:27104746
Problems and potentialities of cultured plant cells in retrospect and prospect
NASA Technical Reports Server (NTRS)
Steward, F. C.; Krikorian, A. D.
1979-01-01
The past, present and expected future accomplishments and limitations of plant cell and tissue culture are reviewed. Consideration is given to the pioneering insights of Haberlandt in 1902, the development of culture techniques, and past work on cell division, cell and tissue growth and development, somatic embryogenesis, and metabolism and respiration. Current activity in culture media and technique development for plant regions, organs, tissues, cells, protoplasts, organelles and embryos, totipotency, somatic embryogenesis and clonal propagation under normal and space conditions, biochemical potentialities, and genetic engineering is surveyed. Prospects for the investigation of the induced control of somatic cell division, the division of isolated protoplasts, the improvement of haploid cell cultures, liquid cultures for somatic embryogenesis, and the genetic control of development are outlined.
Dysphagia, short-term outcomes, and cost of care after anterior cervical disc surgery.
Starmer, Heather M; Riley, Lee H; Hillel, Alexander T; Akst, Lee M; Best, Simon R A; Gourin, Christine G
2014-02-01
Dysphonia and dysphagia are common complications of anterior cervical discectomy (ACD). We sought to determine the relationship between dysphagia and in-hospital mortality, complications, speech therapy/dysphagia training, length of hospitalization, and costs associated with ACD. Discharge data from the Nationwide Inpatient Sample for 1,649,871 patients who underwent ACD of fewer than four vertebrae for benign acquired disease between 2001 and 2010 were analyzed using cross-tabulations and multivariate regression modeling. Dysphagia was reported in 32,922 cases (2.0 %). Speech therapy/dysphagia training was reported in less than 0.1 % of all cases and in only 0.2 % of patients with dysphagia. Dysphagia was significantly associated with age ≥65 years (OR = 1.5 [95 % CI 1.4-1.7], P < 0.001), advanced comorbidity (OR = 2.3 [2.0-2.6], P < 0.001), revision surgery (OR = 2.7 [2.3-3.1], P < 0.001), disc prosthesis placement (OR = 1.5 [1.0-2.0], P = 0.029), and vocal cord paralysis (OR = 11.6 [8.3-16.1], P < 0.001). Dysphagia was a significant predictor of aspiration pneumonia (OR = 8.6 [6.7-10.9], P < 0.001), tracheostomy (OR = 2.3 [1.6-3.3], P < 0.001), gastrostomy (OR = 30.9 [25.3-37.8], P < 0.001), and speech therapy/dysphagia training (OR = 32.0 [15.4-66.4], P < 0.001). Aspiration pneumonia was significantly associated with in-hospital mortality (OR = 15.9 [11.0-23.1], P < 0.001). Dysphagia, vocal cord paralysis, and aspiration pneumonia were significant predictors of increased length of hospitalization and hospital-related costs, with aspiration pneumonia having the single largest impact on length of hospitalization and costs. Dysphagia is significantly associated with increased morbidity, length of hospitalization, and hospital-related costs in ACD patients. Despite the known risk of dysphagia in ACD patients and an established role for the speech-language pathologist in dysphagia management, speech-language pathology intervention appears underutilized in this population.
A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lye, Jessica; Dunn, Leon, E-mail: leon.dunn@arpansa.gov.au; Alves, Andrew
Purpose: The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. Methods: The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantomsmore » are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. Results: At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%–8%. Conclusions: The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.« less
Kessler, Ronald C.; Green, Jennifer Greif; Adler, Lenard A.; Barkley, Russell A.; Chatterji, Somnath; Faraone, Stephen V.; Finkelman, Matthew; Greenhill, Laurence L.; Gruber, Michael J.; Jewell, Mark; Russo, Leo J.; Sampson, Nancy A.; Van Brunt, David L.
