The Fate of a Normal Human Cell Traversed by a Single Charged Particle

Science.gov (United States)

Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

2012-01-01

The long-term “fate” of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability. PMID:22966418

Generalising tree traversals to DAGs

DEFF Research Database (Denmark)

Bahr, Patrick; Axelsson, Emil

2015-01-01

We present a recursion scheme based on attribute grammars that can be transparently applied to trees and acyclic graphs. Our recursion scheme allows the programmer to implement a tree traversal and then apply it to compact graph representations of trees instead. The resulting graph traversals avoid...... is not sound. Therefore, we complement our implementation of the recursion scheme with a number of correspondence theorems that ensure soundness for various classes of traversals. We illustrate the practical applicability of the implementation as well as the complementing theory with a number of examples....

DNA damage does not appear to be a trigger for thermotolerance in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Anderson, R.L.; Shiu, E.; Fisher, G.A.; Hahn, G.M.

1988-08-01

The hypothesis that DNA damage is the trigger for thermotolerance in mammalian cells was tested in Chinese hamster ovary cells by looking for evidence of thermotolerance after ionizing radiation or ultraviolet light exposure. As previous studies have demonstrated that relatively non-toxic radiation exposures do not induce thermotolerance in mammalian cells (Li et al. 1976), higher doses, comparable to those used in yeast to induce thermotolerance (Mitchel and Morison 1984), were tested in this study. Doses of this magnitude are lethal to mammalian cells, thereby precluding the use of clonogenic survival as an endpoint. The authors used three alternative assays as indicators of the subsequent development of thermotolerance: (a) heat-induced inhibition of total protein synthesis, (b) heat-induced uptake of dansyl lysine, and (c) synthesis of heat shock proteins. Only total protein synthesis revealed evidence of a small degree of thermotolerance which occurred immediately after ..gamma..-radiation exposure. By 4 h postirradiation the tolerance, as measured by this assay, was no longer evident. No evidence of thermotolerance was seen following UV exposure. In addition, when a large radiation dose was given either immediately before or after a heat treatment used to induce thermotolerance, there was no alteration in the level of heat-induced tolerance, despite the extensive number of DNA strand breaks caused by the radiation.

DNA damage does not appear to be a trigger for thermotolerance in mammalian cells

International Nuclear Information System (INIS)

Anderson, R.L.; Shiu, E.; Fisher, G.A.; Hahn, G.M.

1988-01-01

The hypothesis that DNA damage is the trigger for thermotolerance in mammalian cells was tested in Chinese hamster ovary cells by looking for evidence of thermotolerance after ionizing radiation or ultraviolet light exposure. As previous studies have demonstrated that relatively non-toxic radiation exposures do not induce thermotolerance in mammalian cells (Li et al. 1976), higher doses, comparable to those used in yeast to induce thermotolerance (Mitchel and Morison 1984), were tested in this study. Doses of this magnitude are lethal to mammalian cells, thereby precluding the use of clonogenic survival as an endpoint. The authors used three alternative assays as indicators of the subsequent development of thermotolerance: (a) heat-induced inhibition of total protein synthesis, (b) heat-induced uptake of dansyl lysine, and (c) synthesis of heat shock proteins. Only total protein synthesis revealed evidence of a small degree of thermotolerance which occurred immediately after γ-radiation exposure. By 4 h postirradiation the tolerance, as measured by this assay, was no longer evident. No evidence of thermotolerance was seen following UV exposure. In addition, when a large radiation dose was given either immediately before or after a heat treatment used to induce thermotolerance, there was no alteration in the level of heat-induced tolerance, despite the extensive number of DNA strand breaks caused by the radiation. (author)

Sensitization of ultraviolet radiation damage in bacteria and mammalian cells

International Nuclear Information System (INIS)

Fisher, G.J.; Watts, M.E.; Patel, K.B.; Adams, G.E.

1978-01-01

Bacteria (Serratia marcescens) and mammalian cells (Chinese hamsters V79-379A) were irradiated in monolayers with ultraviolet light at 254 nm or 365 nm in the presence or absence of radiosensitizing drugs. At 254 nm, killing is very efficient (Dsub(37) approximately equal 1 J m -2 exposure, or approximately equal 6 x 10 4 photons absorbed by DNA per bacterium), and sensitizers have no effect. At 365 nm, cells are not killed in buffer, but are inactivated in the presence of nifurpipone or misonidazole. Lethal exposures (approximately equal 5 x 10 3 J m -2 at 10 nM misonidazole) correspond to about 10 7 photons absorbed by sensitizer molecules per bacterium. Toxicity of stable photoproducts of the drugs is not involved, nor is oxygen required. Hence the transient species formed by photo-excitation of radiosensitizer molecules are capable of killing cells in the absence of other types of radiation damage. (author)

RTSAH Traversal Order for Occlusion Rays

KAUST Repository

Ize, Thiago

2011-04-01

We accelerate the finding of occluders in tree based acceleration structures, such as a packetized BVH and a single ray kd-tree, by deriving the ray termination surface area heuristic (RTSAH) cost model for traversing an occlusion ray through a tree and then using the RTSAH to determine which child node a ray should traverse first instead of the traditional choice of traversing the near node before the far node. We further extend RTSAH to handle materials that attenuate light instead of fully occluding it, so that we can avoid superfluous intersections with partially transparent objects. For scenes with high occlusion, we substantially lower the number of traversal steps and intersection tests and achieve up to 2× speedups. © 2010 The Author(s).

RTSAH Traversal Order for Occlusion Rays

KAUST Repository

Ize, Thiago; Hansen, Charles

2011-01-01

We accelerate the finding of occluders in tree based acceleration structures, such as a packetized BVH and a single ray kd-tree, by deriving the ray termination surface area heuristic (RTSAH) cost model for traversing an occlusion ray through a tree and then using the RTSAH to determine which child node a ray should traverse first instead of the traditional choice of traversing the near node before the far node. We further extend RTSAH to handle materials that attenuate light instead of fully occluding it, so that we can avoid superfluous intersections with partially transparent objects. For scenes with high occlusion, we substantially lower the number of traversal steps and intersection tests and achieve up to 2× speedups. © 2010 The Author(s).

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

International Nuclear Information System (INIS)

Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

1991-02-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

Science.gov (United States)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

Conformally symmetric traversable wormholes

International Nuclear Information System (INIS)

Boehmer, Christian G.; Harko, Tiberiu; Lobo, Francisco S. N.

2007-01-01

Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at a finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced

P-CSCF's Algorithm for Solving NAT Traversal

Science.gov (United States)

Kim, Jung-Ho; Cho, Jae-Hyoung; Lee, Jae-Oh

Many ways for efficient use of limited IP address of IPv4 are existed. The one of these ways is to construct the private network using Network Address Translator (NAT). NAT filtering rule makes network management easier. However, NAT Filtering rule makes NAT Traversal. Many solutions like Simple Traversal of UDP through NAT (STUN), Traversal Using Relay NAT (TURN) and Media Relay method exist. But these solutions require additional servers or devices. So, we suggest that P-CSCFs in the IP Multimedia Subsystem (IMS) change the packet's header and solve the NAT Traversal without any additional equipment.

Mycobacterium tuberculosis Ku can bind to nuclear DNA damage and sensitize mammalian cells to bleomycin sulfate.

Science.gov (United States)

Castore, Reneau; Hughes, Cameron; Debeaux, Austin; Sun, Jingxin; Zeng, Cailing; Wang, Shih-Ya; Tatchell, Kelly; Shi, Runhua; Lee, Kyung-Jong; Chen, David J; Harrison, Lynn

2011-11-01

Radiotherapy and chemotherapy are effective cancer treatments due to their ability to generate DNA damage. The major lethal lesion is the DNA double-strand break (DSB). Human cells predominantly repair DSBs by non-homologous end joining (NHEJ), which requires Ku70, Ku80, DNA-PKcs, DNA ligase IV and accessory proteins. Repair is initiated by the binding of the Ku heterodimer at the ends of the DSB and this recruits DNA-PKcs, which initiates damage signaling and functions in repair. NHEJ also exists in certain types of bacteria that have dormant phases in their life cycle. The Mycobacterium tuberculosis Ku (Mt-Ku) resembles the DNA-binding domain of human Ku but does not have the N- and C-terminal domains of Ku70/80 that have been implicated in binding mammalian NHEJ repair proteins. The aim of this work was to determine whether Mt-Ku could be used as a tool to bind DSBs in mammalian cells and sensitize cells to DNA damage. We generated a fusion protein (KuEnls) of Mt-Ku, EGFP and a nuclear localization signal that is able to perform bacterial NHEJ and hence bind DSBs. Using transient transfection, we demonstrated that KuEnls is able to bind laser damage in the nucleus of Ku80-deficient cells within 10 sec and remains bound for up to 2 h. The Mt-Ku fusion protein was over-expressed in U2OS cells and this increased the sensitivity of the cells to bleomycin sulfate. Hydrogen peroxide and UV radiation do not predominantly produce DSBs and there was little or no change in sensitivity to these agents. Since in vitro studies were unable to detect binding of Mt-Ku to DNA-PKcs or human Ku70/80, this work suggests that KuEnls sensitizes cells by binding DSBs, preventing human NHEJ. This study indicates that blocking or decreasing the binding of human Ku to DSBs could be a method for enhancing existing cancer treatments.

Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

Science.gov (United States)

Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

2014-01-01

Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to

Induced vibrations facilitate traversal of cluttered obstacles

Science.gov (United States)

Thoms, George; Yu, Siyuan; Kang, Yucheng; Li, Chen

When negotiating cluttered terrains such as grass-like beams, cockroaches and legged robots with rounded body shapes most often rolled their bodies to traverse narrow gaps between beams. Recent locomotion energy landscape modeling suggests that this locomotor pathway overcomes the lowest potential energy barriers. Here, we tested the hypothesis that body vibrations induced by intermittent leg-ground contact facilitate obstacle traversal by allowing exploration of locomotion energy landscape to find this lowest barrier pathway. To mimic a cockroach / legged robot pushing against two adjacent blades of grass, we developed an automated robotic system to move an ellipsoidal body into two adjacent beams, and varied body vibrations by controlling an oscillation actuator. A novel gyroscope mechanism allowed the body to freely rotate in response to interaction with the beams, and an IMU and cameras recorded the motion of the body and beams. We discovered that body vibrations facilitated body rolling, significantly increasing traversal probability and reducing traversal time (P locomotor pathways in complex 3-D terrains.

Damage and repair in mammalian cells after ultraviolet and/or visible light treatment

International Nuclear Information System (INIS)

Harm, H.

1976-01-01

Ultraviolet (uv) light (254 nm or 302 nm) was used to induce lesions in DNA of cultured mammalian cells in vivo, particularly in fibroblasts from potoroo cornea, mouse skin (3T3), cat cornea, human skin (healthy and diseased), and in freshly obtained ox cornea tissue. In addition, white light (WL) from daylight fluorescent lamps, filtered through a plexiglass plate cutting off virtually all photons less than 380 nm and being fully transparent for greater than 400 nm, was applied in vivo either as photoreactivating light after uv irradiation, or as damaging radiation by itself. Completely unirradiated samples under otherwise identical conditions served as controls. DNA from cells exposed to these different radiations was extracted and tested for its capability of competitively inhibiting photoenzymatic repair of uv-irradiated Haemophilus influenzae transforming DNA in vitro in the presence of yeast photoreactivating enzyme (PRE) and photoreactivating light. In several (but not all) of the cases, DNA from cells treated with uv + WL displayed considerably less competitive inhibition than DNA from cells treated with uv alone, even though under certain conditions WL itself caused damage serving as substrate from the PRE in vitro. Cell cultures differing in their origin or in their number of passages varied substantially in this respect

RBE-LET relationships for different types of lethal radiation damage in mammalian cells: comparison with DNA dsb and an interpretation of differences in radiosensitivity

NARCIS (Netherlands)

Barendsen, G. W.

1994-01-01

Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents

Transient field for W ions traversing Fe hosts and for Os ions traversing Fe and Ni hosts

International Nuclear Information System (INIS)

Stuchbery, A.E.; Bolotin, H.H.; Doran, C.E.

1987-02-01

Transient field strengths were measured for 184 W and 186 W ions traversing thin, magnetized Fe foils with velocities in the range 1.8 ≤ v/v>=o ≤ 5.7 (v>=o Bohr velocity) and for 188 Os, 190 Os, 192 Os ions traversing polarized Ni hosts with average velocities =o> ∼ 4. The present measured transient field strengths, together with previously measured results for W, Os ions, are compared with transient-field strength parametrizations, and discussed in terms of microscopic models of the transient field

Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

Science.gov (United States)

Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

2013-01-01

Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

Training Revising Based Traversability Analysis of Complex Terrains for Mobile Robot

Directory of Open Access Journals (Sweden)

Rui Song

2014-05-01

Full Text Available Traversability analysis is one of the core issues in the autonomous navigation for mobile robots to identify the accessible area by the information of sensors on mobile robots. This paper proposed a model to analyze the traversability of complex terrains based on rough sets and training revising. The model described the traversability for mobile robots by traversability cost. Through the experiment, the paper gets the conclusion that traversability analysis model based on rough sets and training revising can be used where terrain features are rich and complex, can effectively handle the unstructured environment, and can provide reliable and effective decision rules in the autonomous navigation for mobile robots.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

Science.gov (United States)

Ogrodnik, Mikołaj; Salmonowicz, Hanna; Brown, Rachel; Turkowska, Joanna; Średniawa, Władysław; Pattabiraman, Sundararaghavan; Amen, Triana; Abraham, Ayelet-chen; Eichler, Noam; Lyakhovetsky, Roman; Kaganovich, Daniel

2014-06-03

Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells. Here, we demonstrate, using long-term 4D imaging, that the vimentin intermediate filament establishes mitotic polarity in mammalian cell lines and mediates the asymmetric partitioning of damaged proteins. We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins are inherited asymmetrically, similarly to JUNQ quality-control inclusions observed in yeast. Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by the same cell as the JUNQ. Our study suggests that the mammalian cytoskeleton and intermediate filaments provide the physical scaffold for asymmetric inheritance of dynamic quality-control JUNQ inclusions. Mammalian IPOD inclusions containing amyloidogenic proteins are not partitioned as effectively during mitosis as their counterparts in yeast. These findings provide a valuable mechanistic basis for studying the process of asymmetric inheritance in mammalian cells, including cells potentially undergoing polar divisions, such as differentiating stem cells and cancer cells.

Regulation of gene expression in mammalian cells following ionizing radiation

International Nuclear Information System (INIS)

Boothman, D.A.; Lee, S.W

1991-01-01

Mammalian cells use a variety of mechanisms to control the expression of new gene transcrips elicited in response to ionizing radiation. Damage-induced proteins have been found which contain DNA binding sites located within the promoter regions of SV40 and human thymidine kinase genes. DNA binding proteins as well as proteins which bind to specific DNA lesions (e.g., XIP bp 175 binds specifically to X-ray-damaged DNA) may play a role in the initial recognition of DNA damage and may initiate DNA repair processes, along with new transcription. Mammalian gene expression after DNA damage is also regulated via the stabilization of preexisting mRNA transcripts. Stabilized mRNA transcripts are translated into protein products not previously present in the cell due to undefined posttranscriptional modifications. Thus far, the only example of mRNA stabilization following X-irradiation is the immediate induction of tissue-type plasminogen activator. Mammalian cells synthesize new mRNA transcripts indirect response to DNA damage. Using cDNA cloning, Northern RNA blotting and nuclear run-on techniques, the levels of a variety of known and previously unknown genes dramatically increase following X-irradiation. These genes/proteins now include; a) DNA binding transcripts factors, such as the UV-responsive element binding factors, ionizing radiation-induced DNA-binding proteins, and XIP bP 175; b) proto-oncogenes, such as c-fos, c-jun, and c-myc; c) several growth-related genes, (e.g., the gadd genes, protein kinase C, IL-1, and thymidine kinase); and d) a variety of other genes, including proteases, tumor necrosis factor-alpha, and DT diaphorase. Mammalian cells respond to X-irradiation by eliciting a very complex series of events resulting in the appearance of new genes and proteins. These gene products may affect DNA repair, adaptive responses, apoptosis, SOS-type mutagenic response, and/or carcinogenesis. (J.P.N.)

Comparison of pitot traverses taken at varying distances downstream of obstructions.

Science.gov (United States)

Guffey, S E; Booth, D W

1999-01-01

This study determined the deviations between pitot traverses taken under "ideal" conditions--at least seven duct diameter's lengths (i.e., distance = 7D) from obstructions, elbows, junction fittings, and other disturbances to flows--with those taken downstream from commonplace disturbances. Two perpendicular 10-point, log-linear velocity pressure traverses were taken at various distances downstream of tested upstream conditions. Upstream conditions included a plain duct opening, a junction fitting, a single 90 degrees elbow, and two elbows rotated 90 degrees from each other into two orthogonal planes. Airflows determined from those values were compared with the values measured more than 40D downstream of the same obstructions under ideal conditions. The ideal measurements were taken on three traverse diameters in the same plane separated by 120 degrees in honed drawn-over-mandrel tubing. In all cases the pitot tubes were held in place by devices that effectively eliminated alignment errors and insertion depth errors. Duct velocities ranged from 1500 to 4500 ft/min. Results were surprisingly good if one employed two perpendicular traverses. When the averages of two perpendicular traverses was taken, deviations from ideal value were 6% or less even for traverses taken as close as 2D distance from the upstream disturbances. At 3D distance, deviations seldom exceeded 5%. With single diameter traverses, errors seldom exceeded 5% at 6D or more downstream from the disturbance. Interestingly, percentage deviations were about the same at high and low velocities. This study demonstrated that two perpendicular pitot traverses can be taken as close as 3D from these disturbances with acceptable (< or = 5%) deviations from measurements taken under ideal conditions.

Traversal Caches: A Framework for FPGA Acceleration of Pointer Data Structures

Directory of Open Access Journals (Sweden)

James Coole

2010-01-01

Full Text Available Field-programmable gate arrays (FPGAs and other reconfigurable computing (RC devices have been widely shown to have numerous advantages including order of magnitude performance and power improvements compared to microprocessors for some applications. Unfortunately, FPGA usage has largely been limited to applications exhibiting sequential memory access patterns, thereby prohibiting acceleration of important applications with irregular patterns (e.g., pointer-based data structures. In this paper, we present a design pattern for RC application development that serializes irregular data structure traversals online into a traversal cache, which allows the corresponding data to be efficiently streamed to the FPGA. The paper presents a generalized framework that benefits applications with repeated traversals, which we show can achieve between 7x and 29x speedup over pointer-based software. For applications without strictly repeated traversals, we present application-specialized extensions that benefit applications with highly similar traversals by exploiting similarity to improve memory bandwidth and execute multiple traversals in parallel. We show that these extensions can achieve a speedup between 11x and 70x on a Virtex4 LX100 for Barnes-Hut n-body simulation.

Traversable Schwarzschild-like wormholes

Energy Technology Data Exchange (ETDEWEB)

Cataldo, Mauricio [Universidad del Bio-Bio, Departamento de Fisica, Facultad de Ciencias, Concepcion (Chile); Grupo de Cosmologia y Gravitacion-UBB, Concepcion (Chile); Liempi, Luis [Universidad de Concepcion, Departamento de Fisica, Concepcion (Chile); Universidad San Sebastian, Facultad de Ingenieria y Tecnologia, Concepcion (Chile); Rodriguez, Pablo [Universidad de Concepcion, Departamento de Fisica, Concepcion (Chile)

2017-11-15

In this paper we study relativistic static traversable wormhole solutions which are a slight generalization of Schwarzschild wormholes. In order to do this we assume a shape function with a linear dependence on the radial coordinate r. This linear shape function generates wormholes whose asymptotic spacetime is not flat: they are asymptotically locally flat, since in the asymptotic limit r → ∞ spacetimes exhibiting a solid angle deficit (or excess) are obtained. In particular, there exist wormholes which connect two asymptotically non-flat regions with a solid angle deficit. For these wormholes the size of their embeddings in a three-dimensional Euclidean space extends from the throat to infinity. A new phantom zero-tidal-force wormhole exhibiting such asymptotic is obtained. On the other hand, if a solid angle excess is present, the size of the wormhole embeddings depends on the amount of this angle excess, and the energy density is negative everywhere. We discuss the traversability conditions and study the impact of the β-parameter on the motion of a traveler when the wormhole throat is crossed. A description of the geodesic behavior for the wormholes obtained is also presented. (orig.)