2011-01-01
CONTEXT Controversy exists about the appropriate criteria for a diagnosis of adult attention-deficit/hyperactivity disorder (ADHD) OBJECTIVES To examine the structure and symptoms most predictive of DSM-IV adult ADHD. DESIGN Data come from clinical interviews in enriched sub-samples of the National Comorbidity Survey Replication (NCS-R) (n = 131) and a survey of a large managed healthcare plan (n = 214). The clinician-administered Adult ADHD Clinical Diagnostic Scale (ACDS) was used to assess childhood ADHD and expanded symptoms of current adult ADHD. Analyses examined stability of symptoms from childhood to adulthood, the structure of adult ADHD, and the adult symptoms most predictive of current clinical diagnoses. SETTING The ACDS was administered telephonically by clinical research interviewers with extensive experience in diagnosis and treatment of adult ADHD. PARTICIPANTS An enriched sample of community respondents MAIN OUTCOME MEASURES DSM-IV/ACDS diagnoses of adult ADHD RESULTS Almost half (45.7%) of respondents who had childhood ADHD continued to meet full DSM-IV criteria for current adult ADHD, with 94.9% of these cases having current attention-deficit disorder and 34.6% current hyperactivity disorder. Adult persistence was much greater for inattention than hyperactivity-impulsivity. Additional respondents met full criteria for current adult ADHD despite not having met full childhood criteria. A three-factor structure of adult symptoms included executive functioning, inattention-hyperactivity, and impulsivity. Stepwise logistic regression found executive functioning problems to be the most consistent and discriminating predictors of adult DSM-IV/ACDS ADHD. CONCLUSIONS These findings document the greater persistence of inattentive than hyperactive/impulsive childhood symptoms of ADHD in adulthood, but also show that inattention in not specific to ADHD, as it is strongly associated with other adult mental disorders. Executive functioning problems, in comparison, are more specific and consistently important predictors of DSM-IV adult ADHD despite not being in DSM-IV, suggesting that the number of executive functioning symptoms should be increased in DSM-V/ICD-11. PMID:21041618
Du, Chixin; Shen, Meixiao; Li, Ming; Zhu, Dexi; Wang, Michael R.; Wang, Jianhua
2012-01-01
Purpose To measure by ultra-long scan depth optical coherence tomography (UL-OCT) dimensional changes in the anterior segment of human eyes during accommodation. Design Evaluation of diagnostic test or technology. Participants Forty-one right eyes of healthy subjects with a mean age of 34 years (range, 22–41 years) and a mean refraction of −2.5±2.6 diopters (D) were imaged in two repeated measurements at minimal and maximal accommodation. Methods A specially adapted designed UL-OCT instrument was used to image from the front surface of the cornea to the back surface of the crystalline lens. Custom software corrected the optical distortion of the images and yielded the biometric measurements. The coefficient of repeatability (COR) and the intraclass correlation coefficient (ICC) were calculated to evaluate the repeatability and reliability. Main Outcome Measures Anterior segment parameters and associated repeatability and reliability upon accommodation. The dimensional results included central corneal thickness (CCT), anterior chamber depth and width (ACD, ACW), pupil diameter (PD), lens thickness (LT), anterior segment length (ASL=ACD+LT), lens central position (LCP=ACD+1/2LT) and horizontal radii of the lens anterior and posterior surface curvatures (LAC, LPC). Results Repeated measurements of each variable within each accommodative state did not differ significantly (P>0.05). The CORs and ICCs for CCT, ACW, ACD, LT, LCP, and ASL were excellent (1.2% to 3.59% and 0.998 to 0.877, respectively). They were higher for PD (18.90% to 21.63% and 0.880 to 0.874, respectively), and moderate for LAC and LPC (34.86% to 42.72% and 0.669 to 0.251, respectively) in the two accommodative states. Compared to minimal accommodation, PD, ACD, LAC, LPC, and LCP decreased and LT and ASL increased significantly at maximal accommodation (P<0.05), while CCT and ACW did not change (P>0.05). Conclusions UL-OCT measured changes in anterior segment dimensions during accommodation with good repeatability and reliability. During accommodation, the back surface of the lens became steeper as the lens moved forward. PMID:22902211
Jiang, Dan; Fang, Jingjing; Lou, Lamei; Zhao, Jinfeng; Yuan, Shoujiang; Yin, Liang; Sun, Wei; Peng, Lixiang; Guo, Baotai; Li, Xueyong
2015-01-01
Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1) show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1), nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogenous expression of NAL1 in fission yeast (Schizosaccharomyces pombe) further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division. PMID:25658704
Pluskal, Tomáš; Hayashi, Takeshi; Saitoh, Shigeaki; Fujisawa, Asuka; Yanagida, Mitsuhiro
2011-01-01