Traversable Schwarzschild-like wormholes

International Nuclear Information System (INIS)

Cataldo, Mauricio; Liempi, Luis; Rodriguez, Pablo

2017-01-01

In this paper we study relativistic static traversable wormhole solutions which are a slight generalization of Schwarzschild wormholes. In order to do this we assume a shape function with a linear dependence on the radial coordinate r. This linear shape function generates wormholes whose asymptotic spacetime is not flat: they are asymptotically locally flat, since in the asymptotic limit r → ∞ spacetimes exhibiting a solid angle deficit (or excess) are obtained. In particular, there exist wormholes which connect two asymptotically non-flat regions with a solid angle deficit. For these wormholes the size of their embeddings in a three-dimensional Euclidean space extends from the throat to infinity. A new phantom zero-tidal-force wormhole exhibiting such asymptotic is obtained. On the other hand, if a solid angle excess is present, the size of the wormhole embeddings depends on the amount of this angle excess, and the energy density is negative everywhere. We discuss the traversability conditions and study the impact of the β-parameter on the motion of a traveler when the wormhole throat is crossed. A description of the geodesic behavior for the wormholes obtained is also presented. (orig.)

DNA damage-inducible transcripts in mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Alamo, I. Jr.; Hollander, M.C.

1988-01-01

Hybridization subtraction at low ratios of RNA to cDNA was used to enrich for the cDNA of transcripts increased in Chinese hamster cells after UV irradiation. Forty-nine different cDNA clones were isolated. Most coded for nonabundant transcripts rapidly induced 2- to 10-fold after UV irradiation. Only 2 of the 20 cDNA clones sequenced matched known sequences (metallothionein I and II). The predicted amino acid sequence of one cDNA had two localized areas of homology with the rat helix-destabilizing protein. These areas of homology were at the two DNA-binding sites of this nucleic acid single-strand-binding protein. The induced transcripts were separated into two general classes. Class I transcripts were induced by UV radiation and not by the alkylating agent methyl methanesulfonate. Class II transcripts were induced by UV radiation and by methyl methanesulfonate. Many class II transcripts were induced also by H2O2 and various alkylating agents but not by heat shock, phorbol 12-tetradecanoate 13-acetate, or DNA-damaging agents which do not produce high levels of base damage. Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury

Message passing with parallel queue traversal

Science.gov (United States)

Underwood, Keith D [Albuquerque, NM; Brightwell, Ronald B [Albuquerque, NM; Hemmert, K Scott [Albuquerque, NM

2012-05-01

In message passing implementations, associative matching structures are used to permit list entries to be searched in parallel fashion, thereby avoiding the delay of linear list traversal. List management capabilities are provided to support list entry turnover semantics and priority ordering semantics.

DNA repair and radiation sensitivity in mammalian cells

International Nuclear Information System (INIS)

Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

1993-01-01

Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

Science.gov (United States)

Felder, Michael; Nesnas, Issa A.; Pivtoraiko, Mihail; Kelly, Alonzo; Volpe, Richard

2011-01-01

Exploring planetary surfaces typically involves traversing challenging and unknown terrain and acquiring in-situ measurements at designated locations using arm-mounted instruments. We present field results for a new implementation of an autonomous capability that enables a rover to traverse and precisely place an arm-mounted instrument on remote targets. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover's mast cameras. The rover then autonomously traverse the rocky terrain for a distance of 10 - 15 m, tracks the target(s) of interest during the traverse, positions itself for approaching the target, and then precisely places an arm-mounted instrument within 2-3 cm from the originally designated target. The rover proceeds to acquire science measurements with the instrument. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight thread-the-needle maneuvers. We integrated these algorithms on the newly refurbished Athena Mars research rover and fielded them in the JPL Mars Yard. We conducted 43 runs with targets at distances ranging from 5 m to 15 m and achieved a success rate of 93% for placement of the instrument within 2-3 cm.

Generalising tree traversals and tree transformations to DAGs

DEFF Research Database (Denmark)

Bahr, Patrick; Axelsson, Emil

2017-01-01

We present a recursion scheme based on attribute grammars that can be transparently applied to trees and acyclic graphs. Our recursion scheme allows the programmer to implement a tree traversal or a tree transformation and then apply it to compact graph representations of trees instead. The resul......We present a recursion scheme based on attribute grammars that can be transparently applied to trees and acyclic graphs. Our recursion scheme allows the programmer to implement a tree traversal or a tree transformation and then apply it to compact graph representations of trees instead...... as the complementing theory with a number of examples....

A comprehensive complex systems approach to the study and analysis of mammalian cell cycle control system in the presence of DNA damage stress.

Science.gov (United States)

Abroudi, Ali; Samarasinghe, Sandhya; Kulasiri, Don

2017-09-21

Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other. This retains the functionality of the system and provides a clearer interpretation to the processes within it while reducing the complexity in comprehending these processes. To achieve this, we first update a published ODE mathematical model of cell cycle with current knowledge. Then the part of the mathematical model relevant to each sub-system is shown separately in conjunction with a diagram of the sub-system as part of this representation. The model sub-systems are Growth Factor, DNA damage, G1-S, and G2-M checkpoint signalling. To further simplify the model and better explore the function of sub-systems, they are further divided into modules. Here we also add important new modules of: chk-related rapid cell cycle arrest, p53 modules expanded to seamlessly integrate with the rapid arrest module, Tyrosine phosphatase modules that activate Cyc_Cdk complexes and play a crucial role in rapid and delay arrest at both G1-S and G2-M, Tyrosine Kinase module that is important for inactivating nuclear transport of CycB_cdk1 through Wee1 to resist M phase entry, Plk1-Related module that is crucial in activating Tyrosine phosphatases and inactivating Tyrosine kinase, and APC-Related module to show steps in CycB degradation. This multi-level systems approach incorporating all known aspects of cell cycle allowed us to (i) study, through dynamic simulation of an ODE model

Does autophagy have a license to kill mammalian cells?

NARCIS (Netherlands)

Scarlatti, F.; Granata, R.; Meijer, A. J.; Codogno, P.

2009-01-01

Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the

Meta-analysis of attitudes toward damage-causing mammalian wildlife.

Science.gov (United States)

Kansky, Ruth; Kidd, Martin; Knight, Andrew T

2014-08-01

Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. © 2014 The Authors. Conservation Biology

Membrane phospholipids and radiation-induced death of mammalian cells

International Nuclear Information System (INIS)

Wolters, H.

1987-01-01

Radiation-induced cell killing is generally believed to be a consequence of residual DNA damage or damage that is mis-repaired. However, besides this DNA damage, damage to other molecules or structures of the cell may be involved in the killing. Especially membranes have been suggested as a determinant in cellular radiosensitivity. In this thesis experiments are described, dealing with the possible involvement of membranes in radiation-induced killing of mammalian cells. A general treatise of membrane structure is followed by information concerning deleterious effects of radiation on membranes. Consequences of damage to structure and function of membranes are reviewed. Thereafter evidence relating to the possible involvement of membranes in radiation-induced cell killing is presented. (Auth.)

NAT Traversing Solutions for SIP Applications

Directory of Open Access Journals (Sweden)

Huang Ya-Lin

2008-01-01

Full Text Available Abstract Session Initiation Protocol (SIP has been proposed for multimedia services and wide-area connectivity in smart home environments (SHEs. An important issue for SIP deployment in SHEs is network address translator (NAT traversing. SIP and Real-time Transport Protocol (RTP packets are delivered between an SHE (i.e., private IP network and Internet (i.e., a public IP network through an NAT function of a home gateway, and the NAT translates the IP/transport layer address and port number but leaves the application layer content unchanged. This results in inconsistency between the IP addresses/port numbers in the IP/transport layers and those in the SIP layer. To resolve this issue, we describe six solutions including static route, UPnP, STUN, ICE, ALG, and SBC. Then we compare these solutions in terms of smart home appliance (SHA modification, scope of NATs supported, multilayer NAT traversal, ease of configuration, security issue, and time complexities.

NAT Traversing Solutions for SIP Applications

Directory of Open Access Journals (Sweden)

Han-Chieh Chao

2008-05-01

Full Text Available Session Initiation Protocol (SIP has been proposed for multimedia services and wide-area connectivity in smart home environments (SHEs. An important issue for SIP deployment in SHEs is network address translator (NAT traversing. SIP and Real-time Transport Protocol (RTP packets are delivered between an SHE (i.e., private IP network and Internet (i.e., a public IP network through an NAT function of a home gateway, and the NAT translates the IP/transport layer address and port number but leaves the application layer content unchanged. This results in inconsistency between the IP addresses/port numbers in the IP/transport layers and those in the SIP layer. To resolve this issue, we describe six solutions including static route, UPnP, STUN, ICE, ALG, and SBC. Then we compare these solutions in terms of smart home appliance (SHA modification, scope of NATs supported, multilayer NAT traversal, ease of configuration, security issue, and time complexities.

The influence of oxygen on the induction of radiation damage in DNA in mammalian cells after sensitization by intracellular glutathione depletion

International Nuclear Information System (INIS)

Schans, G.P. van der; Vos, O.; Roos-Verheij, W.S.D.; Lohman, P.H.M.

1986-05-01

Treatment of mammalian cells with buthionine sulphoximine (BSO) or diethyl maleate (DEM) results in a decrease in the intracellular GSH (glutathione) and NPSH (non-protein-bound SH) levels. The effect of depletion of GSH and NPSH on radiosensitivity was studied in relation to the concentration of oxygen during irradiation. Single- and double-strand DNA breaks (ssb and dsb) and cell killing were used as criteria for radiation damage. Under aerobic conditions, BSO and DEM treatment gave a small sensitization of 10-20% for the 3 types of radiation damage. Also under severely hypoxic conditions (0.01 μM oxygen in the medium) the sensitizing effect of both compounds on the induction of ssb and dsb and on cell killing was small (0-30%). At somewhat higher concentrations of oxygen (0.5-10 μM) however, the sensitization amounted to about 90% for the induction of ssb and dsb and about 50% for cell killing. These results strengthen the widely accepted idea that intracellular SH-compounds compete with oxygen and other electron-affinic radiosensitizers with respect to reaction with radiation-induced damage, thus preventing the fixation of DNA damages by oxygen. These results imply that the extent to which SH-compounds affect the radiosensitivity of cells in vivo depends strongly on the local concentration of oxygen. (Auth.)

Breaking the Game: The traversal of the emergent narrative in video games

Directory of Open Access Journals (Sweden)

Pedro Cardoso

2013-12-01

Full Text Available In video games the player’s actions shape the narrative of their personal experience, molding what otherwise would be a linear course. This emergent narrative is in a state of constant transformation, dependent on how the player influences it. This paper explores how the players traverse ergodic media such as video games and how narrative emerges from the interactions between them and the system. In a previous text we have proposed three types of traversal in video games (Cardoso & Carvalhais, 2013: 1 that in which the player has the ability to choose between mutually exclusive paths; 2 that in which the player has the ability to expand the narrative; and 3 that in which the traversal is determined by the disposition of the other actors in the game world towards the player and each other. This paper intends to further contribute by adding another one: 4 a type of traversal that is rooted in the exploitation of any flaws and glitches in the system, allowing the player to traverse the game through an overlooked side of the algorithm, journeying through a world of unpredictable behaviours and events, that may ultimately break the game altogether.  

NAT Traversal Capability and Keep-Alive Functionality with IPSec in IKEv2 Implementation

OpenAIRE

CHAMAN SINGH; K.L.BANSAL

2012-01-01

Since IPv4 Private Networks are behind NAT (Network Address Translation) devices. So, to bypass the Binding Update and Binding Acknowledgment by NAT, we need to encapsulate it in UDP (User datagram Protocol) Packets. Hence, the Dual Stack Mobile IPv6 should support NAT Traversal and Detection. So for proper securing and fully functionality of NAT traversal, it should be IP Security Protected. Paper presents design and implementation of NAT traversal capability and keeps alive functionality wi...

Traversing the Fantasy of the Heroic Entrepreneur

DEFF Research Database (Denmark)

Garmann Johnsen, Christian; Meier Sørensen, Bent

2017-01-01

Purpose: While considerable critical energy has been devoted to unmasking the figure of the heroic entrepreneur, the idea that entrepreneurs are unique individuals with special abilities continues to be widespread in scholarly research, social media and popular culture. The purpose of this paper...... is to traverse the fantasy of the heroic entrepreneur by offering a reading of Richard Branson’s autobiography, Losing My Virginity. Design/methodology/approach: The theoretical approach of this paper is informed by Slavoj Žižek’s concept of fantasy and his critical analytical strategy of “traversing the fantasy......”. Žižek offers a theoretical framework that allows us to understand how narratives of famous entrepreneurs create paradoxical fantasies that produce desire. Findings: By offering a reading of Richard Branson’s autobiography, Losing My Virginity, this paper serves to illustrate how the fantasy...

Traversable geometric dark energy wormholes constrained by astrophysical observations

Energy Technology Data Exchange (ETDEWEB)

Wang, Deng [Nankai University, Theoretical Physics Division, Chern Institute of Mathematics, Tianjin (China); Meng, Xin-he [Nankai University, Department of Physics, Tianjin (China); Institute of Theoretical Physics, CAS, State Key Lab of Theoretical Physics, Beijing (China)

2016-09-15

In this paper, we introduce the astrophysical observations into the wormhole research. We investigate the evolution behavior of the dark energy equation of state parameter ω by constraining the dark energy model, so that we can determine in which stage of the universe wormholes can exist by using the condition ω < -1. As a concrete instance, we study the Ricci dark energy (RDE) traversable wormholes constrained by astrophysical observations. Particularly, we find from Fig. 5 of this work, when the effective equation of state parameter ω{sub X} < -1 (or z < 0.109), i.e., the null energy condition (NEC) is violated clearly, the wormholes will exist (open). Subsequently, six specific solutions of statically and spherically symmetric traversable wormhole supported by the RDE fluids are obtained. Except for the case of a constant redshift function, where the solution is not only asymptotically flat but also traversable, the five remaining solutions are all non-asymptotically flat, therefore, the exotic matter from the RDE fluids is spatially distributed in the vicinity of the throat. Furthermore, we analyze the physical characteristics and properties of the RDE traversable wormholes. It is worth noting that, using the astrophysical observations, we obtain the constraints on the parameters of the RDE model, explore the types of exotic RDE fluids in different stages of the universe, limit the number of available models for wormhole research, reduce theoretically the number of the wormholes corresponding to different parameters for the RDE model, and provide a clearer picture for wormhole investigations from the new perspective of observational cosmology. (orig.)

Traversable geometric dark energy wormholes constrained by astrophysical observations

International Nuclear Information System (INIS)

Wang, Deng; Meng, Xin-he

2016-01-01

In this paper, we introduce the astrophysical observations into the wormhole research. We investigate the evolution behavior of the dark energy equation of state parameter ω by constraining the dark energy model, so that we can determine in which stage of the universe wormholes can exist by using the condition ω < -1. As a concrete instance, we study the Ricci dark energy (RDE) traversable wormholes constrained by astrophysical observations. Particularly, we find from Fig. 5 of this work, when the effective equation of state parameter ω X < -1 (or z < 0.109), i.e., the null energy condition (NEC) is violated clearly, the wormholes will exist (open). Subsequently, six specific solutions of statically and spherically symmetric traversable wormhole supported by the RDE fluids are obtained. Except for the case of a constant redshift function, where the solution is not only asymptotically flat but also traversable, the five remaining solutions are all non-asymptotically flat, therefore, the exotic matter from the RDE fluids is spatially distributed in the vicinity of the throat. Furthermore, we analyze the physical characteristics and properties of the RDE traversable wormholes. It is worth noting that, using the astrophysical observations, we obtain the constraints on the parameters of the RDE model, explore the types of exotic RDE fluids in different stages of the universe, limit the number of available models for wormhole research, reduce theoretically the number of the wormholes corresponding to different parameters for the RDE model, and provide a clearer picture for wormhole investigations from the new perspective of observational cosmology. (orig.)

Self-supervised Traversability Assessment in Field Environments with Lidar and Camera

DEFF Research Database (Denmark)

Hansen, Mikkel Kragh; Underwood, James; Karstoft, Henrik

, the visual classifier detects non-traversable image patches as outliers from a Gaussian Mixture Model that maintains the appearance of only traversable ground. Results Our method is evaluated using a diverse dataset of agricultural fields and orchards gathered with a perception research robot developed......Introduction The application of robotic automation within agriculture is increasing. There is a high demand for fully autonomous robots that are both efficient, reliable and affordable. In order to ensure safety, autonomous agricultural vehicles must perceive the environment and detect potential...... obstacles and threats across a variety of environmental conditions. In this paper, a self-supervised framework is proposed, combining laser range sensing from a lidar with images from a monocular camera to reliably assess terrain traversability/navigability. Methods The method uses a near-to-far approach...

CT-FC: more Comprehensive Traversal Focused Crawler

Directory of Open Access Journals (Sweden)

NFN Kuspriyanto

2012-03-01

Full Text Available In todays world, people depend more on the WWW information, including professionals who have to analyze the data according their domain to maintain and improve their business. A data analysis would require information that is comprehensive and relevant to their domain. Focused crawler as a topical based Web indexer agent is used to meet this applications information need. In order to increase the precision, focused crawler face the problem of low recall. The study on WWW hyperlink structure characteristics indicates that many Web documents are not strong connected but through co-citation & co-reference. Conventional focused crawler that uses forward crawling strategy could not visit the documents in these characteristics. This study proposes a more comprehensive traversal framework. As a proof, CT-FC (a focused crawler with the new traversal framework ran on DMOZ data that is representative to WWW characteristics. The results show that this strategy can increase the recall significantly.

Mammalian cell biology

International Nuclear Information System (INIS)

Elkind, M.M.

1975-01-01

Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

ON TRAVERSABILITY COST EVALUATION FROM PROPRIOCEPTIVE SENSING FOR A CRAWLING ROBOT

Directory of Open Access Journals (Sweden)

Jakub Mrva

2015-12-01

Full Text Available Traversability characteristics of the robot working environment are crucial in planning an efficient path for a robot operating in rough unstructured areas. In the literature, approaches to wheeled or tracked robots can be found, but a relatively little attention is given to walking multi-legged robots. Moreover, the existing approaches for terrain traversability assessment seem to be focused on gathering key features from a terrain model acquired from range data or camera image and only occasionally supplemented with proprioceptive sensing that expresses the interaction of the robot with the terrain. This paper addresses the problem of traversability cost evaluation based on proprioceptive sensing for a hexapod walking robot while optimizing different criteria. We present several methods of evaluating the robot-terrain interaction that can be used as a cost function for an assessment of the robot motion that can be utilized in high-level path-planning algorithms.

Self Sustained Traversable Wormholes Induced by Gravity’s Rainbow and Noncommutative Geometry

Directory of Open Access Journals (Sweden)

Garattini Remo

2013-09-01

Full Text Available We compare the effects of Noncommutative Geometry and Gravity’s Rainbow on traversable wormholes which are sustained by their own gravitational quantum fluctuations. Fixing the geometry on a well tested model, we find that the final result shows that the wormhole is of the Planckian size. This means that the traversability of the wormhole is in principle, but not in practice.