Glucose as a source of energy is centrally important to our understanding of life. We investigated the cell division–quiescence behavior of the fission yeast Schizosaccharomyces pombe under a wide range of glucose concentrations (0–111 mm). The mode of S. pombe cell division under a microfluidic perfusion system was surprisingly normal under highly diluted glucose concentrations (5.6 mm, 1/20 of the standard medium, within human blood sugar levels). Division became stochastic, accompanied by a curious division-timing inheritance, in 2.2–4.4 mm glucose. A critical transition from division to quiescence occurred within a narrow range of concentrations (2.2–1.7 mm). Under starvation (1.1 mm) conditions, cells were mostly quiescent and only a small population of cells divided. Under fasting (0 mm) conditions, division was immediately arrested with a short chronological lifespan (16 h). When cells were first glucose starved prior to fasting, they possessed a substantially extended lifespan (∼14 days). We employed a quantitative metabolomic approach for S. pombe cell extracts, and identified specific metabolites (e.g. biotin, trehalose, ergothioneine, S-adenosyl methionine and CDP-choline), which increased or decreased at different glucose concentrations, whereas nucleotide triphosphates, such as ATP, maintained high concentrations even under starvation. Under starvation, the level of S-adenosyl methionine increased sharply, accompanied by an increase in methylated amino acids and nucleotides. Under fasting, cells rapidly lost antioxidant and energy compounds, such as glutathione and ATP, but, in fasting cells after starvation, these and other metabolites ensuring longevity remained abundant. Glucose-starved cells became resistant to 40 mm H2O2 as a result of the accumulation of antioxidant compounds. PMID:21306563
Penagos, Homero; Ruepert, Clemens; Partanen, Timo; Wesseling, Catharina
2004-09-01
Irritant contact dermatitis and allergic contact dermatitis (ACD) are frequent among agricultural workers and require targeted interventions. Patch testing is necessary for differential diagnosis, but patch testing with pesticides is uncommon. This study explores the frequency of ACD and sensitization to pesticides among highly exposed banana plantation workers. Frequently and recently used pesticides on banana plantations in Divala, Panama, were documented. A pesticide patch test tray specific for this population was prepared. A structured interview was administered to 366 participants, followed by a complete skin examination. The pesticide patch test series, as well as a standard patch test series, was applied to 37 workers with dermatoses likely to be pesticide related and to 23 control workers without dermatoses. The pesticide patch tests identified 15 cases (41%) of ACD (20 positive reactions) among the 37 workers diagnosed with pesticide dermatosis. Three controls had allergic reactions to pesticides (4 positive reactions). The pesticides were carbaryl (5 cases), benomyl (4 cases), ethoprophos (3), chlorothalonil (2), imazalil (2), glyphosate (2), thiabendazole (2), chlorpyrifos (1), oxyfluorfen (1), propiconazole (1), and tridemorph (1). Ethoprophos and tridemorph had not been previously identified as sensitizers. Thus, the prevalence of ACD was 0.03 (15 of 366). On the basis of observed prevalences of positive patch-test reactions among the subgroups with and without dermatoses, we estimated that > or = 16% of the entire population may be sensitized to pesticides. Sensitization to pesticides among banana plantation workers is a frequent occupational health problem. Pesticide patch test trays should be used in assessing skin diseases in highly exposed workers.
Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso
2016-01-01
The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards.
Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso
2016-01-01
The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user’s loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards. PMID:27907134
Piñero, David P; Plaza, Ana Belén; Alió, Jorge L
2008-01-01
To determine the interchangeability of 2 anterior segment imaging systems: a very-high-frequency (VHF) ultrasound scanning system (Artemis 2, Ultralink LLC) and an optical coherence tomography (OCT) system (Visante, Zeiss). Vissum Instituto Oftalmologico de Alicante, Alicante, Spain. This study comprised 20 eyes without pathology or previous surgery. The anterior chamber depth (ACD), central corneal thickness (CCT), angle-to-angle distance (ATA), and the iridocorneal angle size (IAS) at the 0-degree and 180-degree positions were measured with 2 imaging techniques: VHF ultrasound scanning and OCT. Analysis of agreement and interchangeability was performed by the Bland and Altman method. In addition, each measurement was performed 3 times consecutively to determine intrasession repeatability by means of the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). No statistically significant differences were found between imaging techniques in ACD, CCT, or ATA (P>.40). The ranges of agreement were 0.20 mm, 16.11 mum, and 0.80 mm for ACD, CCT, and ATA, respectively. Regarding IAS, no statistically significant differences were found in the nasal (P = .78) or temporal (P = .63) measurements between devices. However, the range of agreement for nasal (14.3 degrees) and temporal (14.90 degrees) values was relevant, indicating the 2 techniques cannot be used interchangeably for IAS measurement. Excellent intrasession repeatability scores were obtained (CV and ICC). The Artemis 2 and the Visante OCT systems provide equivalent and repeatable measurements of the ACD, CCT, and ATA and can be used interchangeably for these purposes.
Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei
2015-01-01
During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725
[Facing a dilemma in elderly complex and vulnerable patients: to stop or not to stop prevention?
Llobet Vila, Laura; Manresa Domínguez, Josep Maria; Carmona Segado, José Manuel; Franzi Sisó, Alícia; Vallès Balasch, Rosa; Martínez Díaz, Isabel
2017-12-05
1-To know the preventive prescription (statin, antiplatelet drugs, bisphosphonates, calcium and vitamin D and Vit B12) of elderly patients previously identified as a CCD (with a complex chronic disease) and ACD (with advanced chronic disease and lifetime expectancy of less than 12 months) who died during 2015. 2-To assess the correct indication of Proton Pump Inhibitors (PPI) to determine potentially avoidable medication. Retrospective observational study. Four Primary Health Centres, Castellar del Vallès (Barcelona). 128 patients, 70 ACD and 58 PCC. Number of drugs at the time of death from the 6 selected group, deprescription (6 months prior to death due to advanced chronic disease), primary or secondary prevention and inappropriate prescription of PPI. Average age of 85'3 years (10,3). 40% took an antiplatelet drug, avoidable in 60% of the ACD, since they did not present any previous cardiovascular episode. 20% of the patients took statins, in which 48% of the cases were primary prevention. The PPI prescription was 67% with inadequate indication for use in 49% of these cases. 20% took calcium / Vitamin D and 1,6% of the ACD a bisphosphonate. There was a 16% deprescription. A high percentage of our patients with advanced chronic disease and short life expectancy still continue to take preventive and avoidable treatments, potentially dangerous due to their side effects. There is a need to reflect on what we do with these vulnerable patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Biometric Changes After Trabeculectomy with Contact and Non-contact Biometry.
Alvani, Azam; Pakravan, Mohammad; Esfandiari, Hamed; Yaseri, Mehdi; Yazdani, Shahin; Ghahari, Elham
2016-02-01
To compare biometric changes measured with contact and noncontact methods after mitomycin-C-augmented trabeculectomy. In this prospective study, 31 eyes from 31 glaucoma patients scheduled for primary trabeculectomy were enrolled. Biometric parameters including axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) were measured using contact ultrasound biometry (UD-6000 Ultrasonic A/B scanner biometer; Tomey Corporation, Nagoya, Japan) and a noncontact optical biometry device (Lenstar; Haag-Streit AG, Koeniz, Switzerland). Measurements were taken the day before trabeculectomy and then compared with measurements obtained 3 and 6 months after surgery. The AL and ACD were significantly decreased at 3 and 6 months compared with baseline values taken with each biometry method. There was a significant increase in LT measured by the Lenstar device at the 3- and 6-month follow-up. At both the 3- and 6-month follow-up, the mean AL measurement reduction with the Lenstar device was significantly lower than that of the A-scan ultrasound measurements. The mean ACD changes between the two devices were not significantly different. There is a small but significant decrease in the AL and ACD after trabeculectomy as measured with both the contact and noncontact methods. The amount of AL reduction measured is significantly smaller using the noncontact method, making it the preferable method for intraocular lens power calculation for patients who need cataract surgery combined with or after trabeculectomy. The LT measured by the Lenstar device increased significantly after the operation, which can be an early sign of the progression of cataractous changes after trabeculectomy.
The role of backward cell migration in two-hit mutants' production in the stem cell niche.
Bollas, Audrey; Shahriyari, Leili
2017-01-01
It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell's divisions are asymmetric.
Ahmad, Shaad M.; Tansey, Terese R.; Busser, Brian W.; Nolte, Michael T.; Jeffries, Neal; Gisselbrecht, Stephen S.; Rusan, Nasser M.; Michelson, Alan M.
2012-01-01
SUMMARY The development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic and computational strategy for identifying genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor, and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis. PMID:22814603
Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A; Kiebler, Michael; Temple, Sally
2012-10-05
Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs. Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function. Copyright © 2012 Elsevier Inc. All rights reserved.
Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A.; Kiebler, Michael; Temple, Sally
2012-01-01
Summary Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2+ neuroblast daughter, taking with it a sub-set of RNAs. Knockdown of Stau2 stimulates differentiation and over-expression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified novel candidates, including a subset involved in primary cilium function. PMID:22902295
DELAY OF CLEAVAGE OF THE ARBACIA EGG BY ULTRAVIOLET RADIATION
Blum, Harold F.; Price, Judith P.
1950-01-01
While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells. PMID:15410486
Lipid Cell Biology: A Focus on Lipids in Cell Division.
Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S
2018-06-20
Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.
Characterization of a highly efficient chevron-shaped anti-contamination device
NASA Astrophysics Data System (ADS)
Fiore, M.; Vermeersch, O.; Forte, M.; Casalis, G.; François, C.
2016-04-01
This paper is devoted to the characterization of an optimized chevron-shaped anti-contamination device (ACD). This device can prevent efficiently the propagation of turbulence from the fuselage along the attachment line (hypothetical streamline that spreads the flow going to suction side and the one going to pressure side) of swept wings and enables the development of a new laminar boundary layer downstream. More specifically, the aim is to prevent boundary-layer transition along the attachment line by a contamination process. This process is characterized by the typical Reynolds number overline{R} and the associated Poll's criterion. Thus, ACD efficiency will be expressed in terms of overline{R} values. Some experiments performed on a new numerically optimized ACD have shown its ability to prevent leading-edge contamination up to overline{R} values close to the natural transition process of the laminar boundary layer along the attachment line. The corresponding stability analysis of the laminar boundary layer is made using the Görtler-Hämmerlin stability approach. The study is completed with the different transition processes that can occur downstream the attachment line, around the airfoil, especially with crossflow analysis.
Patch testing custom isocyanate materials from the workplace.
Burrows, Dianne; Houle, Marie-Claude; Holness, D Linn; DeKoven, Joel; Skotnicki, Sandy
2015-01-01
Patch testing with standard trays of commercially available allergens is the current practice for investigating suspected cases of isocyanate-induced allergic contact dermatitis (ACD). In some facilities, these standard trays are further supplemented with custom preparations of isocyanate-containing materials. The aim was to determine whether added value exists in patch testing patients to custom isocyanate preparations in suspected cases of ACD. We performed a retrospective analysis of 11 patients referred to our specialty clinic between January 2003 and March 2011 for suspected patients of ACD who had custom testing with isocyanate materials from their workplace. In addition to standard trays of allergens, all patients were patch tested with custom isocyanate materials from their workplaces. Three (27%) of 11 patients showed an added value in testing to custom isocyanate allergens. Of these 3 patients, one had a reaction that reinforced positive reactions to the standard isocyanate tray, but the other 2 (18%) had no reactions to any of the commercially available allergens. Because of the high proportion of reactions (27%), we recommend the use of custom testing to workplace isocyanate products as a supplement to current standard patch testing procedures.
Soltani, Mohammad; Vargas-Garcia, Cesar A.; Antunes, Duarte; Singh, Abhyudai
2016-01-01
Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between two daughter cells are significant. We derive analytical formulas for the total noise in protein levels when the cell-cycle duration follows a general class of probability distributions. Using a novel hybrid approach the total noise is decomposed into components arising from i) stochastic expression; ii) partitioning errors at the time of cell division and iii) random cell-division events. These formulas reveal that random cell-division times not only generate additional extrinsic noise, but also critically affect the mean protein copy numbers and intrinsic noise components. Counter intuitively, in some parameter regimes, noise in protein levels can decrease as cell-division times become more stochastic. Computations are extended to consider genome duplication, where transcription rate is increased at a random point in the cell cycle. We systematically investigate how the timing of genome duplication influences different protein noise components. Intriguingly, results show that noise contribution from stochastic expression is minimized at an optimal genome-duplication time. Our theoretical results motivate new experimental methods for decomposing protein noise levels from synchronized and asynchronized single-cell expression data. Characterizing the contributions of individual noise mechanisms will lead to precise estimates of gene expression parameters and techniques for altering stochasticity to change phenotype of individual cells. PMID:27536771
Localization of FtsZ in Helicobacter pylori and Consequences for Cell Division