Traversability analysis for a mine safety inspection robot

CSIR Research Space (South Africa)

Senekal, F

2013-09-01

Full Text Available A new fast algorithm for traversability analysis of an arbitrary three-dimensional point cloud is presented. The algorithm segments a three-dimensional point cloud into vertical sections; each of which is clustered into bins and further analysed...

Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

Science.gov (United States)

Shin, Hae Jin; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Kim, Seok Hyun; Lee, Byung Seok; Kim, Ju Seok; Yun, Gee Young

2017-12-01

The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P squamous cell carcinoma treated with definitive CRT, the serum albumin level squamous cell carcinoma treated with definitive CRT is a significant prognostic factor. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Chemical determination of free radical-induced damage to DNA.

Science.gov (United States)

Dizdaroglu, M

1991-01-01

Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

Traversable braneworld wormholes supported by astrophysical observations

Science.gov (United States)

Wang, Deng; Meng, Xin-He

2018-02-01

In this study, we investigate the characteristics and properties of a traversable wormhole constrained by the current astrophysical observations in the framework of modified theories of gravity (MOG). As a concrete case, we study traversable wormhole space-time configurations in the Dvali-Gabadadze-Porrati (DGP) braneworld scenario, which are supported by the effects of the gravity leakage of extra dimensions. We find that the wormhole space-time structure will open in terms of the 2 σ confidence level when we utilize the joint constraints supernovae (SNe) Ia + observational Hubble parameter data (OHD) + Planck + gravitational wave (GW) and z based on various energy conditions; (ii) we can offer a strict restriction to the local wormhole space-time structure by using the current astrophysical observations; and (iii) we can clearly identify a physical gravitational resource for the wormholes supported by astrophysical observations, namely the dark energy components of the universe or equivalent space-time curvature effects from MOG. Moreover, we find that the strong energy condition is always violated at low redshifts.

EAST93: Geophysical traverse from the Transantarctic Mountains to the Wilkes Basin, East Antarctica

Science.gov (United States)

ten Brink, Uri S.; Bannister, Stephen

1995-01-01

The East Antarctic Seismic Traverse (EAST93) was a geophysical traverse designed to image the bedrock under the East Antarctic ice cap. The traverse started 10 km west of the Taylor Dome drill site and 25 km west of the exposed bedrock of the Transantarctic Mountains at Lashly Mt. and ended 323 km west of the drill site over the Wilkes subglacial basin (Fig. 1). The traverse was located subparallel to latitude 78° S starting 30-50 km north of the Victoria Land Traverse (1958-1959). It was carried out jointly by the U.S. Geological Survey and Stanford University, U.S.A., together with the Institute of Geological and Nuclear Sciences, and Victoria University, New Zealand, during December 1993 and January 1994. The geophysical traverse included 236 km of multichannel seismic reflection data at 150 m shot intervals, 312.5 km of gravity data collected at intervals of 2.1 km, 312.5 km of magnetic data (total field intensity) collected at average intervals of 0.5 km, and 205 km of ground penetrating radar at intervals of 77 m. Relative locations and elevations of the entire traverse were measured at intervals of 150 m by traditional surveying methods, and tied to three absolute locations measured by the Global Positioning System (GPS). EAST93 is the first large-scale geophysical traverse on the polar plateau to our knowledge since the early 1960s. As such, the experiment presented several logistical challenges: (1) how to collect regional seismic profiles during the short Antarctic summer; (2) how to keep the scientific instruments running with minimal protection in harsh conditions; and (3) how to combine daily moves of camp with full days of work. The scientific and logistical aspects of the project proceeded, in general, according to plan despite the harsh conditions and our lack of previous experience on the polar plateau. Two unanticipated problems affected the progress of the work: the strong wind which slowed seismic acquisition, and the break-down of one of the

Vertical and lateral forces when a permanent magnet above a superconductor traverses in arbitrary directions

Science.gov (United States)

Yang, Yong

2008-12-01

In an actual levitation system composed of high temperature superconductors (HTSs) and permanent magnets (PMs), the levitating bodies may traverse in arbitrary directions. Many previous researchers assumed that the levitating bodies moved in a vertical direction or a lateral direction in order to simplify the problem. In this paper, the vertical and lateral forces acting on the PM are calculated by the modified frozen-image method when a PM above an HTS traverses in arbitrary directions. In order to study the effects of the movement directions on the vertical and lateral forces, comparisons of the forces that act on a PM traversing in a tilted direction with those that act on a PM traversing in a vertical direction or a lateral direction have been presented.

Vertical and lateral forces when a permanent magnet above a superconductor traverses in arbitrary directions

Energy Technology Data Exchange (ETDEWEB)

Yang Yong [Key Laboratory of Applied Superconductivity, Chinese Academy of Sciences, Beijing 100190 (China); Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China)], E-mail: yy@mail.iee.ac.cn

2008-12-15

In an actual levitation system composed of high temperature superconductors (HTSs) and permanent magnets (PMs), the levitating bodies may traverse in arbitrary directions. Many previous researchers assumed that the levitating bodies moved in a vertical direction or a lateral direction in order to simplify the problem. In this paper, the vertical and lateral forces acting on the PM are calculated by the modified frozen-image method when a PM above an HTS traverses in arbitrary directions. In order to study the effects of the movement directions on the vertical and lateral forces, comparisons of the forces that act on a PM traversing in a tilted direction with those that act on a PM traversing in a vertical direction or a lateral direction have been presented.

Vertical and lateral forces when a permanent magnet above a superconductor traverses in arbitrary directions

International Nuclear Information System (INIS)

Yang Yong

2008-01-01

In an actual levitation system composed of high temperature superconductors (HTSs) and permanent magnets (PMs), the levitating bodies may traverse in arbitrary directions. Many previous researchers assumed that the levitating bodies moved in a vertical direction or a lateral direction in order to simplify the problem. In this paper, the vertical and lateral forces acting on the PM are calculated by the modified frozen-image method when a PM above an HTS traverses in arbitrary directions. In order to study the effects of the movement directions on the vertical and lateral forces, comparisons of the forces that act on a PM traversing in a tilted direction with those that act on a PM traversing in a vertical direction or a lateral direction have been presented.

Absorbed dose from traversing spherically symmetric, Gaussian radioactive clouds

International Nuclear Information System (INIS)

Thompson, J.M.; Poston, J.W.

1999-01-01

If a large radioactive cloud is produced, sampling may require that an airplane traverse the cloud. A method to predict the absorbed dose to the aircrew from penetrating the radioactive cloud is needed. Dose rates throughout spherically symmetric Gaussian clouds of various sizes, and the absorbed doses from traversing the clouds, were calculated. Cloud size is a dominant parameter causing dose to vary by orders of magnitude for a given dose rate measured at some distance. A method to determine cloud size, based on dose rate readings at two or more distances from the cloud center, was developed. This method, however, failed to resolve the smallest cloud sizes from measurements made at 1,000 m to 2,000 m from the cloud center

Repair processes for photochemical damage in mammalian cells

International Nuclear Information System (INIS)

Cleaver, J.E.

1974-01-01

Repair processes for photochemical damage in cells following uv irradiation are reviewed. Cultured fibroblast cells from human patients with xeroderma pigmentosum were used as an example to illustrate aspects of repair of injuries to DNA and proteins. (250 references) (U.S.)

Rapid Separation of Disconnected Triangle Meshes Based on Graph Traversal

International Nuclear Information System (INIS)

Ji, S J; Wang, Y

2006-01-01

In recent year, The STL file become a de facto standard on the file presentation in CAD/CAM, computer graph and reverse engineering. When point cloud which is obtained by scanning object body using optical instrument is used to reconstruct an original model, the points cloud is presented by the STL file. Usually, datum of several separated and relative objects are stored in a single STL file, when such a file is operated by a computer, the datum in the file is firstly separated and then each element of every triangle pitch on the triangle mesh is traversed and visited and is calculated. The problem is analyzed and studied by many experts, but there is still a lack of a simple and quick algorithm. An algorithm which uses graph traversal to traverse each element of the triangle meshes and separate several disconnected triangle meshes is presented by the paper, the searching and calculating speed of the data on the triangle meshes is enhanced, memory size of the computer is reduced, complexity of the data structure is simplified and powerful guarantee is made for the next process by using this algorithm

Oxidative damage and aging: spotlight on mitochondria.

Science.gov (United States)

Linford, Nancy J; Schriner, Samuel E; Rabinovitch, Peter S

2006-03-01

Whereas free radical damage has been proposed as a key component in the tissue degeneration associated with aging, there has been little evidence that free radical damage limits life span in mammals. The current research shows that overexpression of the antioxidant enzyme catalase in mitochondria can extend mouse life span. These results highlight the importance of mitochondrial damage in aging and suggest that when targeted appropriately, boosting antioxidant defenses can increase mammalian life span.

Quantitative aspects of repair of potentially lethal damage in mammalian cells

International Nuclear Information System (INIS)

Iliakis, G.; Pohlit, W.

1979-01-01

Stationary cultures of Ehrlich ascites tumour cells were irradiated with X-rays and then immediately or after a time interval tsub(rep) plated to measure the survival. The increase in survival observed after delayed plating was interpreted as repair of potentially lethal damage. A cybernetic model was used to analyse these data. Three states of damage were assumed for the cells. In state A the cells could grow to macrocolonies, in state B the cells suffered potentially lethal damage and could grow to macrocolonies only if they were allowed to repair the damage and in state C the cells were lethally damaged. A method of deriving the values of the parameters of the model from the experimental data was given. The dependence of the reaction rate constant of the repair potentially lethal damage on the dose D was used to derive a possible mechanism for the production of the shoulder in the dose effect curve. Finally this model was compared with other models of radiation action in living cells. (author)

Asymmetric segregation of damaged cellular components in spatially structured multicellular organisms.

Directory of Open Access Journals (Sweden)

Charlotte Strandkvist

Full Text Available The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

78 FR 25407 - Safety Zones; National Cherry Festival Air Show and Fireworks Display; West Grand Traverse Bay...

Science.gov (United States)

2013-05-01

...-AA00 Safety Zones; National Cherry Festival Air Show and Fireworks Display; West Grand Traverse Bay... National Cherry Festival in Traverse City, MI will host an air show over the West Arm of Grand Traverse Bay. At the conclusion of the National Cherry Festival on July 6, 2013, fireworks will be launched in...

Some important advances in DNA repair study on the mammalian cells

International Nuclear Information System (INIS)

Xia Shouxuan.

1991-01-01

In the recent years the study of DNA damage and repair in the mammalian cells has gone deeply at gene level and got the following advances: (1) For a long time DNA has been considered to be an uniform unit in case of damage and repair. Now this concept should be replaced by the non-random distribution of damage and heterogenous repair in the genome. These would allow us to study cellular mutagenesis, carcinogenesis, aging and dying processes in great detail, and would be beneficial to the elucidation of mechanisms of radiation sickness and chemical toxicology. (2) The advent of new techniques in molecular biology has made it possible to isolate and clone the human DNA repair genes. Up to now more than ten human DNA repair genes have been cloned and these works would have an important impact on the theoretical and practical study in this field. Because DNA repair system is very complicate, voluminous work should be done in the future. (3) The technique of gene transfer has been efficiently used in the study of DNA repair in mammalian cells and has made great contribution in the cellular engineering. It could modify the genetic behavior of the gene-accepting cells, and enhance the DNA repair ability to physical and chemical damages. Human gene therapy for DNA deficient diseases is now on the day

[Mathematical modeling of synergistic interaction of sequential thermoradiation action on mammalian cells].

Science.gov (United States)

Belkina, S V; Semkina, M A; Kritskiĭ, R O; Petin, V G

2010-01-01

Data obtained by other authors for mammalian cells treated by sequential action of ionizing radiation and hyperthermia were used to estimate the dependence of synergistic enhancement ratio on the ratio of damages induced by these agents. Experimental results were described and interpreted by means of the mathematical model of synergism in accordance with which the synergism is expected to result from the additional lethal damage arising from the interaction of sublesions induced by both agents.

Radiation effects in mammalian cells in vitro

International Nuclear Information System (INIS)

Hill, C.K.; Han, A.; Elkind, M.M.; Wells, R.L.; Buess, E.M.; Lin, C.M.

1985-01-01

The purpose of this research effort is to elucidate the mechanisms for the radiation-induced changes in mammalian cells that lead to cell death, mutation, neoplastic transformation, DNA damage, and chromosomal alterations. Of particular interest are the effects of low-dose-rate and fractionated irradiation on these end points with respect to the mechanisms whereby these effects are influenced by cellular repair processes, inhibitors, and promoters that act at the genetic or biochemical level. 17 refs

GPU accelerated tandem traversal of blocked bounding volume hierarchy collision detection for multibody dynamics

DEFF Research Database (Denmark)

Damkjær, Jesper; Erleben, Kenny

2009-01-01

and a simultaneous descend in the tandem traversal. The data structure design and traversal are highly specialized for exploiting the parallel threads in the NVIDIA GPUs. As proof-of-concept we demonstrate a GPU implementation for a multibody dynamics simulation, showing an approximate speedup factor of up to 8...

Heritable non-lethal damage to cultured human cells irradiated with heavy ions

International Nuclear Information System (INIS)

Walker, J.T.; Walker, O.A.

2002-01-01

During interplanetary flights the nuclei of all of a crew member's cells could be traversed by at least one high-LET (linear energy transfer) cosmic-ray particle. In mammalian cells irradiated in vitro about 1 in 10,000 of the surviving cells traversed by heavy particles is transformed to malignancy or mutated. What, if anything, happens to the remaining >99% of surviving cells? A retrospective analysis of archived data and samples from heavy-ion irradiation experiments with cultured human cells in vitro indicated that heavy ions caused a dose- and LET-dependent reduction in growth rates of progeny of irradiated cells, based on colony-size distributions. The maximum action cross section for this effect is between 100 and 300 μm 2 , at least as large as the cell nuclear area and up to 3 times the cross section for cell killing. Thus, heritable slow growth is the most prevalent effect of high-LET radiations on cultured animal cells, which may have implications for crew health during deep space travel. (author)

Metformin (dimethyl-biguanide induced DNA damage in mammalian cells

Directory of Open Access Journals (Sweden)

Rubem R. Amador

2012-01-01

Full Text Available Metformin (dimethyl-biguanide is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays and in mice (micronucleus assays. Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

Pose estimation-based path planning for a tracked mobile robot traversing uneven terrains

OpenAIRE

Jun , Jae-Yun; Saut , Jean-Philippe; Benamar , Faïz

2015-01-01

International audience; A novel path-planning algorithm is proposed for a tracked mobile robot to traverse uneven terrains, which can efficiently search for stability sub-optimal paths. This algorithm consists of combining two RRT-like algorithms (the Transition-based RRT (T-RRT) and the Dynamic-Domain RRT (DD-RRT) algorithms) bidirectionally and of representing the robot-terrain interaction with the robot’s quasi-static tip-over stability measure (assuming that the robot traverses uneven ter...

Meta-Analysis of Attitudes toward Damage-Causing Mammalian Wildlife

Science.gov (United States)

KANSKY, RUTH; KIDD, MARTIN; KNIGHT, ANDREW T

2014-01-01

Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. Meta-Análisis de las Posturas hacia la Mam

Tunneling and traversal of ultracold three-level atoms through vacuum-induced potentials

Energy Technology Data Exchange (ETDEWEB)

Badshah, Fazal; Irfan, Muhammad; Qamar, Shahid [Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences, Nilore, Islamabad 45650 (Pakistan); Qamar, Sajid [Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan)

2011-09-15

The passage of ultracold three-level atoms through the potential induced by the vacuum cavity mode is discussed using cascade atomic configuration. We study the tunneling or traversal time of the ultracold atoms via a bimodal high-Q cavity. It is found that the phase time, which may be considered as a measure for the time required to traverse the cavity, exhibits superclassical and subclassical behaviors. Further, the dark states and interference effects in cascade atomic configuration may influence the passage time of the atom through the cavity.

Tunneling and traversal of ultracold three-level atoms through vacuum-induced potentials

International Nuclear Information System (INIS)

Badshah, Fazal; Irfan, Muhammad; Qamar, Shahid; Qamar, Sajid

2011-01-01

The passage of ultracold three-level atoms through the potential induced by the vacuum cavity mode is discussed using cascade atomic configuration. We study the tunneling or traversal time of the ultracold atoms via a bimodal high-Q cavity. It is found that the phase time, which may be considered as a measure for the time required to traverse the cavity, exhibits superclassical and subclassical behaviors. Further, the dark states and interference effects in cascade atomic configuration may influence the passage time of the atom through the cavity.

Dihydropyridines decrease X-ray-induced DNA base damage in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Wojewodzka, M., E-mail: marylaw@ichtj.waw.pl [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Gradzka, I.; Buraczewska, I.; Brzoska, K.; Sochanowicz, B. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Goncharova, R.; Kuzhir, T. [Institute of Genetics and Cytology, Belarussian National Academy of Sciences, Minsk (Belarus); Szumiel, I. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland)

2009-12-01

Compounds with the structural motif of 1,4-dihydropyridine display a broad spectrum of biological activities, often defined as bioprotective. Among them are L-type calcium channel blockers, however, also derivatives which do not block calcium channels exert various effects at the cellular and organismal levels. We examined the effect of sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate (denoted here as DHP and previously also as AV-153) on X-ray-induced DNA damage and mutation frequency at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in Chinese hamster ovary CHO-K1 cells. Using formamido-pyrimidine glycosylase (FPG) comet assay, we found that 1-h DHP (10 nM) treatment before X-irradiation considerably reduced the initial level of FPG-recognized DNA base damage, which was consistent with decreased 8-oxo-7,8-dihydro-2'-deoxyguanosine content and mutation frequency lowered by about 40%. No effect on single strand break rejoining or on cell survival was observed. Similar base damage-protective effect was observed for two calcium channel blockers: nifedipine (structurally similar to DHP) or verapamil (structurally unrelated). So far, the specificity of the DHP-caused reduction in DNA damage - practically limited to base damage - has no satisfactory explanation.

Action spectra in mammalian cells exposed to ultraviolet radiation

International Nuclear Information System (INIS)

Anon.

1981-01-01

A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

Formation and repair of gamma-ray induced nucleic acid base damage in bacteria and mammalian cells. Final report, September 1, 1973--August 31, 1976

International Nuclear Information System (INIS)

Cerutti, P.A.

1976-01-01

Results are summarized from a three-year study of the formation and repair of γ-ray induced thymine damage in bacteria and mammalian cells. A systematic study was made of the formation of a specific type of ionizing radiation induced base damage under in vivo conditions. Assay for the determination of γ-ray products of the 5,6-dihydroxy-dihydrothymine type (alkaline-acid degradation assay) and a method for the determination of the formation of 5-methylene-uracil radicals (formation of ( 3 H)H 2 O from thymine-methyl ( 3 H)) are discussed. The radiation-chemical reactivity of thymine decreased according to the following pattern in different biological systems: phi X174-DNA greater than E. coli DNA = phi X174 phage much greater than HeLa chromatin greater than E. coli cells greater than human fibroblasts WI-38. In WI-38 the efficiency of formation of 5-methylene-uracil radicals was 1.6 x 10 -3 per Krad and 10 6 daltons DNA and of products of the 5,6-dihydroxy-dihydrothymine type 0.54 x 10 -3 per Krad per 10 6 daltons DNA (uncorrected). It was concluded that γ-rays produce DNA single strand breaks and (total) base damage with comparable efficiencies under in vivo conditions in cultured cells. A list is included of 18 published papers that report the findings in detail

An Experimental Investigation of an Airfoil Traversing Across a Shear Flow

Science.gov (United States)

Hamedani, Borhan A.; Naguib, Ahmed; Koochesfahani, Manoochehr

2017-11-01

While the aerodynamics of an airfoil in a uniform approach flow is well understood, less attention has been paid to airfoils in non-uniform flows. An aircraft encounters such flow, for example, during landing through the air wake of an aircraft carrier. The present work is focused on investigating the fundamental aerodynamics of airfoils in such an environment using canonical flow experiments. To generate a shear approach flow, a shaped honeycomb block is employed in a wind tunnel setup. Direct force measurements are performed on a NACA 0012 airfoil, with an aspect ratio of 1.8, as the airfoil traverses steadily across the shear region. Measurements are conducted at a chord Reynolds number Rec 75k, based on the mean approach stream velocity at the center of the shear zone, for a range of airfoil traverse velocities and angles of attack (0 - 12 degree). The results are compared to those obtained for the same airfoil when placed statically at different points along the traverse path inside the shear zone. The comparison enables examination of the applicability of quasi-steady analysis in computing the forces on the moving airfoil. This work is supported by ONR Grant Number N00014-16-1-2760.

Traversing incore probe device

International Nuclear Information System (INIS)

Yoshioka, Michiko.

1985-01-01

Purpose: To measure the neutron flux distribution in the reactor core always at a high accuracy. Constitution: A nuclear fission ionizing chamber type detector is disposed at the end of a cable for sending a detection signal of a traversing incore probe device and, further, a gamma-ray ionizing chamber type detector is connected in adjacent therewith and a selection circuit for selecting both of the detection signals and inputting them to a display device is disposed. Then, compensation for the neutron monitors is conducted by the gamma-ray ionizing chamber type detector during normal operation in which control rods are not driven and the positioning is carried out by the nuclear fission ionizing chamber type detector. Furthermore, both of the compensation for the neutron detector and the positioning are carried out by the nuclear fission ionizing chamber type detector upon starting where the control rods are driven. (Sekiya, K.)

System and Method for Traversing Pipes

Science.gov (United States)

Graf, Jodi (Inventor); Pettinger, Ross (Inventor); Azimi, Shaun (Inventor); Magruder, Darby (Inventor); Ridley, Justin (Inventor); Lapp, Anthony (Inventor)

2017-01-01

A system and method is provided for traversing inside one or more pipes. In an embodiment, a fluid is injected into the one or more pipes thereby promoting a fluid flow. An inspection device is deployed into the one or more pipes at least partially filled with a flowing fluid. The inspection device comprises a housing wherein the housing is designed to exploit the hydrokinetic effects associated with a fluid flow in one or more pipes as well as maneuver past a variety of pipe configurations. The inspection device may contain one or more sensors capable of performing a variety of inspection tasks.

Peano—A Traversal and Storage Scheme for Octree-Like Adaptive Cartesian Multiscale Grids

KAUST Repository

Weinzierl, Tobias

2011-01-01

Almost all approaches to solving partial differential equations (PDEs) are based upon a spatial discretization of the computational domain-a grid. This paper presents an algorithm to generate, store, and traverse a hierarchy of d-dimensional Cartesian grids represented by a (k = 3)- spacetree, a generalization of the well-known octree concept, and it also shows the correctness of the approach. These grids may change their adaptive structure throughout the traversal. The algorithm uses 2d + 4 stacks as data structures for both cells and vertices, and the storage requirements for the pure grid reduce to one bit per vertex for both the complete grid connectivity structure and the multilevel grid relations. Since the traversal algorithm uses only stacks, the algorithm\\'s cache hit rate is continually higher than 99.9 percent, and the runtime per vertex remains almost constant; i.e., it does not depend on the overall number of vertices or the adaptivity pattern. We use the algorithmic approach as the fundamental concept for a mesh management for d-dimensional PDEs and for a matrix-free PDE solver represented by a compact discrete 3 d-point operator. In the latter case, one can implement a Jacobi smoother, a Krylov solver, or a geometric multigrid scheme within the presented traversal scheme which inherits the low memory requirements and the good memory access characteristics directly. © 2011 Society for Industrial and Applied Mathematics.

Lunar Surface Potential Increases during Terrestrial Bow Shock Traversals

Science.gov (United States)

Collier, Michael R.; Stubbs, Timothy J.; Hills, H. Kent; Halekas, Jasper; Farrell, William M.; Delory, Greg T.; Espley, Jared; Freeman, John W.; Vondrak, Richard R.; Kasper, Justin

2009-01-01

Since the Apollo era the electric potential of the Moon has been a subject of interest and debate. Deployed by three Apollo missions, Apollo 12, Apollo 14 and Apollo 15, the Suprathermal Ion Detector Experiment (SIDE) determined the sunlit lunar surface potential to be about +10 Volts using the energy spectra of lunar ionospheric thermal ions accelerated toward the Moon. We present an analysis of Apollo 14 SIDE "resonance" events that indicate the lunar surface potential increases when the Moon traverses the dawn bow shock. By analyzing Wind spacecraft crossings of the terrestrial bow shock at approximately this location and employing current balancing models of the lunar surface, we suggest causes for the increasing potential. Determining the origin of this phenomenon will improve our ability to predict the lunar surface potential in support of human exploration as well as provide models for the behavior of other airless bodies when they traverse similar features such as interplanetary shocks, both of which are goals of the NASA Lunar Science Institute's Dynamic Response of the Environment At the Moon (DREAM) team.

Bearing Capacity of Floating Ice Sheets under Short-Term Loads: Over-Sea-Ice Traverse from McMurdo Station to Marble Point

Science.gov (United States)

2015-01-01

under Short-Term Loads Over-Sea-Ice Traverse from McMurdo Station to Marble Point Co ld R eg io ns R es ea rc h an d En gi ne er in g La bo ra...Traverse from McMurdo Station to Marble Point Jason C. Weale and Devinder S. Sodhi Cold Regions Research and Engineering Laboratory (CRREL) U.S...Division of Polar Programs operates an over-sea-ice traverse from McMurdo Station to rou- tinely resupply Marble Point Camp. The traverse requires that

Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

International Nuclear Information System (INIS)

Lopez-Larraza, Daniel M.; Padron, Juan; Ronci, Natalia E.; Vidal Rioja, Lidia A.

2006-01-01

Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 o C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

Energy Technology Data Exchange (ETDEWEB)

Lopez-Larraza, Daniel M. [IMBICE, C.C. 403, 1900 La Plata (Argentina)]. E-mail: danielop@imbice.org.ar; Padron, Juan [IMBICE, C.C. 403, 1900 La Plata (Argentina); Ronci, Natalia E. [IMBICE, C.C. 403, 1900 La Plata (Argentina); Vidal Rioja, Lidia A. [IMBICE, C.C. 403, 1900 La Plata (Argentina)

2006-08-30

Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 {sup o}C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells.

Traversal-time distribution for a classical time-modulated barrier

International Nuclear Information System (INIS)

Mateos, J.L.

1999-01-01

The classical problem of a time-modulated barrier, inspired by the Buettiker and Landauer model to study the tunneling times, is analyzed. We show that the traversal-time distribution of an ensemble of non-interacting particles that arrives at the oscillating barrier, obeys a distribution with a power-law tail. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Neutron irradiation of bacteria in the presence and absence of secondary charged-particle equilibrium

International Nuclear Information System (INIS)

Lunec, J.; Cramp, W.A.; Hornsey, S.

1980-01-01

The survival rate of Shigella flexneri has been measured for irradiation with 7-MeV neutrons in the presence and absence of secondary charged-particle equilibrium. The data were analyzed to assess the separate response of the cells to the knock-on proton and α-particle plus heavy-recoil components. A detailed consideration of the frequency of α-particle and heavy-recoil traversals of the cell has been made to explain our results, and in addition we have applied this approach to analyze the earlier results obtained with mammalian cells. We conclude that of the secondary charged-particles produced by the Hammersmith neutron beam, the highest LET particles, the heavy-recoil nuclei, contribute a minor proportion of damage to bacteria but form a major contribution of damage in mammalian cells. The reduction in oxygen enhancement ratio (OER) with neutrons compared with low LET radiation for mammalian cells is due almost entirely to the influence of the heavy recoils and the contribution of the α-particle and knock-on protons to the reduction of the OER is relatively minor. For Shigella flexneri the α particles and heavy recoils make approximately equal contributions to the reduction in OER

Regeneration of hair cells in the mammalian vestibular system.

Science.gov (United States)

Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

2016-06-01

Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

Repair of radiation damage in mammalian cells: its relevance to environmental effects

International Nuclear Information System (INIS)

Han, A.; Elkind, M.M.

1979-01-01

Assessment of the potential biological hazards associated with energy production technologies involves the quantitation of risk on the basis of dose-effect dependencies, from which, it is hoped, some safety guidelines can be developed. Our current knowledge of the biological importance of damage/repair processes stems by and large from radiation studies which clearly demonstrate that cellular response to radiation depends upon the ability of cells to repair the damage. Apparently, the same is true for cellular response to different chemical agents. Drawing upon our experiences from radiation studies, we demonstrate the relevance of ongoing repair processes, as evident in the studies of radiation induced cell killing and neoplastic transformation, to the type of risk estimates that might be associated with the hazards from energy production technologies. The effect of repair on cell survival is considered. It is evident from our studies that in the region of small doses, repair of damage relative to cell lethality is of importance in estimating the magnitude of effect. Aside from the cytotoxic effects in terms of cell killing, one of the greatest concerns associated with energy production is the potential of a given technology, or its effluents, to produce cancer. It is therefore of importance to quantify the risk in this context of damage registration and possible effect of repair on damage expression. It has been generally established that exposure of normal cells in culture to a variety of known carcinogens results in neoplastic transformation. Our observations with C3H/10T1/2 cells in culture lend direct evidence for the hypothesis that reduced tumor incidences at low dose rates of radiation could be due to the repair of induced damage

Mutation in cultured mammalian cells

International Nuclear Information System (INIS)

Nakamura, N.; Okada, S.

1982-01-01

Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

Intracranial neurenteric cyst traversing the brainstem

Directory of Open Access Journals (Sweden)

Jasmit Singh

2015-01-01

Full Text Available Neurenteric cysts (NECs, also called enterogenous cysts, are rare benign endodermal lesions of the central nervous system that probably result from separation failure of the notochord and upper gastrointestinal tract. Most frequently they are found in the lower cervical spine or the upper thoracic spine. Intracranial occurrence is rare and mostly confined to infratentorial compartment, in prepontine region [51%]. Other common locations are fourth ventricle and cerebellopontine angle. There are few reports of NEC in medulla or the cerebellum. Because of the rarity of the disease and common radiological findings, they are misinterpreted as arachnoid or simple cysts until the histopathological confirmation, unless suspected preoperatively. We herein report a rare yet interesting case of intracranial NEC traversing across the brainstem.

ArcGIS Digitization of Apollo Surface Traverses

Science.gov (United States)

Petro, N. E.; Bleacher, J. E.; Gladdis, L. R.; Garry, W. B.; Lam, F.; Mest, S. C.

2012-01-01

The Apollo surface activities were documented in extraordinary detail, with every action performed by the astronauts while on the surface recorded either in photo, audio, film, or by written testimony [1]. The samples and in situ measurements the astronauts collected while on the lunar surface have shaped our understanding of the geologic history of the Moon, and the earliest history and evolution of the inner Solar System. As part of an ongoing LASERfunded effort, we are digitizing and georeferencing data from astronaut traverses and spatially associating them to available, co-registered remote sensing data. Here we introduce the products produced so far for Apollo 15, 16, and 17 missions.

Role of Rad54, Rad54b and Snm1 in DNA damage repair

NARCIS (Netherlands)

J. Wesoly (Joanna)

2003-01-01

textabstractThe aim of this thesis is to investigate the function of a number of genes involved in mammalian DNA damage repair, in particular in repair of DNA double-strand breaks (DSBs). Among a large number of different damages that can be introduced to DNA, DSBs are especially toxic. If

Time-Lapse Monitoring of DNA Damage Colocalized With Particle Tracks in Single Living Cells

Energy Technology Data Exchange (ETDEWEB)

McFadden, Conor H. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hallacy, Timothy M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Physics and Astronomy, Rice University, Houston, Texas (United States); Flint, David B. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Granville, Dal A. [Department of Medical Physics, The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada); Asaithamby, Aroumougame [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, Texas (United States); Sahoo, Narayan [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akselrod, Mark S. [Crystal Growth Division, Landauer, Inc, Stillwater, Oklahoma (United States); Sawakuchi, Gabriel O., E-mail: gsawakuchi@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States)

2016-09-01

Purpose: Understanding the DNA damage and repair induced by hadron therapy (HT) beams is crucial for developing novel strategies to maximize the use of HT beams to treat cancer patients. However, spatiotemporal studies of DNA damage and repair for beam energies relevant to HT have been challenging. We report a technique that enables spatiotemporal measurement of radiation-induced damage in live cells and colocalization of this damage with charged particle tracks over a broad range of clinically relevant beam energies. The technique uses novel fluorescence nuclear track detectors with fluorescence confocal laser scanning microscopy in the beam line to visualize particle track traversals within the subcellular compartments of live cells within seconds after injury. Methods and Materials: We designed and built a portable fluorescence confocal laser scanning microscope for use in the beam path, coated fluorescence nuclear track detectors with fluorescent-tagged live cells (HT1080 expressing enhanced green fluorescent protein tagged to XRCC1, a single-strand break repair protein), placed the entire assembly into a proton therapy beam line, and irradiated the cells with a fluence of ∼1 × 10{sup 6} protons/cm{sup 2}. Results: We successfully obtained confocal images of proton tracks and foci of DNA single-strand breaks immediately after irradiation. Conclusions: This technique represents an innovative method for analyzing biological responses in any HT beam line at energies and dose rates relevant to therapy. It allows precise determination of the number of tracks traversing a subcellular compartment and monitoring the cellular damage therein, and has the potential to measure the linear energy transfer of each track from therapeutic beams.

Scattering of electromagnetic waves by a traversable wormhole

Directory of Open Access Journals (Sweden)

B. Nasr Esfahani

2005-09-01

Full Text Available   Replacing the wormhole geometry with an equivalent medium using the perturbation theory of scattering and the Born approximation, we have calculated the differential scattering cross section of electromagnetic waves by a traversable wormhole. It is shown that scattering at long wavelenghts can essentially distinguish wormhole from ordinary scattering object. Some of the zeros of the scattering cross section are determined which can be used for estimating the radius of the throat of wormholes. The known result that in this kind of scattering the linear polarization remains unchanged is verified here.

Repair of radiation damage caused by cyclotron-produced neutrons

International Nuclear Information System (INIS)

Martins, B.I.

1979-01-01

Hall et al. present experimental data on repair of sublethal damage in cultured mammalian cells exposed to 35 MeV neutrons and 60 Co γ rays. Hall and Kraljevic present experimental data on repair of potentially lethal damage in cultured mammalian cells exposed to 35 MeV neutrons and 210 kVp x rays. These results of Hall et al. are very difficult to explain from basic concepts in radiobiology. Contrary to Rossi, these data do not support his thesis that repair of radiation damage is dose-dependent and linear energy transfer independent. Nor do these results meet the expectations of multitarget-single hit theory which would require dose-independent repair equal to n. The observation of the same extrapolation number for neutrons and for x rays is also surprising. From the point of view of radiotherapy, the doses of interest are about 140 rad for neutrons and about 300 rad for x rays. There are no data for repair of potentially lethal damage below 800 rad for x rays and 400 rad for neutrons. The difference in survival between single and split dose is negligible up to a total of about 600 rad of x rays or of neutrons. These data of Hall et al. therefore have little significance to radiotherapists and are an enigma to radiobiologists

Combined effects of hyperthermia and radiation in cultured mammalian cells

International Nuclear Information System (INIS)

Ben-Hur, E.; Elkind, M.M.; Riklis, E.

1977-01-01

Hyperthermia (temperatures of 39 0 C or higher) enhances the killing of mammalian cells by ionizing radiation (fission-spectrum neutrons and x-rays). The nature and the magnitude of the enhanced radiation killing varies with temperature and for a fixed temperature during irradiation, the enhanced lethality varies inversely with dose rate. For temperatures up to 41 0 C, dose fractionation measurements indicate that hyperthermia inhibits the repair of sublethal damage. At higher temperatures, the expression of potentially lethal damage is enhanced. Since the effect of heat is greatest in cells irradiated during DNA synthesis, the radiation age-response pattern is flattened by hyperthermia. In addition to the enhanced cell killing described above, three other features of the effect of hyperthermia are important in connection with the radiation treatment of cancer. The first is that heat selectively sensitizes S-phase cells to radiation. The second is that it takes radiation survivors 10 to 20 hrs after a modest heat treatment to recover their ability to repair sublethal damage. And the third is that hyperthermia reduces the magnitude of the oxygen enhancement ratio. Thus, heat if applied selectively, could significantly increase the margin of damage between tumors and normal tissues

Repair of traumatized mammalian hair cells via sea anemone repair proteins.

Science.gov (United States)

Tang, Pei-Ciao; Smith, Karen Müller; Watson, Glen M

2016-08-01

Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea. © 2016. Published by The Company of Biologists Ltd.

X-rays sensitive mammalian cell mutant

International Nuclear Information System (INIS)

Utsumi, Hiroshi

1982-01-01

A phenomenon that in x-ray-sensitive mammalian-cell mutants, cellular death due to x-ray radiation was not increased by caffeine, but on the contrary, the dead cells were resuscitated by it was discussed. The survival rate of mutant cells increased by caffein in a low concentration. This suggested that caffeine may have induced some mechanism to produce x-ray resistant mutant cells. Postirradiation treatment with caffeine increased considerably the survival rate of the mutant cells, and this suggested the existence of latent caffeine-sensitive potentially lethal damage repair system. This system, after a few hours, is thought to be substituted by caffeine-resistant repair system which is induced by caffeine, and this may be further substituted by x-ray-resistant repair system. The repair system was also induced by adenine. (Ueda, J.)

Transmission coefficient, resonant tunneling lifetime and traversal time in multibarrier semiconductor heterostructure

Energy Technology Data Exchange (ETDEWEB)

Nanda, Jyotirmayee [Department of Physics, National Institute of Technology, Rourkela, 769008 (India)]. E-mail: jnanda_b9@rediffmail.com; Mahapatra, P.K. [Department of Physics and Technophysics, Vidyasagar University, Midnapore, 721102 (India)]. E-mail: pkmahapatra@vidyasagar.ac.in; Roy, C.L. [Department of Physics and Meterology, Indian Institute of Technology, Kharagpur, 721302 (India)

2006-09-01

A computational model based on non-relativistic approach is proposed for the determination of transmission coefficient, resonant tunneling energies, group velocity, resonant tunneling lifetime and traversal time in multibarrier systems (GaAs/Al {sub y} Ga{sub 1-} {sub y} As) for the entire energy range {epsilon}V {sub 0}, V {sub 0}, being the potential barrier height. The resonant energy states were found to group into allowed tunneling bands separated by forbidden gaps. The tunneling lifetime and the traversal time are found to have minimum values at the middle of each allowed band. Further, It is observed that the electrons with energies in the higher tunneling band could tunnel out faster than those with energies in the lower band. Moreover, an additional resonant peak in resonant energy spectrum indicated the presence of a surface state where resonant tunneling occurs.

Traversing the interior landscape: five dialogues in existential space

OpenAIRE

Roes, Remco

2016-01-01

“Traversing the interior landscape: five dialogues in existential space” examines how existing spaces can be used as a basis for their rearrangement into meaningful, exitential (‘wezenlijke’) places. The research consists of a textual part and an artistic part (a series of works and exhibitions, including a retrospective on show in CIAP (Hasselt) from december 2015 – march 2016). One of the innovative aspects of this research is the unique methodology that was used. Through the point of vi...