Specht, Mara; Dempwolff, Felix; Schätzle, Sarah; Thomann, Ralf
2013-01-01
Of the various kinds of cell division, the most common mode is binary fission, the division of a cell into two morphologically identical daughter cells. However, in the case of asymmetric cell division, Caulobacter crescentus produces two morphologically and functionally distinct cell types. Here, we have studied cell cycle progression of the human pathogen Helicobacter pylori using a functional green fluorescent protein (GFP) fusion of FtsZ protein and membrane staining. In small cells, representing newly divided cells, FtsZ localizes to a single cell pole. During the cell cycle, spiral intermediates are formed until an FtsZ ring is positioned with very little precision, such that central as well as acentral rings can be observed. Daughter cells showed considerably different sizes, suggesting that H. pylori divides asymmetrically. Fluorescence recovery after photobleaching (FRAP) analyses demonstrate that the H. pylori FtsZ ring is about as dynamic as that of Escherichia coli but that polar assemblies show less turnover. Strikingly, our results demonstrate that H. pylori cell division follows a different route from that in E. coli and Bacillus subtilis. It is also different from that in C. crescentus, where cytokinesis regulation proteins like MipZ play a role. Therefore, this report provides the first cell-biological analysis of FtsZ dynamics in the human pathogen H. pylori and even in epsilonproteobacteria to our knowledge. In addition, analysis of the filament architecture of H. pylori and E. coli FtsZ filaments in the heterologous system of Drosophila melanogaster S2 Schneider cells revealed that both have different filamentation properties in vivo, suggesting a unique intrinsic characteristic of each protein. PMID:23335414
The role of backward cell migration in two-hit mutants’ production in the stem cell niche
Bollas, Audrey
2017-01-01
It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell’s divisions are asymmetric. PMID:28931019
Lipka, Elisabeth; Gadeyne, Astrid; Stöckle, Dorothee; Zimmermann, Steffi; De Jaeger, Geert; Ehrhardt, David W.; Kirik, Viktor; Van Damme, Daniel; Müller, Sabine
2014-01-01
The preprophase band (PPB) is a faithful but transient predictor of the division plane in somatic cell divisions. Throughout mitosis the PPBs positional information is preserved by factors that continuously mark the division plane at the cell cortex, the cortical division zone, by their distinct spatio-temporal localization patterns. However, the mechanism maintaining these identity factors at the plasma membrane after PPB disassembly remains obscure. The pair of kinesin-12 class proteins PHRAGMOPLAST ORIENTING KINESIN1 (POK1) and POK2 are key players in division plane maintenance. Here, we show that POK1 is continuously present at the cell cortex, providing a spatial reference for the site formerly occupied by the PPB. Fluorescence recovery after photobleaching analysis combined with microtubule destabilization revealed dynamic microtubule-dependent recruitment of POK1 to the PPB during prophase, while POK1 retention at the cortical division zone in the absence of cortical microtubules appeared static. POK function is strictly required to maintain the division plane identity factor TANGLED (TAN) after PPB disassembly, although POK1 and TAN recruitment to the PPB occur independently during prophase. Together, our data suggest that POKs represent fundamental early anchoring components of the cortical division zone, translating and preserving the positional information of the PPB by maintaining downstream identity markers. PMID:24972597
Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H
2016-01-01
Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.
Ansalone, Cecilia; Utriainen, Lotta; Milling, Simon; Goodyear, Carl S
2017-09-01
To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system in the pathogenesis of HLA-B27-associated spondyloarthritis using an HLA-B27-transgenic (B27-Tg) rat model. The myeloid compartment of the blood and bone marrow (BM) of B27-Tg rats, as well as HLA-B7-Tg and non-Tg rats as controls, was evaluated by flow cytometry. Plasma from rats was assessed by enzyme-linked immunosorbent assay for levels of CCL2 and interleukin-1α (IL-1α). Rats were treated with antibiotics for 4 weeks, and the myeloid compartment of the blood and BM was evaluated by flow cytometry. The osteoclastogenic potential of BM-derived cells from antibiotic-treated rats, in the presence or absence of tumor necrosis factor (TNF), was evaluated in vitro. B27-Tg rats had substantially higher numbers of circulating Lin-CD172a+CD43 low monocytes as compared to control animals, and this was significantly correlated with higher levels of plasma CCL2. Antibiotic treatment of B27-Tg rats markedly reduced the severity of ileitis, plasma levels of CCL2 and IL-1α, and number of BM and blood Lin-CD172a+CD43 low monocytes, a cell subset shown in the present study to have the greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented the TNF-dependent enhancement of osteoclastogenesis in B27-Tg rats. Microbiota-dependent intestinal inflammation in B27-Tg rats directly drives the systemic inflammatory and bone-erosive potential of the monocyte compartment. © 2017, American College of Rheumatology.