Phosphorylation of human INO80 is involved in DNA damage tolerance

International Nuclear Information System (INIS)

Kato, Dai; Waki, Mayumi; Umezawa, Masaki; Aoki, Yuka; Utsugi, Takahiko; Ohtsu, Masaya; Murakami, Yasufumi

2012-01-01

Highlights: ► Depletion of hINO80 significantly reduced PCNA ubiquitination. ► Depletion of hINO80 significantly reduced nuclear dots intensity of RAD18 after UV irradiation. ► Western blot analyses showed phosphorylated hINO80 C-terminus. ► Overexpression of phosphorylation mutant hINO80 reduced PCNA ubiquitination. -- Abstract: Double strand breaks (DSBs) are the most serious type of DNA damage. DSBs can be generated directly by exposure to ionizing radiation or indirectly by replication fork collapse. The DNA damage tolerance pathway, which is conserved from bacteria to humans, prevents this collapse by overcoming replication blockages. The INO80 chromatin remodeling complex plays an important role in the DNA damage response. The yeast INO80 complex participates in the DNA damage tolerance pathway. The mechanisms regulating yINO80 complex are not fully understood, but yeast INO80 complex are necessary for efficient proliferating cell nuclear antigen (PCNA) ubiquitination and for recruitment of Rad18 to replication forks. In contrast, the function of the mammalian INO80 complex in DNA damage tolerance is less clear. Here, we show that human INO80 was necessary for PCNA ubiquitination and recruitment of Rad18 to DNA damage sites. Moreover, the C-terminal region of human INO80 was phosphorylated, and overexpression of a phosphorylation-deficient mutant of human INO80 resulted in decreased ubiquitination of PCNA during DNA replication. These results suggest that the human INO80 complex, like the yeast complex, was involved in the DNA damage tolerance pathway and that phosphorylation of human INO80 was involved in the DNA damage tolerance pathway. These findings provide new insights into the DNA damage tolerance pathway in mammalian cells.

Transit traverse in Missouri, 1900-1937. Part 5, Southwestern Missouri, 1900-37

Science.gov (United States)

Staack, John G.

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.Southwestern Missouri, as the term is used in this bulletin and as the subject of part 5 of the bulletin, is that section of the State lying south of latitude 38°00' and west of longitude 93°00'.

Transit traverse in Missouri, 1900-1937. Part 7, Central Missouri, 1902-37

Science.gov (United States)

Staack, John George

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.Central Missouri, as the term is used in this bulletin and as the subject of part 7 of the bulletin, is that section of the State lying between latitudes 36°00' and 39°30' and between longitudes 92°00' and 93°30'.

Transit traverse in Missouri, 1900-1937. Part 4, Northwestern Missouri, 1911-37

Science.gov (United States)

Staack, John G.

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.Northwestern Missouri, as the term is used in this bulletin and as the subject of part 4 of the bulletin, is that section of the State lying north of latitude 39°30' and west of longitude 93°15'

Enhancing fuzzy robot navigation systems by mimicking human visual perception of natural terrain traversibility

Science.gov (United States)

Tunstel, E.; Howard, A.; Edwards, D.; Carlson, A.

2001-01-01

This paper presents a technique for learning to assess terrain traversability for outdoor mobile robot navigation using human-embedded logic and real-time perception of terrain features extracted from image data.

Radiation activation of transcription factors in mammalian cells

International Nuclear Information System (INIS)

Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

1990-01-01

In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

A morphological comparison of narrow, low-gradient streams traversing wetland environments to alluvial streams.

Science.gov (United States)

Jurmu, Michael C

2002-12-01

Twelve morphological features from research on alluvial streams are compared in four narrow, low-gradient wetland streams located in different geographic regions (Connecticut, Indiana, and Wisconsin, USA). All four reaches differed in morphological characteristics in five of the features compared (consistent bend width, bend cross-sectional shape, riffle width compared to pool width, greatest width directly downstream of riffles, and thalweg location), while three reaches differed in two comparisons (mean radius of curvature to width ratio and axial wavelength to width ratio). The remaining five features compared had at least one reach where different characteristics existed. This indicates the possibility of varying morphology for streams traversing wetland areas further supporting the concept that the unique qualities of wetland environments might also influence the controls on fluvial dynamics and the development of streams. If certain morphological features found in streams traversing wetland areas differ from current fluvial principles, then these varying features should be incorporated into future wetland stream design and creation projects. The results warrant further research on other streams traversing wetlands to determine if streams in these environments contain unique morphology and further investigation of the impact of low-energy fluvial processes on morphological development. Possible explanations for the morphology deviations in the study streams and some suggestions for stream design in wetland areas based upon the results and field observations are also presented.

SEPT12–NDC1 Complexes Are Required for Mammalian Spermiogenesis

Directory of Open Access Journals (Sweden)

Tsung-Hsuan Lai

2016-11-01

Full Text Available Male factor infertility accounts for approximately 50 percent of infertile couples. The male factor-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile sperm, immature sperm, abnormally structured sperm, and sperm with nuclear damage. Our knockout and knock-in mice models demonstrated that SEPTIN12 (SEPT12 is vital for the formation of sperm morphological characteristics during spermiogenesis. In the clinical aspect, mutated SEPT12 in men results in oligozoospermia or teratozoospermia or both. Sperm with mutated SEPT12 revealed abnormal head and tail structures, decreased chromosomal condensation, and nuclear damage. Furthermore, several nuclear or nuclear membrane-related proteins have been identified as SEPT12 interactors through the yeast 2-hybrid system, including NDC1 transmembrane nucleoporin (NDC1. NDC1 is a major nuclear pore protein, and is critical for nuclear pore complex assembly and nuclear morphology maintenance in mammalian cells. Mutated NDC1 cause gametogenesis defects and skeletal malformations in mice, which were detected spontaneously in the A/J strain. In this study, we characterized the functional effects of SEPT12–NDC1 complexes during mammalian spermiogenesis. In mature human spermatozoa, SEPT12 and NDC1 are majorly colocalized in the centrosome regions; however, NDC1 is only slightly co-expressed with SEPT12 at the annulus of the sperm tail. In addition, SEPT12 interacts with NDC1 in the male germ cell line through coimmunoprecipitation. During murine spermiogenesis, we observed that NDC1 was located at the nuclear membrane of spermatids and at the necks of mature spermatozoa. In male germ cell lines, NDC1 overexpression restricted the localization of SEPT12 to the nucleus and repressed the filament formation of SEPT12. In mice sperm with mutated SEPT12, NDC1 dispersed around the manchette region of the sperm head and annulus, compared with concentrating at the sperm neck

Peano—A Traversal and Storage Scheme for Octree-Like Adaptive Cartesian Multiscale Grids

KAUST Repository

Weinzierl, Tobias; Mehl, Miriam

2011-01-01

-dimensional Cartesian grids represented by a (k = 3)- spacetree, a generalization of the well-known octree concept, and it also shows the correctness of the approach. These grids may change their adaptive structure throughout the traversal. The algorithm uses 2d + 4

Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

Science.gov (United States)

Guthrie, O'neil W

2017-10-01

In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

A biography and obituary of Alfred Traverse (1925–2015)

OpenAIRE

Riding, James B.; Chaloner FRS, William G.; Farley, Martin B.; Rich, Fredrick J.; Strother, Paul K.

2016-01-01

Professor Alfred (‘Al’) Traverse passed away following a long illness at 90 years of age on September 15th 2015 at Juniper Village, State College, Pennsylvania, USA. With his death, the twin sciences of palaeobotany and palynology have lost one of their most influential and productive of practitioners and teachers. He had a stellar student career, was a coal petrologist, an industrial palynologist and held parallel positions in the Episcopal (Anglican) church. However he is principally define...

Effects of an Arctic Ocean Ski Traverse on the Protective Capabilities of Expedition Footwear

National Research Council Canada - National Science Library

Endrusick, Thomas; Frykman, Peter; O'Brien, Catherine; Giblo, Joseph

2005-01-01

A traverse of the Arctic Ocean during a 2000-km unsupported ski expedition provided an opportunity to assess the impact of an extreme cold environment on the protective capabilities of a specialized footwear system (FS...

Sublethal damages: their nature and repair

Energy Technology Data Exchange (ETDEWEB)

Saenko, A.S.; Synzynys, B.I.; Trofimova, S.F. (Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii, Obninsk (USSR)); Gotlib, V.Ya.; Pelevina, I.I. (AN SSSR, Moscow. Inst. Khimicheskoj Fiziki)

1983-05-12

The molecular nature of sublethal damage (SLD) arising after ionizing irradiation of cultured mammalian cells was considered on the basis of data on DNA repair and cell recovery after SLD observed in lymphosarcoma cells as well as of literature data. The rate of SLD recovery and that of restoration of the cell's ability to initiate DNA synthesis were shown to be similar in new replicons. These data along with knowledge about the role of exchange type chromosomal aberrations in reproductive death permitted us to propose the hypothesis that conformational changes of chromatine - most probably, relaxation of condensed chromosomal material - are damage registered as SLD at the cellular level. Double-strand breaks and a slowly repaired part of DNA single-strand breaks are candidates for SLD.

Repair of DNA damage induced by ionizing radiation and benzo[a]pyrene in mammalian cells

International Nuclear Information System (INIS)

Cerutti, P.; Shinohara, K.; Remsen, J.

1977-01-01

The biological effects of DNA-damaging agents are codetermined by the structural characteristics of the lesions, the quality and extent of the local distortion of DNA and chromatin structure, and the mode(s) of damage processing used by a given type of cell. Persistent damage (i.e., damage that is not removed before it is reached by DNA replication) may be mostly responsible for mutagenesis and carcinogenesis. To understand the effects of environmental physical and chemical DNA-damaging agents on human health, the mechanisms of damage processing used by human cells have to be elucidated. We report our studies of the excision of gamma-ray products of the 5,6-dihydroxydihydrothymine type (t 0 /sub 2//sup γ/) in normal human fibroblasts and in fibroblasts from patients with the hereditary diseases Fanconi's anemia (FA) and ataxia telangiectasia (AT). Both diseases are characterized by chromosomal instability and increased susceptibility for the development of cancer. Formation and repair of DNA-benzo[a]pyrene adducts were studied in baby hamster kidney cells, secondary mouse embryo cells, and human lymphoma. The relative persistence of DNA-B[a]P may explain the high mutagenicity of the 7,8-dihydroxy-9,10-epoxy-tetrahydrobenzo[a]pyrene metabolites in rodent cells that has been observed by several investigators

Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

International Nuclear Information System (INIS)

Maga, J.A.

1983-01-01

The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

Dose-rate evidence for two kinds of radiation damage in stationary-phase mammalian cells

International Nuclear Information System (INIS)

Metting, N.F.; Braby, L.A.; Roesch, W.C.; Nelson, J.M.

1985-01-01

Survival based on colony formation was measured for starved plateau-phase Chinese hamster ovary (CHO) cells exposed to 250 kVp X rays at dose rates of 0.0031, 0.025, 0.18, 0.31, and 1.00 Gy/min. A large dose-rate effect was demonstrated. Delayed plating experiments and dose response experiments following a conditioning dose, both using a dose rate of 1.00 Gy/min and plating delays of up to 48 hr, were also used to investigate the alternative repair hypotheses. There is clearly a greater change in survival in dose-rate experiments than in the other experiments. Thus the authors believe that a process which depends on the square of the concentration of initial damage, and which alters the effect of initial damage on cell survival is being observed. They have applied the damage accumulation model to separate the single-event damage from this concentration-dependent form and estimate the repair rate for the latter type to be 70 min for their CHO cells

Transit traverse in Missouri, 1900-1937. Part 3, East-central Missouri, 1903-37

Science.gov (United States)

Staack, John George

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.East-central Missouri, as the term is used in this bulletin and as the subject of part 3 of the bulletin, is that section of the State lying between latitudes 38°00' and 39°15' and east of longitude 92°00'.

Transit traverse in Missouri, 1900-1937. Part 2, South-central Missouri, 1908-37

Science.gov (United States)

Staack, John George

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.South-central Missouri, as the term is used in this bulletin and as the subject of part 2 of the bulletin, is that section of the State lying south of latittude, 38°00' and between longitudes 91°15' and 93°00'.

Transit traverse in Missouri, 1900-1937. Part 8, West-central Missouri, 1906-37

Science.gov (United States)

Staack, John G.

1940-01-01

This bulletin, which for convenience is to be published in eight parts, contains the results of all transit traverse* done In Missouri through 1937 by the Geological Survey, United States Department of the Interior, including those heretofore published. (See page X.) Each of the parts deals with one of eight sections into which the State has been divided for this purpose and which have been designated northeastern, northwestern, southeastern, southwestern, central, east-central, south-central, and west-central Missouri. In each part descriptions of the points for which geodetic positions have been determined are listed according to the quadrangles in which the points occur. Results of transit traverse other than that done by the Geological Survey have not been included.West-central Missouri, as the term is used in this bulletin and as the subject of part 8 of the bulletin, is that section of the State lying between latitudes 38°00' and 39°30' and west of longitude 93°30'.

Traversable wormholes without exotic matter in multimetric repulsive gravity

Science.gov (United States)

Hohmann, Manuel

2014-04-01

We present a static, spherically symmetric, traversable wormhole solution to multimetric gravity which is sustained by only nonexotic matter, i.e., matter which satisfies all energy conditions. The possibility of this solution arises from the fact that under certain conditions the multimetric gravitational field equations reduce to the Einstein equations, but with a negative effective gravitational constant. We show that the Arnowitt-Deser-Misner mass of this wormhole vanishes, so that it appears massless to observers in the asymptotically flat spacetime. We finally speculate on the feasibility of creating and maintaining this type of wormhole by an advanced civilization.

Ionizing Radiation-Induced DNA Damage and Its Repair in Human Cells

Energy Technology Data Exchange (ETDEWEB)

Dizdaroglu, Miral

1999-05-12

DNA damage in mammalian chromatin in vitro and in cultured mammalian cells including human cells was studied. In the first phase of these studies, a cell culture laboratory was established. Necessary equipment including an incubator, a sterile laminar flow hood and several centrifuges was purchased. We have successfully grown several cell lines such as murine hybridoma cells, V79 cells and human K562 leukemia cells. This was followed by the establishment of a methodology for the isolation of chromatin from cells. This was a very important step, because a routine and successful isolation of chromatin was a prerequisite for the success of the further studies in this project, the aim of which was the measurement of DNA darnage in mammalian chromatin in vitro and in cultured cells. Chromatin isolation was accomplished using a slightly modified procedure of the one described by Mee & Adelstein (1981). For identification and quantitation of DNA damage in cells, analysis of chromatin was preferred over the analysis of "naked DNA" for the following reasons: i. DNA may not be extracted efficiently from nucleoprotein in exposed cells, due to formation of DNA-protein cross-links, ii. the extractability of DNA is well known to decrease with increasing doses of radiation, iii. portions of DNA may not be extracted due to fragmentation, iv. unextracted DNA may contain a significant portion of damaged DNA bases and DNA-protein cross-links. The technique of gas chromatography/mass spectrometry (GC/MS), which was used in the present project, permits the identification and quantitation of modified DNA bases in chromatin in the presence of proteins without the necessity of first isolating DNA from chromatin. This has been demonstrated previously by the results from our laboratory and by the results obtained during the course of the present project. The quality of isolated chromatin was tested by measurement of its content of DNA, proteins, and RNA, by analysis of its protein

Ionizing Radiation-Induced DNA Damage and Its Repair in Human Cells

International Nuclear Information System (INIS)

Dizdaroglu, Miral

1999-01-01

DNA damage in mammalian chromatin in vitro and in cultured mammalian cells including human cells was studied. In the first phase of these studies, a cell culture laboratory was established. Necessary equipment including an incubator, a sterile laminar flow hood and several centrifuges was purchased. We have successfully grown several cell lines such as murine hybridoma cells, V79 cells and human K562 leukemia cells. This was followed by the establishment of a methodology for the isolation of chromatin from cells. This was a very important step, because a routine and successful isolation of chromatin was a prerequisite for the success of the further studies in this project, the aim of which was the measurement of DNA darnage in mammalian chromatin in vitro and in cultured cells. Chromatin isolation was accomplished using a slightly modified procedure of the one described by Mee ampersand Adelstein (1981). For identification and quantitation of DNA damage in cells, analysis of chromatin was preferred over the analysis of ''naked DNA'' for the following reasons: i. DNA may not be extracted efficiently from nucleoprotein in exposed cells, due to formation of DNA-protein cross-links, ii. the extractability of DNA is well known to decrease with increasing doses of radiation, iii. portions of DNA may not be extracted due to fragmentation, iv. unextracted DNA may contain a significant portion of damaged DNA bases and DNA-protein cross-links. The technique of gas chromatography/mass spectrometry (GC/MS), which was used in the present project, permits the identification and quantitation of modified DNA bases in chromatin in the presence of proteins without the necessity of first isolating DNA from chromatin. This has been demonstrated previously by the results from our laboratory and by the results obtained during the course of the present project. The quality of isolated chromatin was tested by measurement of its content of DNA, proteins, and RNA, by analysis of its protein

The Traverse Planning Process for the Drats 2010 Analog Field Simulations

Science.gov (United States)

Horz, Friedrich; Gruener, John; Lofgren, Gary; Skinner, James A., Jr.; Graf, Jodi; Seibert, Marc

2011-01-01

Traverse planning concentrates on optimizing the science return within the overall objectives of planetary surface missions or their analog field simulations. Such simulations were conducted in the San Francisco Volcanic Field, northern Arizona, from Aug. 26 to Sept 17, 2010 and involved some 200 individuals in the field, with some 40 geoscientists composing the science team. The purpose of these Desert Research and Technology Studies (DRATS) is to exercise and evaluate developmental hardware, software and operational concepts in a mission-like, fully-integrated, setting under the direction of an onsite Mobile Mission Control Center(MMCC). DRATS 2010 focused on the simultaneous operation of 2 rovers, a historic first. Each vehicle was manned by an astronaut-commander and an experienced field geologist. Having 2 rovers and crews in the field mandated substantially more complex science and mission control operations compared to the single rover DRATS tests of 2008 and 2009, or the Apollo lunar missions. For instance, the science support function was distributed over 2 "back rooms", one for each rover, with both "tactical" teams operating independently and simultaneously during the actual traverses. Synthesis and integration of the daily findings and forward planning for the next day(s) was accomplished overnight by yet another "strategic" science team.

Enhancer evolution across 20 mammalian species

DEFF Research Database (Denmark)

Villar, Diego; Berthelot, Camille; Aldridge, Sarah

2015-01-01

The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

Response-only method for damage detection of beam-like structures using high accuracy frequencies with auxiliary mass spatial probing

Science.gov (United States)

Zhong, Shuncong; Oyadiji, S. Olutunde; Ding, Kang

2008-04-01

This paper proposes a new approach based on auxiliary mass spatial probing using spectral centre correction method (SCCM), to provide a simple solution for damage detection by just using the response time history of beam-like structures. The natural frequencies of a damaged beam with a traversing auxiliary mass change due to change in the inertia of the beam as the auxiliary mass is traversed along the beam, as well as the point-to-point variations in the flexibility of the beam. Therefore the auxiliary mass can enhance the effects of the crack on the dynamics of the beam and, therefore, facilitate the identification and location of damage in the beam. That is, the auxiliary mass can be used to probe the dynamic characteristic of the beam by traversing the mass from one end of the beam to the other. However, it is impossible to obtain accurate modal frequencies by the direct operation of the fast Fourier transform (FFT) of the response data of the structure because the frequency spectrum can be only calculated from limited sampled time data which results in the well-known leakage effect. SCCM is identical to the energy centrobaric correction method (ECCM) which is a practical and effective method used in rotating mechanical fault diagnosis and which resolves the shortcoming of FFT and can provide high accuracy estimate of frequency, amplitude and phase. In the present work, the modal responses of damaged simply supported beams with auxiliary mass are computed using the finite element method (FEM). The graphical plots of the natural frequencies calculated by SCCM versus axial location of auxiliary mass are obtained. However, it is difficult to locate the crack directly from the curve of natural frequencies. A simple and fast method, the derivatives of natural frequency curve, is proposed in the paper which can provide crack information for damage detection of beam-like structures. The efficiency and practicability of the proposed method is illustrated via numerical

Liv. 52 protection against radiation induced lesions in mammalian liver

International Nuclear Information System (INIS)

Saini, M.R.; Saini, N.

1985-01-01

Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

Genotoxic damage in non-irradiated cells: contribution from the bystander effect

International Nuclear Information System (INIS)

Zhou, H.; Randers-Pherson, G.; Suzuki, M.; Waldren, C.A.; Hei, T.K.

2002-01-01

It has always been accepted dogma that the deleterious effects of ionising radiation such as mutagenesis and carcinogenesis are due mainly to direct damage to DNA. Using the Columbia University charged-particle microbeam and the highly sensitive A L cell mutagenic assay, it is shown here that non-irradiated cells acquire the mutagenic phenotype through direct contact with cells whose nuclei are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a gap junction inhibitor, significantly decreased the mutant yield. Furthermore, when irradiated cells were mixed with control cells in a similar ration as the in situ studies, no enhancement in bystander mutagenesis was detected. Our studies provide clear evidence that genotoxic damage can be induced in non-irradiated cells, and that gap junction mediated cell-cell communication plays a critical role in the bystander phenomenon. (author)

Kevin Traverse-Healy: kommunikatsiooni eesmärk on muuta käitumist / intervjueerinud Annela Laaneots

Index Scriptorium Estoniae

Traverse-Healy, Kevin

2013-01-01

Intervjuu strateegianõuniku ja rahvusvaheliselt tuntud kommunikatsioonieksperdi Kevin Traverse-Healyga, kes peab eduka kommunikatsioonijuhi töös oluliseks luua õige kommunikatsioon, mille eesmärgiks on sihtrühma käitumise muutus

Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

International Nuclear Information System (INIS)

Wan Jin; Zheng Hua; Xiao Honglei; She Zhenjue; Zhou Guomin

2007-01-01

Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results provide evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons

Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

Energy Technology Data Exchange (ETDEWEB)

Jin, Wan; Hua, Zheng; Honglei, Xiao; Zhenjue, She [Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai (China); Zhou Guomin [Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai (China)], E-mail: gmzhou185@yahoo.com.cn

2007-11-16

Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results provide evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons.

Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

Directory of Open Access Journals (Sweden)

Tarikul Huda Mazumder

Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells. Emphasis on DNA double strand breaks and chromatin breaks

Science.gov (United States)

Lett, J. T.

1992-01-01

For several years, it has been evident that cellular radiation biology is in a necessary period of consolidation and transition (Lett 1987, 1990; Lett et al. 1986, 1987). Both changes are moving apace, and have been stimulated by studies with heavy charged particles. From the standpoint of radiation chemistry, there is now a consensus of opinion that the DNA hydration shell must be distinguished from bulk water in the cell nucleus and treated as an integral part of DNA (chromatin) (Lett 1987). Concomitantly, sentiment is strengthening for the abandonment of the classical notions of "direct" and "indirect" action (Fielden and O'Neill 1991; O'Neill 1991; O'Neill et al. 1991; Schulte-Frohlinde and Bothe 1991 and references therein). A layer of water molecules outside, or in the outer edge of, the DNA (chromatin) hydration shell influences cellular radiosensitivity in ways not fully understood. Charge and energy transfer processes facilitated by, or involving, DNA hydration must be considered in rigorous theories of radiation action on cells. The induction and processing of double stand breaks (DSBs) in DNA (chromatin) seem to be the predominant determinants of the radiotoxicity of normally radioresistant mammalian cells, the survival curves of which reflect the patterns of damage induced and the damage present after processing ceases, and can be modelled in formal terms by the use of reaction (enzyme) kinetics. Incongruities such as sublethal damage are neither scientifically sound nor relevant to cellular radiation biology (Calkins 1991; Lett 1990; Lett et al. 1987a). Increases in linear energy transfer (LET infinity) up to 100-200 keV micron-1 cause increases in the extents of neighboring chemical and physical damage in DNA denoted by the general term DSB. Those changes are accompanied by decreasing abilities of cells normally radioresistant to sparsely ionizing radiations to process DSBs in DNA and chromatin and to recover from radiation exposure, so they make

Mapping, Navigation, and Learning for Off-Road Traversal

DEFF Research Database (Denmark)

Konolige, Kurt; Agrawal, Motilal; Blas, Morten Rufus

2009-01-01

The challenge in the DARPA Learning Applied to Ground Robots (LAGR) project is to autonomously navigate a small robot using stereo vision as the main sensor. During this project, we demonstrated a complete autonomous system for off-road navigation in unstructured environments, using stereo vision......, online terrain traversability learning, visual odometry, map registration, planning, and control. At the end of 3 years, the system we developed outperformed all nine other teams in final blind tests over previously unseen terrain.......The challenge in the DARPA Learning Applied to Ground Robots (LAGR) project is to autonomously navigate a small robot using stereo vision as the main sensor. During this project, we demonstrated a complete autonomous system for off-road navigation in unstructured environments, using stereo vision...

Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage

OpenAIRE

Zhang, Pan; Herbig, Utz; Coffman, Frederick; Lambert, Muriel W.

2013-01-01

Telomere integrity is critical for telomere function and genomic stability. We previously demonstrated that non-erythroid ?-spectrin (?IISp) is present in mammalian cell nuclei where it is important in repair of DNA interstrand cross-links (ICLs) and chromosome stability. We now demonstrate that ?IISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recrui...

Cockroaches traverse crevices, crawl rapidly in confined spaces, and inspire a soft, legged robot

Science.gov (United States)

Jayaram, Kaushik; Full, Robert J.

2016-01-01

Jointed exoskeletons permit rapid appendage-driven locomotion but retain the soft-bodied, shape-changing ability to explore confined environments. We challenged cockroaches with horizontal crevices smaller than a quarter of their standing body height. Cockroaches rapidly traversed crevices in 300–800 ms by compressing their body 40–60%. High-speed videography revealed crevice negotiation to be a complex, discontinuous maneuver. After traversing horizontal crevices to enter a vertically confined space, cockroaches crawled at velocities approaching 60 cm⋅s−1, despite body compression and postural changes. Running velocity, stride length, and stride period only decreased at the smallest crevice height (4 mm), whereas slipping and the probability of zigzag paths increased. To explain confined-space running performance limits, we altered ceiling and ground friction. Increased ceiling friction decreased velocity by decreasing stride length and increasing slipping. Increased ground friction resulted in velocity and stride length attaining a maximum at intermediate friction levels. These data support a model of an unexplored mode of locomotion—“body-friction legged crawling” with body drag, friction-dominated leg thrust, but no media flow as in air, water, or sand. To define the limits of body compression in confined spaces, we conducted dynamic compressive cycle tests on living animals. Exoskeletal strength allowed cockroaches to withstand forces 300 times body weight when traversing the smallest crevices and up to nearly 900 times body weight without injury. Cockroach exoskeletons provided biological inspiration for the manufacture of an origami-style, soft, legged robot that can locomote rapidly in both open and confined spaces. PMID:26858443

Traversing the Cell: Agrobacterium T-DNA’s Journey to the Host Genome

Science.gov (United States)

Gelvin, Stanton B.

2012-01-01

The genus Agrobacterium is unique in its ability to conduct interkingdom genetic exchange. Virulent Agrobacterium strains transfer single-strand forms of T-DNA (T-strands) and several Virulence effector proteins through a bacterial type IV secretion system into plant host cells. T-strands must traverse the plant wall and plasma membrane, traffic through the cytoplasm, enter the nucleus, and ultimately target host chromatin for stable integration. Because any DNA sequence placed between T-DNA “borders” can be transferred to plants and integrated into the plant genome, the transfer and intracellular trafficking processes must be mediated by bacterial and host proteins that form complexes with T-strands. This review summarizes current knowledge of proteins that interact with T-strands in the plant cell, and discusses several models of T-complex (T-strand and associated proteins) trafficking. A detailed understanding of how these macromolecular complexes enter the host cell and traverse the plant cytoplasm will require development of novel technologies to follow molecules from their bacterial site of synthesis into the plant cell, and how these transferred molecules interact with host proteins and sub-cellular structures within the host cytoplasm and nucleus. PMID:22645590

Traversable wormholes satisfying the weak energy condition in third-order Lovelock gravity

Science.gov (United States)

Zangeneh, Mahdi Kord; Lobo, Francisco S. N.; Dehghani, Mohammad Hossein

2015-12-01

In this paper, we consider third-order Lovelock gravity with a cosmological constant term in an n -dimensional spacetime M4×Kn -4, where Kn -4 is a constant curvature space. We decompose the equations of motion to four and higher dimensional ones and find wormhole solutions by considering a vacuum Kn -4 space. Applying the latter constraint, we determine the second- and third-order Lovelock coefficients and the cosmological constant in terms of specific parameters of the model, such as the size of the extra dimensions. Using the obtained Lovelock coefficients and Λ , we obtain the four-dimensional matter distribution threading the wormhole. Furthermore, by considering the zero tidal force case and a specific equation of state, given by ρ =(γ p -τ )/[ω (1 +γ )], we find the exact solution for the shape function which represents both asymptotically flat and nonflat wormhole solutions. We show explicitly that these wormhole solutions in addition to traversibility satisfy the energy conditions for suitable choices of parameters and that the existence of a limited spherically symmetric traversable wormhole with normal matter in a four-dimensional spacetime implies a negative effective cosmological constant.

Mammalian synthetic biology: emerging medical applications.

Science.gov (United States)

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

2015-05-06

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Mammalian development in space

Science.gov (United States)

Ronca, April E.

2003-01-01

Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

Obstacle traversal and self-righting of bio-inspired robots reveal the physics of multi-modal locomotion

Science.gov (United States)

Li, Chen; Fearing, Ronald; Full, Robert

Most animals move in nature in a variety of locomotor modes. For example, to traverse obstacles like dense vegetation, cockroaches can climb over, push across, reorient their bodies to maneuver through slits, or even transition among these modes forming diverse locomotor pathways; if flipped over, they can also self-right using wings or legs to generate body pitch or roll. By contrast, most locomotion studies have focused on a single mode such as running, walking, or jumping, and robots are still far from capable of life-like, robust, multi-modal locomotion in the real world. Here, we present two recent studies using bio-inspired robots, together with new locomotion energy landscapes derived from locomotor-environment interaction physics, to begin to understand the physics of multi-modal locomotion. (1) Our experiment of a cockroach-inspired legged robot traversing grass-like beam obstacles reveals that, with a terradynamically ``streamlined'' rounded body like that of the insect, robot traversal becomes more probable by accessing locomotor pathways that overcome lower potential energy barriers. (2) Our experiment of a cockroach-inspired self-righting robot further suggests that body vibrations are crucial for exploring locomotion energy landscapes and reaching lower barrier pathways. Finally, we posit that our new framework of locomotion energy landscapes holds promise to better understand and predict multi-modal biological and robotic movement.

Spatial Variability of Perchlorate along a Traverse Route from Zhongshan Station to Dome A, East Antarctica

Science.gov (United States)

Jiang, S.; Cole-Dai, J.; Li, Y.; An, C.

2016-12-01

Snow deposition and accumulation on the Antarctic ice sheet preserve records of climatic change, as well as those of chemical characteristics of the environment. Chemical composition of snow and ice cores can be used to track the sources of important substances including pollutants and to investigate relationships between atmospheric chemistry and climatic conditions. Recent development in analytical methodology has enabled the determination of ultra-trace levels of perchlorate in polar snow. We have measured perchlorate concentrations in surface snow samples collected along a traverse route from Zhongshan Station to Dome A in East Antarctica to determine the level of atmospheric perchlorate in East Antarctica and to assess the spatial variability of perchlorate along the traverse route. Results show that the perchlorate concentrations vary between 32 and 200 ng kg-1, with an average of 104.3 ng kg-1. And perchlorate concentration profile presents regional variation patterns along the traverse route. In the coastal region, perchlorate concentration displays an apparent decreasing relationship with increasing distance inland; it exhibits no apparent trend in the intermediate region from 200 to 1000 km. The inland region from 1000 to 1244 km presents a generally increasing trend of perchlorate concentration approaching the dome. Different rates of atmospheric production, dilution by snow accumulation and re-deposition of snow-emitted perchlorate (post-depositional change) are the three possible factors influencing the spatial variability of perchlorate over Antarctica.

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

Directory of Open Access Journals (Sweden)

Liliana Costa

2012-06-01

Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

Autophagy in DNA Damage Response

Directory of Open Access Journals (Sweden)

Piotr Czarny

2015-01-01

Full Text Available DNA damage response (DDR involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1. mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADPribose polymerase 1 (PARP-1, Mre11–Rad50–Nbs1 (MRN complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy.

Predicting Long-Range Traversability from Short-Range Stereo-Derived Geometry

Science.gov (United States)

Turmon, Michael; Tang, Benyang; Howard, Andrew; Brjaracharya, Max

2010-01-01

Based only on its appearance in imagery, this program uses close-range 3D terrain analysis to produce training data sufficient to estimate the traversability of terrain beyond 3D sensing range. This approach is called learning from stereo (LFS). In effect, the software transfers knowledge from middle distances, where 3D geometry provides training cues, into the far field where only appearance is available. This is a viable approach because the same obstacle classes, and sometimes the same obstacles, are typically present in the mid-field and the farfield. Learning thus extends the effective look-ahead distance of the sensors.

Damage and repair in mammalian cells after exposure to non-ionizing radiations. 1

International Nuclear Information System (INIS)

Harm, H.

1978-01-01

Cornea cells of the rat kangaroo or 'potoroo' (Potorous tridactylus) were exposed to far-UV (254 or 302 nm) radiation, with or without subsequent illumination by near-UV or visible light. The DNA of these cells was extracted and tested for the presence of photoproducts binding yeast photoreactivating enzyme (PRE). The effects on repair kinetics of the transforming DNA indicate that in UV-irradiated potoroo cornea cells up to approximately 90% of photorepairable DNA damage can be photorepaired within 15 min. However, the extent of cellular photorepair depends appreciably on experimental parameters during photoreactivating treatment, including the spectral composition of photoreactivating light. Apparently superposition of damage by the photoreactivating treatment itself is the critical factor. This may explain experimental discrepancies existing in different laboratories studying photorepair in UV-irradiated cells of placental mammals. (Auth.)

Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites

International Nuclear Information System (INIS)

Lenz, J.; Okenquist, S.A.; LoSardo, J.E.; Hamilton, K.K.; Doetsch, P.W.

1990-01-01

Damage to DNA can have lethal or mutagenic consequences for cells unless it is detected and repaired by cellular proteins. Repair depends on the ability of cellular factors to distinguish the damaged sites. Electrophoretic binding assays were used to identify a factor from the nuclei of mammalian cells that bound to DNA containing apurinic sites. A binding assay based on the use of β-galactosidase fusion proteins was subsequently used to isolate recombinant clones of human cDNAs that encoded apurinic DNA-binding proteins. Two distinct human cDNAs were identified that encoded proteins that bound apurinic DNA preferentially over undamaged, methylated, or UV-irradiated DNA. These approaches may offer a general method for the detection of proteins that recognize various types of DNA damage and for the cloning of genes encoding such proteins

Radiation- induced aneuploidy in mammalian germ cells

International Nuclear Information System (INIS)

Tease, C.

1989-01-01

The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

Relationship between radiation damage on biomembranes and the cell killing

International Nuclear Information System (INIS)

Sato, Chikako

1978-01-01

Death of unproliferated mammalian erythrocytes causes an increase of ion permeability as membranous damage after x-ray irradiation and hemolysis, and production of peroxides in membrane and an effect of SH base are thought as the causes. As a mechanism of death of small lymphocytes with high radiosensitivity, the following three assumptions were reported: disorder of ATP synthesis in nucleus and cytoplasms, self-digestion by flowing out of proteinase from lysozyme by membranous disorder, and catalysis of DNA-protein complex. Death of proliferated cells causes loss of colony formation ability, and it was explained by colony method using Escherichia coli and mammalian cells and by dose-survival rate. Changes in membranous structure by cellular electrophoretic degree and the relationship between these changes and inhibition of cellular proliferation were mentioned as problems. (Tsunoda, M.)

Magnetic investigations along selected high-resolution seismic traverses in the central block of Yucca Mountain, Nevada

International Nuclear Information System (INIS)

Ponce, D.A.; Sikora, R.F.; Roberts, C.W.; Morin, R.L.; Halvorson, P.F.

1995-01-01

Ground magnetic data collected along several traverses across the central block of Yucca Mountain in southwest Nevada are interpreted. These data were collected as part of an effort to evaluate faulting in the vicinity of a potential nuclear waste repository at Yucca Mountain. Magnetic data and models along traverses across the central block of Yucca Mountain reveal anomalies associated with known faults and indicate a number of possible concealed faults beneath the eastern flank of Yucca Mountain. The central part of the eastern flank of Yucca Mountain is characterized by numerous small-amplitude anomalies that probably reflect small-scale faulting. Magnetic modeling of the terrain along the eastern flank of Yucca Mountain indicates that terrain induced magnetic anomalies of about 100 to 150 nT are present along some profiles where steep terrain exists above the magnetometer

Proposing an International Collaboration on Lightweight Autonomous Vehicles to Conduct Scientific Traverses and Surveys over Antarctica and the Surrounding Sea Ice

Science.gov (United States)

Carsey, Frank; Behar, Alberto

2004-01-01

We have continued to develop a concept for use of autonomous rovers, originally developed for use in planetary exploration, in polar science on Earth; the concept was the subject of a workshop, and this report summarizes and extends that workshop. The workshop on Antarctic Autonomous Scientific Vehicles and Traverses met at the National Geographic Society on February 14 and 15, 2001 to discuss scientific objectives and benefits of the use of autonomous rovers. The participants enthusiastically viewed rovers as being uniquely valuable for such tasks as data taking on tedious or repetitive routes, traverses in polar night, difficult or hazardous routes, extremely remote regions, routes requiring only simple instrumentation, traverses that must be conducted at low speed, augments of manned traverses, and scientific procedures not compatible with human presence or combustion engines. The workshop has concluded that instrumented autonomous vehicles, of the type being developed for planetary exploration, have the potential to contribute significantly to the way science in conducted in Antarctica while also aiding planetary technology development, and engaging the public's interest. Specific objectives can be supported in understanding ice sheet mass balance, sea ice heat and momentum exchange, and surface air chemistry processes. In the interval since the workshop, we have concluded that organized program to employ such rovers to perform scientific tasks in the Fourth International Polar Year would serve the objectives of that program well.

Enhancer Evolution across 20 Mammalian Species

Science.gov (United States)

Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

2015-01-01

Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

Mammalian gastrointestinal parasites in rainforest remnants

Indian Academy of Sciences (India)

Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

Trans-Splenic Portal Vein Embolization: A Technique to Avoid Damage to the Future Liver Remnant

International Nuclear Information System (INIS)

Sarwar, Ammar; Brook, Olga R.; Weinstein, Jeffrey L.; Khwaja, Khalid; Ahmed, Muneeb

2016-01-01

Portal vein embolization (PVE) induces hypertrophy of the future liver remnant (FLR) in patients undergoing extensive hepatic resection. Portal vein access for PVE via the ipsilateral hepatic lobe (designated for resection) places veins targeted for embolization at acute angles to the access site requiring reverse curve catheters for access. This approach also involves access close to tumors in the ipsilateral lobe and requires care to avoid traversing tumor. Alternatively, a contralateral approach (through the FLR) risks damage to the FLR due to iatrogenic trauma or non-target embolization. Two patients successfully underwent PVE via trans-splenic portal vein access, allowing easy access to the ipsilateral portal veins and eliminating risk of damage to FLR. Technique and advantages of trans-splenic portal vein access to perform PVE are described.

Trans-Splenic Portal Vein Embolization: A Technique to Avoid Damage to the Future Liver Remnant

Energy Technology Data Exchange (ETDEWEB)

Sarwar, Ammar, E-mail: asarwar@bidmc.harvard.edu; Brook, Olga R.; Weinstein, Jeffrey L. [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Interventional Radiology, Department of Radiology (United States); Khwaja, Khalid [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Transplant Surgery, Department of Surgery (United States); Ahmed, Muneeb [Beth Israel Deaconess Medical Center/Harvard Medical School, Division of Interventional Radiology, Department of Radiology (United States)

2016-10-15

Portal vein embolization (PVE) induces hypertrophy of the future liver remnant (FLR) in patients undergoing extensive hepatic resection. Portal vein access for PVE via the ipsilateral hepatic lobe (designated for resection) places veins targeted for embolization at acute angles to the access site requiring reverse curve catheters for access. This approach also involves access close to tumors in the ipsilateral lobe and requires care to avoid traversing tumor. Alternatively, a contralateral approach (through the FLR) risks damage to the FLR due to iatrogenic trauma or non-target embolization. Two patients successfully underwent PVE via trans-splenic portal vein access, allowing easy access to the ipsilateral portal veins and eliminating risk of damage to FLR. Technique and advantages of trans-splenic portal vein access to perform PVE are described.

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

International Nuclear Information System (INIS)

Feinendegen, L.E.; Sondhaus, C.A.; Altman, K.I.

1998-01-01

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

1998-12-31

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

Localization of two mammalian cyclin dependent kinases during mammalian meiosis

NARCIS (Netherlands)

Ashley, T.; Walpita, D.; de rooij, D. G.

2001-01-01

Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

Rapid and preferential activation of the c-jun gene during the mammalian UV response

International Nuclear Information System (INIS)

Devary, Y.; Gottlieb, R.A.; Lau, L.F.; Karin, M.

1991-01-01

Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage-inducible genes such as human collagenase

Mechanical Properties and Wear Behavior of AA5182/WC Nanocomposite Fabricated by Friction Stir Welding at Different Tool Traverse Speeds

Science.gov (United States)

Paidar, Moslem; Asgari, Ali; Ojo, Olatunji Oladimeji; Saberi, Abbas

2018-03-01

Grain growth inhibition at the heat-affected zone, improved weld strength and superior tribological properties of welds are desirable attributes of modern manufacturing. With the focused on these attributes, tungsten carbide (WC) nanoparticles were employed as reinforcements for the friction stir welding of 5-mm-thick AA5182 aluminum alloy by varying tool traverse speeds. The microstructure, microhardness, ultimate tensile strength, fracture and wear behavior of the resultant WC-reinforced welds were investigated, while unreinforced AA5182 welds were employed as controls for the study. The result shows that the addition of WC nanoparticles causes substantial grain refinement within the weld nugget. A decrease in traverse speed caused additional particle fragmentation, improved hardness value and enhanced weld strength in the reinforced welds. Improved wear rate and friction coefficient of welds were attained at a reduced traverse speed of 100 mm/min in the WC-reinforced welds. This improvement is attributed to the effects of reduced grain size/grain fragmentation and homogeneous dispersion of WC nanoparticles within the WC-reinforced weld nugget.

Radiation induced damage to the lipid contents of bacteria and cultured mammalian cells

International Nuclear Information System (INIS)

Gholipour Khalili, K.

1993-01-01

In this study, exponentially growing phase of E. Coli. K12-N167 and cultured mouse leukemic L5178Y were used to study the effect of gamma irradiation on phospholipid contents. Following irradiation, both bacteria and cultured cells were incubated with either 14 C or 32 P labelled precursors for periods of cell division time. Phospholipid composition and their contents were detected in both the bacteria and cultured cells by using liquid scintillation counting and autoradiography methods. In contrast, as radiation dose increased, the Phospholipid contents were decreased in the both bacteria and cultured cells. It was concluded that the changes of phospholipid contents may result to altered activities of phospholipid pathway enzymes damaged by a radiation dose. The results of this investigation would be helpful in control of induced radiation damages in cell killings in radiation workers and radiation treatment of human cancer in the clinics. (author). 35 refs, 3 figs, 4 tabs

Plasticity within stem cell hierarchies in mammalian epithelia.

Science.gov (United States)

Tetteh, Paul W; Farin, Henner F; Clevers, Hans

2015-02-01

Tissue homeostasis and regeneration are fueled by resident stem cells that have the capacity to self-renew, and to generate all the differentiated cell types that characterize a particular tissue. Classical models of such cellular hierarchies propose that commitment and differentiation occur unidirectionally, with the arrows 'pointing away' from the stem cell. Recent studies, all based on genetic lineage tracing, describe various strategies employed by epithelial stem cell hierarchies to replace damaged or lost cells. While transdifferentiation from one tissue type into another ('metaplasia') appears to be generally forbidden in nonpathological contexts, plasticity within an individual tissue stem cell hierarchy may be much more common than previously appreciated. In this review, we discuss recent examples of such plasticity in selected mammalian epithelia, highlighting the different modes of regeneration and their implications for our understanding of cellular hierarchy and tissue self-renewal. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamics of radioecological and genetic processes in populations of mammalian model species at contamination of ecosystems

International Nuclear Information System (INIS)

Ryabokon', N.I.; Goncharova, R.I.

2008-01-01

A short review of data on the time course of radiobiological and genetic processes in natural populations of mammalian model species inhabiting radiocontaminated ecosystems over many generations is presented here. The described time-courses of biological end-points in these populations do not reflect the time course of the whole-body dose rates, but do the outcome of multiple processes, including the direct response to individual irradiation, the transgeneration transmission and accumulation of induced damages and the development of adaptation. (authors)

Modification of radiation damage by naturally occurring substances

International Nuclear Information System (INIS)

Prasad, K.N.

1984-01-01

The major objectives of studying the modification of radiation sensitivity have been (1) to identify a compound that will produce a differential protection or sensitization of the effect of irradiation on normal and tumor tissue, and (2) to understand more about the mechanisms of radiation damage. In spite of massive research on this particular problem since World War II, the first objective remains elusive. During this period, numerous radioprotective and radiosensitizing agents have been identified. These agents have served as important biologic tools for increasing our understanding of radiation injuries. Most of these substances are synthetic compounds and are very toxic to humans. In addition, very few of the compounds provide differential modifications of the effect of radiation on tumor and normal cells. This chapter presents objectives for identifying naturally occurring substances that modify the effect of x-radiation on mammalian cells and discusses the role of physiologic substances in modifying radiation injuries on mammalian normal and tumor cells

Modification of the sensitivity and repair of potentially lethal damage by diethyldithiocarbamate during and following exposure of plateau-phase cultures of mammalian cells to radiation and cis-diamminedichloroplatinum(II)

International Nuclear Information System (INIS)

Evans, R.G.; Engel, C.; Wheatley, C.; Nielsen, J.

1982-01-01

Diethyldithiocarbamate (DDC), a chelating agent known to reduce levels of superoxide dismutase and glutathione peroxidase, appears to protect irradiated monolayers of mammalian cells when present for 1 hr before and during irradiation. To examine a possible cause of this modification, the repair of potentially lethal X-ray damage was examined with and without the presence of DDC in the medium overlying the cells postirradiation. Although little repair was seen in full medium alone when DDC was added to the full medium, the amount of repair was comparable to that seen under optimum repair conditions, that is, in Hanks' balanced salt solution. The t 1/2 of the repair process in Hanks' balanced salt solution or in full medium with DDC added was comparable and of the order of 1 to 1.5 hr. The cis-platinum sensitivity of the monolayers is significantly modified by the addition of DDC, and the nature of the modification is dependent upon the time at which the DDC is added to the cells following initiation of cis-platinum exposure. To investigate a possible reason for this protection by DDC, we examined the repair of potentially lethal cis-platinum damage in the cell monolayers. Minimal repair was noted in the presence of either Hanks' balanced salt solution or full medium, but when DDC was added to the full medium, the repair was tripled, and the t 1/2 of the repair process was approximately 2 hr. The ability of DDC to protect cells from exposure to both X-rays and cis-platinum, together with its augmentation of repair of potentially lethal damage following exposure to each, has broad clinical application and is being actively explored in tumor-bearing mice

Proceedings 3rd workshop on GRAPH inspection and traversal engineering : Grenoble, France, April 5, 2014

NARCIS (Netherlands)

Bosnacki, D.; Edelkamp, S.; Lluch Lafuente, A.; Wijs, A.J.

2014-01-01

These are the proceedings of the Third Workshop on GRAPH Inspection and Traversal Engineering (GRAPHITE 2014), which took place on April 5, 2014 in Grenoble, France, as a satellite event of the 17th European Joint Conferences on Theory and Practice of Software (ETAPS 2014). The aim of GRAPHITE is to

A promoter-level mammalian expression atlas

KAUST Repository

Forest, Alistair R R

2014-03-26

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

A promoter-level mammalian expression atlas

KAUST Repository

Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

2014-01-01

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

Specificity of chicken and mammalian transferrins in myogenesis

International Nuclear Information System (INIS)

Beach, R.L.; Popiela, Heinz; Festoff, B.W.

1985-01-01

Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

Traversible wormholes and the negative-stress-energy problem in the nonsymmetric gravitational theory

International Nuclear Information System (INIS)

Moffat, J.W.; Svoboda, T.

1991-01-01

The stress-energy tensor for a a general spherically symmetric matter distribution in the nonsymmetric gravitational theory (NGT) is determined using a heuristic argument. Using this tensor and the NGT field equations, it is shown that a wormhole threaded with matter must necessarily have a radial tension greater than the mass-energy density in the throat region. Hence, as in general relativity, a traversible wormhole in NGT must contain matter with a negative stress energy

Mammalian cell biology

International Nuclear Information System (INIS)

Elkind, M.M.

1979-01-01

This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

Brane surgery: energy conditions, traversable wormholes, and voids

International Nuclear Information System (INIS)

Barcelo, Carlos; Visser, Matt

2000-01-01

Branes are ubiquitous elements of any low-energy limit of string theory. We point out that negative tension branes violate all the standard energy conditions of the higher-dimensional spacetime they are embedded in; this opens the door to very peculiar solutions of the higher-dimensional Einstein equations. Building upon the (3+1)-dimensional implementation of fundamental string theory, we illustrate the possibilities by considering a toy model consisting of a (2+1)-dimensional brane propagating through our observable (3+1)-dimensional universe. Developing a notion of 'brane surgery', based on the Israel-Lanczos-Sen 'thin shell' formalism of general relativity, we analyze the dynamics and find traversable wormholes, closed baby universes, voids (holes in the spacetime manifold), and an evasion (not a violation) of both the singularity theorems and the positive mass theorem. These features appear generic to any brane model that permits negative tension branes: This includes the Randall-Sundrum models and their variants

An Arduino microcontroller based digitalization of a vertical traversing mechanism used for the analysis of jet flows

Science.gov (United States)

Rahman, S. M. Rakibur; Roshid, S. M. Al Mamun Or; Nishan, Ishtiaque Ahmed

2017-12-01

This paper deals with the design of a drive system of traversing mechanism used to position the pitot tube in desired position of the jet flow field. In this system a stepper motor is driven by a `dual H bridge' motor driver and programmed Arduino microcontroller. The stepper motor is made to move in precise steps to obtain desired movement of the traversing mechanism. The jet flow is characterized in three distinct zones - initial zone, transition zone and developed zone. Each zone can be divided into required number of segments based on variation of velocity. By assigning number of segments, step range and number of steps in each segment as inputs, it is possible to collect data in all the flow zones according to our programmed schedule. The system will allow taking a large number of readings automatically.

A Study of Parallels Between Antarctica South Pole Traverse Equipment and Lunar/Mars Surface Systems

Science.gov (United States)

Mueller, Robert P.; Hoffman, Stephen, J.; Thur, Paul

2010-01-01

The parallels between an actual Antarctica South Pole re-supply traverse conducted by the National Science Foundation (NSF) Office of Polar Programs in 2009 have been studied with respect to the latest mission architecture concepts being generated by the United States National Aeronautics and Space Administration (NASA) for lunar and Mars surface systems scenarios. The challenges faced by both endeavors are similar since they must both deliver equipment and supplies to support operations in an extreme environment with little margin for error in order to be successful. By carefully and closely monitoring the manifesting and operational support equipment lists which will enable this South Pole traverse, functional areas have been identified. The equipment required to support these functions will be listed with relevant properties such as mass, volume, spare parts and maintenance schedules. This equipment will be compared to space systems currently in use and projected to be required to support equivalent and parallel functions in Lunar and Mars missions in order to provide a level of realistic benchmarking. Space operations have historically required significant amounts of support equipment and tools to operate and maintain the space systems that are the primary focus of the mission. By gaining insight and expertise in Antarctic South Pole traverses, space missions can use the experience gained over the last half century of Antarctic operations in order to design for operations, maintenance, dual use, robustness and safety which will result in a more cost effective, user friendly, and lower risk surface system on the Moon and Mars. It is anticipated that the U.S Antarctic Program (USAP) will also realize benefits for this interaction with NASA in at least two areas: an understanding of how NASA plans and carries out its missions and possible improved efficiency through factors such as weight savings, alternative technologies, or modifications in training and

To spread or not to spread - chromatin modifications in response to DNA damage

DEFF Research Database (Denmark)

Altmeyer, M.; Lukas, J.

2013-01-01

Chromatin modifications in response to DNA damage are vital for genome integrity. Multiple proteins and pathways required to generate specialized chromatin domains around DNA lesions have been identified and the increasing amount of information calls for unifying concepts that would allow us...... to grasp the ever-increasing complexity. This review aims at contributing to this trend by focusing on feed-forward and feedback mechanisms, which in mammalian cells determine the extent of chromatin modifications after DNA damage. We highlight the emerging notion that the nodal points of these highly...... dynamic pathways operate in a rate-limiting mode, whose deregulation can disrupt physiological boundaries between damaged and undamaged chromatin, dictate repair pathway choice, and determine the fate of cells exposed to genotoxic stress....

Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke

Directory of Open Access Journals (Sweden)

Joseph C. Griffis

2017-01-01

Full Text Available Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

Traverse across the Nelspruit batholith and the geology of the excursion route between Sabie and Witbank

International Nuclear Information System (INIS)

Robb, L.J.; Anhaeusser, C.R.

1981-01-01

A geologic survey was done on the traverse across the Nelspruit batholith and the geology of the excursion route between Sabie and Witbank. Rubidium isotopes, strontium 86 and strontium 87 were used to determine the rock age. The petrogenetic aspects relating to the Nelspruit batholith were also studied

Representation and traversal of documentation space. Data analysis, neuron networks and image banks

International Nuclear Information System (INIS)

Lelu, A.; Rosenblatt, D.

1986-01-01

Improvements in the visual representation of considerable amounts of data for the user is necessary for progress in documentation systems. We review practical implementations in this area, which additionally integrate concepts arising from data analysis in the most general sense. The relationship between data analysis and neuron networks is then established. Following a description of simulation experiments, we finally present software for outputting and traversing image banks which integrate most of the concept developed in this article [fr

Mosaic evolution of the mammalian auditory periphery.

Science.gov (United States)

Manley, Geoffrey A

2013-01-01

The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

The use of recombinant DNA techniques to study radiation-induced damage, repair and genetic change in mammalian cells

International Nuclear Information System (INIS)

Thacker, J.

1986-01-01

A brief introduction is given to appropriate elements of recombinant DNA techniques and applications to problems in radiobiology are reviewed with illustrative detail. Examples are included of studies with both 254 nm ultraviolet light and ionizing radiation and the review progresses from the molecular analysis of DNA damage in vitro through to the nature of consequent cellular responses. The review is dealt with under the following headings: Molecular distribution of DNA damage, The use of DNA-mediated gene transfer to assess damage and repair, The DNA double strand break: use of restriction endonucleases to model radiation damage, Identification and cloning of DNA repair genes, Analysis of radiation-induced genetic change. (UK)

Behavior of a test gyroscope moving towards a rotating traversable wormhole

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Chandrachur [Department of Astronomy and Astrophysics, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400005 India (India); Pradhan, Parthapratim, E-mail: chandrachur.chakraborty@tifr.res.in, E-mail: pppradhan77@gmail.com [Department of Physics, Vivekananda Satabarshiki Mahavidyalaya, Manikpara, West Midnapur, 721513 India (India)

2017-03-01

The geodesic structure of the Teo wormhole is briefly discussed and some observables are derived that promise to be of use in detecting a rotating traversable wormhole indirectly, if it does exist. We also deduce the exact Lense-Thirring (LT) precession frequency of a test gyroscope moving toward a rotating traversable Teo wormhole. The precession frequency diverges on the ergoregion, a behavior intimately related to and governed by the geometry of the ergoregion, analogous to the situation in a Kerr spacetime. Interestingly, it turns out that here the LT precession is inversely proportional to the angular momentum ( a ) of the wormhole along the pole and around it in the strong gravity regime, a behavior contrasting with its direct variation with a in the case of other compact objects. In fact, divergence of LT precession inside the ergoregion can also be avoided if the gyro moves with a non-zero angular velocity in a certain range. As a result, the spin precession frequency of the gyro can be made finite throughout its whole path, even very close to the throat, during its travel to the wormhole. Furthermore, it is evident from our formulation that this spin precession not only arises due to curvature or rotation of the spacetime but also due to the non-zero angular velocity of the spin when it does not move along a geodesic in the strong gravity regime. If in the future, interstellar travel indeed becomes possible through a wormhole or at least in its vicinity, our results would prove useful in determining the behavior of a test gyroscope which is known to serve as a fundamental navigation device.

DNA synthesis in irradiated mammalian cells

International Nuclear Information System (INIS)

Painter, R.B.; California Univ., San Francisco; Young, B.R.

1987-01-01

One of the first responses observed in S phase mammalian cells that have suffered DNA damage is the inhibition of initiation of DNA replicons. In cells exposed to ionizing radiation, a single-strand break appears to be the stimulus for this effect, whereby the initiation of many adjacent replicons (a replicon cluster) is blocked by a single-strand break in any one of them. In cells exposed to ultraviolet light (u.v.), replicon initiation is blocked at fluences that induce about one pyrimidine dimer per replicon. The inhibition of replicon initiation by u.v. in Chinese hamster cells that are incapable of excising pyrimidine dimers from their DNA is virtually the same as in cells that are proficient in dimer excision. Therefore, a single-strand break formed during excision repair of pyrimidine dimers is not the stimulus for inhibition of replicon initiation in u.v.-irradiated cells. Considering this fact, as well as the comparative insensitivity of human ataxia telangiectasia cells to u.v.-induced inhibition of replicon initiation, we propose that a relatively rare lesion is the stimulus for u.v. -induced inhibition of replicon initiation. (author

A re-assessment of the safety of silver in household water treatment: rapid systematic review of mammalian in vivo genotoxicity studies.

Science.gov (United States)

Fewtrell, Lorna; Majuru, Batsirai; Hunter, Paul R

2017-06-20

Despite poor evidence of their effectiveness, colloidal silver and silver nanoparticles are increasingly being promoted for treating potentially contaminated drinking water in low income countries. Recently, however, concerns have been raised about the possible genotoxicity of particulate silver. The goal of this paper was to review the published mammalian in vivo genotoxicity studies using silver micro and nanoparticles. SCOPUS and Medline were searched using the following search string: ("DNA damage" OR genotox* OR Cytotox* OR Embryotox*) AND (silver OR AgNP). Included papers were any mammalian in vivo experimental studies investigating genotoxicity of silver particles. Studies were quality assessed using the ToxRTool. 16 relevant papers were identified. There were substantial variations in study design including the size of silver particles, animal species, target organs, silver dose, route of administration and the method used to detect genotoxicity. Thus, it was not possible to produce a definitive pooled result. Nevertheless, most studies showed evidence of genotoxicity unless using very low doses. We also identified one human study reporting evidence of "severe DNA damage" in silver jewellery workers occupationally exposed to silver particles. With the available evidence it is not possible to be definitive about risks to human health from oral exposure to silver particulates. However, the balance of evidence suggests that there should be concerns especially when considering the evidence from jewellery workers. There is an urgent need to determine whether people exposed to particulate silver as part of drinking water treatment have evidence of DNA damage.

Total K-vacancy production in Ne (10 MeV) traversing Al

International Nuclear Information System (INIS)

Groeneveld, K.O.; Kolb, B.; Schader, J.; Sevier, K.D.

1976-01-01

Deexcitation of projectile inner shell vacancies created while traversing a solid foil may take place via competing processes: a) vacancy sharing with foil atoms in close impacts, b) radiative and non-radiative electron capture, and c) such X-ray and Auger electron transitions are possible in the heavy ion projectile. The change in K-vacancy creation with foil thickness can be investigated by measuring either projectile or target X-rays where the vacancies are created by Coulomb excitation and process a. In the system Ne (10 MeV) on Al, detecting Al K X-rays, the Ne K-vacancy production probability has been determined. (orig.) [de

Static and dynamic traversable wormhole geometries satisfying the Ford-Roman constraints

International Nuclear Information System (INIS)

Kuhfittig, Peter K.F.

2002-01-01

It was shown by Ford and Roman in 1996 that quantum field theory severely constrains wormhole geometries on a macroscopic scale. The first part of this paper discusses a wide class of wormhole solutions that meet these constraints. The type of shape function used is essentially generic. The constraints are then discussed in conjunction with various redshift functions. Violations of the weak energy condition and traversability criteria are also considered. The second part of the paper analyzes analogous time-dependent (dynamic) wormholes with the aid of differential forms. It is shown that a violation of the weak energy condition is not likely to be avoidable even temporarily

Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step Förster resonance energy transfer imaging

Directory of Open Access Journals (Sweden)

Tongcheng Dai

2018-03-01

Full Text Available The blood–brain barrier (BBB and the blood–brain tumor barrier (BBTB prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma. KEY WORDS: Liposomes, Disks, Intact form, BBB, BBTB, FRET

Precession of a rapidly rotating cylinder flow: traverse through resonance

Science.gov (United States)

Lopez, Juan; Marques, Francisco

2014-11-01

The flow in a rapidly rotating cylinder that is titled and also rotating around another axis can undergo sudden transitions to turbulence. Experimental observations of this have been associated with triadic resonances. The experimental and theoretical results are well-established in the literature, but there remains a lack of understanding of the physical mechanisms at play in the sudden transition from laminar to turbulent flow with very small variations in the governing parameters. Here, we present direct numerical simulations of a traverse in parameter space through an isolated resonance, and describe in detail the bifurcations involved in the sudden transition. U.S. National Science Foundation Grant CBET-1336410 and Spanish Ministry of Education and Science Grant (with FEDER funds) FIS2013-40880.

Isolation of Lysosomes from Mammalian Tissues and Cultured Cells.

Science.gov (United States)

Aguado, Carmen; Pérez-Jiménez, Eva; Lahuerta, Marcos; Knecht, Erwin

2016-01-01

Lysosomes participate within the cells in the degradation of organelles, macromolecules, and a wide variety of substrates. In any study on specific roles of lysosomes, both under physiological and pathological conditions, it is advisable to include methods that allow their reproducible and reliable isolation. However, purification of lysosomes is a difficult task, particularly in the case of cultured cells. This is mainly because of the heterogeneity of these organelles, along with their low number and high fragility. Also, isolation methods, while disrupting plasma membranes, have to preserve the integrity of lysosomes, as the breakdown of their membranes releases enzymes that could damage all cell organelles, including themselves. The protocols described below have been routinely used in our laboratory for the specific isolation of lysosomes from rat liver, NIH/3T3, and other cultured cells, but can be adapted to other mammalian tissues or cell lines.

Comparing Geologic Data Sets Collected by Planetary Analog Traverses and by Standard Geologic Field Mapping: Desert Rats Data Analysis

Science.gov (United States)

Feng, Wanda; Evans, Cynthia; Gruener, John; Eppler, Dean

2014-01-01

Geologic mapping involves interpreting relationships between identifiable units and landforms to understand the formative history of a region. Traditional field techniques are used to accomplish this on Earth. Mapping proves more challenging for other planets, which are studied primarily by orbital remote sensing and, less frequently, by robotic and human surface exploration. Systematic comparative assessments of geologic maps created by traditional mapping versus photogeology together with data from planned traverses are limited. The objective of this project is to produce a geologic map from data collected on the Desert Research and Technology Studies (RATS) 2010 analog mission using Apollo-style traverses in conjunction with remote sensing data. This map is compared with a geologic map produced using standard field techniques.

Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

International Nuclear Information System (INIS)

Dudek, E.J.; Roth, R.M.

1990-01-01

Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs

Homogenization of Mammalian Cells.

Science.gov (United States)

de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

2015-11-02

Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

Evolutionary patterns of RNA-based duplication in non-mammalian chordates.

Directory of Open Access Journals (Sweden)

Ming Chen

Full Text Available The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young retrocopies in ancient chordate species. Upon comparing these non-mammalian chordate species to the mammalian species, we observed that a larger fraction of the non-mammalian retrocopies was under strong evolutionary constraints than mammalian retrocopies are, as evidenced by signals of purifying selection and expression profiles. For the Western clawed frog, Medaka, and Sea squirt, many retrogenes have evolved gonad and brain expression patterns, similar to what was observed in human. Testing of retrogene movement in the Medaka genome, where the nascent sex chrosomes have been well assembled, did not reveal any significant gene movement. Taken together, our analyses demonstrate that RNA-based duplication generates many functional genes and can make a significant contribution to the evolution of non-mammalian genomes.

78 FR 37966 - Safety Zone; National Cherry Festival Air Show and Fireworks Display, West Grand Traverse Bay...

Science.gov (United States)

2013-06-25

...-AA00 Safety Zone; National Cherry Festival Air Show and Fireworks Display, West Grand Traverse Bay... the hazards associated with fireworks displays and aircraft involved in the National Cherry Festival... Festival fireworks display and air show. At the close of the comment period, no comments were received in...

Mammalian diversity: gametes, embryos and reproduction.

Science.gov (United States)

Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

2006-01-01

The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

Science.gov (United States)

Jenkins, F A; Crompton, A W; Downs, W R

1983-12-16

Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

Role of paramagnetic chromium in chromium(VI)-induced damage in cultured mammalian cells.

OpenAIRE

Sugiyama, M

1994-01-01

Chromium(VI) compounds are known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to chromium(III), the formation of paramagnetic chromium such as chromium(V) and chromium(III) is believed to play a role in the adverse biological effects of chromium(VI) compounds. The present report, uses electron spin resonance (ESR) spectroscopy; the importance of the role of paramagnetic chromium in chromium(VI)-induced damage in intac...

Inhibition of polo-like kinase-1 by DNA damage occurs in an ATM- or ATR-dependent fashion

NARCIS (Netherlands)

van Vugt, MATM; Smits, VAJ; Klompmaker, R; Medema, RH

2001-01-01

Polo-like kinases play multiple roles in different phases of mitosis. We have recently shown that the mammalian polo-like kinase, Plk1, is inhibited in response to DNA damage and that this inhibition may lead to cell cycle arrests at multiple points in mitosis. Here we have investigated the role of

Alpha radiation-induced alterations of the proliferation kinetics, chromatin structure and gene expression in mammalian cells

International Nuclear Information System (INIS)

Hieber, L.

1983-01-01

Exponentially growing mammalian cells were exposed to 3.4 MeV alpha particles. The chromatin of cells arrested in G2 by alpha irradiation was severely damaged, though all cells were still capable to condensate their chromatin after fusion with mitotic cells. In addition to the common types of aberrations (breaks, gaps, dicentrics and exchanges) cells were found possessing one or more chromosomes with long stretches of undercondensed chromatin. Repair of these lesions was indicated by site specific unscheduled DNA synthesis and by the observation that condensation of these regions improved during G2 arrest. Furthermore, during G2 arrest the synthesis of two cellular proteins was stimulated. This was studied by two-dimensional gel electrophoresis of 35 S-methionine labeled cellular proteins. All these findings provided evidence that radiation-induced G2 arrest is caused by chromatin damage, which prevents regular chromosome condensation for mitosis. (orig./MG) [de

A stochastic DNA walker that traverses a microparticle surface

Science.gov (United States)

Jung, C.; Allen, P. B.; Ellington, A. D.

2016-02-01

Molecular machines have previously been designed that are propelled by DNAzymes, protein enzymes and strand displacement. These engineered machines typically move along precisely defined one- and two-dimensional tracks. Here, we report a DNA walker that uses hybridization to drive walking on DNA-coated microparticle surfaces. Through purely DNA:DNA hybridization reactions, the nanoscale movements of the walker can lead to the generation of a single-stranded product and the subsequent immobilization of fluorescent labels on the microparticle surface. This suggests that the system could be of use in analytical and diagnostic applications, similar to how strand exchange reactions in solution have been used for transducing and quantifying signals from isothermal molecular amplification assays. The walking behaviour is robust and the walker can take more than 30 continuous steps. The traversal of an unprogrammed, inhomogeneous surface is also due entirely to autonomous decisions made by the walker, behaviour analogous to amorphous chemical reaction network computations, which have been shown to lead to pattern formation.

Repair of sublethal damage in mammalian cells irradiated at ultrahigh dose rates

International Nuclear Information System (INIS)

Gerweck, L.E.; Epp, E.R.; Michaels, H.B.; Ling, C.C.; Peterson, E.C.

1979-01-01

The lethal response of asynchronous Chinese hamster ovary (CHO) cells exposed to single and split doses of radiation at conventional or ultrahigh dose rates has been examined to determine whether repair of sublethal damage occurs in cells irradiated at ultrahigh dose rates. The high-intensity irradiations were performed with electrons delivered in single 3-nsec pulses from a 600-kV field emission source under medium-removed, thin-layer conditions. Conventional dose-rate experiments were done under identical thin-layer conditions with 50-kVp x rays, or under full-medium conditions with 280-kVp x rays. Oxygenated cells were irradiated and maintained at 22 to 24 0 C between exposures. Survival did not increase as the time between two doses of pulsed electrons increased from 0 to 4 min, indicating no evidence of fast repair. However, increased survival was observed when 30 to 90 min was allowed to elapse between the split doses. The half-time for maximum repair was approx. = 30 min irrespective of the exposure conditions and radiation modality used. Observed repair ratios increased from approx. = 2 to 4 as the single-dose surviving fraction decreased from 10 -2 to 5 x 10 -4 . Over this survival range the repair ratios, measured at the same value of surviving fraction, were independent of dose rate. The observed repair ratios imply that the shoulder regions of the nonfractionated x-ray and pulsed-electron survival curves were not completely restored between the split doses. However, the fraction of the shoulder restored between split doses of radiation was dose-rate-independent. It is concluded that sublethal damage can be repaired in oxygenated CHO cells irradiated at dose rates of the order of 10 11 rad/sec

Track structure model for damage to mammalian cell cultures during solar proton events

Science.gov (United States)

Cucinotta, F. A.; Wilson, J. W.; Townsend, L. W.; Shinn, J. L.; Katz, R.

1992-01-01

Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.

Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

International Nuclear Information System (INIS)

Kamp, Hennicke G.; Eisenbrand, Gerhard; Schlatter, Josef; Wuerth, Kirsten; Janzowski, Christine

2005-01-01

Ochratoxin A (OTA) is a nephrotoxic/-carcinogenic mycotoxin, produced by several Aspergillus- and Penicillium-strains. Humans are exposed to OTA via food contamination, a causal relationship of OTA to human endemic Balkan nephropathy is still under debate. Since DNA-adducts of OTA or its metabolites could not be identified unambiguously, its carcinogenic effectiveness might be related to secondary effects, such as oxidative cell damage or cell proliferation. In this study, OTA mediated induction of (oxidative) DNA damage, cytotoxicity (necrosis, growth inhibition, apoptosis) and modulation of glutathione were investigated in cell lines (V79, CV-1) and primary rat kidney cells. After 24 h incubation, viability of V79 cells was strongly decreased by OTA concentrations >2.5 μmol/L, whereas CV-1 cells were clearly less sensitive. Strong growth inhibition occurred in both cell lines (IC 50 ∼2 μmol/L). Apoptosis, detected with an immunochemical test and with flow cytometry, was induced by >1 μmol/L OTA. Oxidative DNA damage, detected by comet assay after additional treatment with repair enzymes, was induced in all cell systems already at five-fold lower concentrations. Glutathione in CV-1 cells was depleted after 1 h incubation (>100 μmol/L). In contrast, an increase was measured after 24 h incubation (>0.5 μmol/L). In conclusion, OTA induces oxidative DNA damage at low, not yet cytotoxic concentrations. Oxidative DNA damage might initiate cell transformation eventually in connection with proliferative response following cytotoxic cell death. Both events might represent pivotal factors in the chain of cellular events leading into nephro-carcinogenicity of OTA

Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells.

Science.gov (United States)

Bru, Samuel; Samper-Martín, Bàrbara; Quandt, Eva; Hernández-Ortega, Sara; Martínez-Laínez, Joan M; Garí, Eloi; Rafel, Marta; Torres-Torronteras, Javier; Martí, Ramón; Ribeiro, Mariana P C; Jiménez, Javier; Clotet, Josep

2017-09-01

Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterizing Hypervelocity Impact (HVI-Induced Pitting Damage Using Active Guided Ultrasonic Waves: From Linear to Nonlinear

Directory of Open Access Journals (Sweden)

Menglong Liu

2017-05-01

Full Text Available Hypervelocity impact (HVI, ubiquitous in low Earth orbit with an impacting velocity in excess of 1 km/s, poses an immense threat to the safety of orbiting spacecraft. Upon penetration of the outer shielding layer of a typical two-layer shielding system, the shattered projectile, together with the jetted materials of the outer shielding material, subsequently impinge the inner shielding layer, to which pitting damage is introduced. The pitting damage includes numerous craters and cracks disorderedly scattered over a wide region. Targeting the quantitative evaluation of this sort of damage (multitudinous damage within a singular inspection region, a characterization strategy, associating linear with nonlinear features of guided ultrasonic waves, is developed. Linear-wise, changes in the signal features in the time domain (e.g., time-of-flight and energy dissipation are extracted, for detecting gross damage whose characteristic dimensions are comparable to the wavelength of the probing wave; nonlinear-wise, changes in the signal features in the frequency domain (e.g., second harmonic generation, which are proven to be more sensitive than their linear counterparts to small-scale damage, are explored to characterize HVI-induced pitting damage scattered in the inner layer. A numerical simulation, supplemented with experimental validation, quantitatively reveals the accumulation of nonlinearity of the guided waves when the waves traverse the pitting damage, based on which linear and nonlinear damage indices are proposed. A path-based rapid imaging algorithm, in conjunction with the use of the developed linear and nonlinear indices, is developed, whereby the HVI-induced pitting damage is characterized in images in terms of the probability of occurrence.

An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

Directory of Open Access Journals (Sweden)

Young-Geun Lee

2013-11-01

Full Text Available BackgroundMammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds.MethodsWe performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course.ResultsAmong the 68 cases of mammalian bite injury, 58 (85% were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap.ConclusionsBased on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds.

Detection of DNA strand breaks in mammalian cells using the radioresistant bacterium PprA protein

International Nuclear Information System (INIS)

Satoh, Katsuya; Wada, Seiichi; Narumi, Issay; Kikuchi, Masahiro; Funayama, Tomoo; Kobayashi, Yasuhiko

2003-01-01

We have previously found that the PprA protein from Deinococcus radiodurans possesses ability to recognize DNA carrying strand breaks. In the present study, we attempted to visualize radiation-induced DNA strand breaks with PprA protein using immunofluorescence technique to elucidate the DNA damage response mechanism in mammalian cultured cells. As a result, colocalization of Cy2 and DAPI fluorescent signals was observed. This observation suggests that DNA strand breaks in the nucleus of CHO-K1 cells were effectively detected using the PprA protein. The amount of DNA strand breaks (integrated density of Cy2 fluorescent signals) was increased with the increase in the radiation dose. (author)

Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems. Comprehensive report, 1 February 1981-15 September 1983

International Nuclear Information System (INIS)

Friedberg, E.C.

1983-01-01

We have explored the molecular mechanism of the repair of DNA at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian (including human) cells. We have demonstrated that uv endonuclease of phage T4 not only possesses pyrimidine dimer (PD)-DNA glycosylase activity but also apyrimidinic (AP) endonuclease activity. The demonstration of both activities provided an explanation for the specific endonucleosytic cleavage of DNA at sites of pyrimidine dimers catalyzed by this small protein. A new apurinic/apyrimidinic (AP) endonuclease, specific for sites of of base loss in single stranded DNA has been isolated from E. celi and presumably recognizes these lesions in single stranded regions of duplex DNA. We have partially purified this enzyme and have carried out a preliminary characterization of the activity. We treated xeroderma pigmentosum and normal cells with sodium butyrate in the hope of restoring normal levels of excision repair to the former. Although this result was not obtained, we established that all cells treated with sodium butyrate show enhanced levels of repair synthesis, thus providing a means for increasing the sensitivity of this commonly used technique for measuring DNA repair in mammalian cells in culture

Distinct radioprotective activities of major heat shock proteins in irradiated mammalian cells

International Nuclear Information System (INIS)

Kabakov, Alexander; Malyutina, Yana; Kudryavtsev, Vladimir

2008-01-01

Full text: Several years ago we have suggested that heat shock proteins (Hsps) can be involved in cellular and tissue mechanisms of protection from ionizing radiation. At present, the accumulated experimental data do allow us to characterize three major mammalian Hsps, Hsp70, Hsp27 and Hsp90, as specific endogenous radioprotectors which are able to prevent or minimize cell death resulting from the radiation exposure. It follows from the many findings that the radioprotective effect of these Hsps is particularly manifested in their ability to attenuate apoptosis in various normal and tumor cells irradiated in vivo or in vitro. The obtained data already enable to suggest three main mechanisms of the radioprotection conferred by the excess Hsps: 1) Modulation of the intracellular signaling so that the apoptotic signal transduction is blocked, whereas the 'cell survival' signal transduction is stimulated; 2) Suppression of the radiation-associated free radical generation and apoptosis induced by reactive oxygen species (ROS); 3) Attenuation of the genotoxic impact of ionizing radiation. The latter suggested mechanism seems particularly intriguing and implies that the excess Hsps can somehow contribute to protection/repair of genomic DNA from radiation-induced damage. According to our recent results, Hsp90 is indeed involved in the post-irradiation repair of nuclear DNA, while excess Hsp70 can beneficially affect the p53-mediated DNA damage response in irradiated cells to ensure their long-term survival and recovery. As for Hsp27, we found that its accumulation in target cells increases their radioresistance by enhancing the irradiation-responsive activation of anti apoptotic pathways. While the Hsp70 and Hsp27 seem to perform different functions in irradiated cells, the synergistic enhancement of radioprotection was clearly observed in the cells enriched by the both the Hsps. In vivo, such radioprotective activities of the major mammalian Hsps may play a role in

Surgical manipulation of mammalian embryos in vitro.

Science.gov (United States)

Naruse, I; Keino, H; Taniguchi, M

1997-04-01

Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

Application of CFD in Bioprocessing: Separation of mammalian cells using disc stack centrifuge during production of biotherapeutics.

Science.gov (United States)

Shekhawat, Lalita Kanwar; Sarkar, Jayati; Gupta, Rachit; Hadpe, Sandeep; Rathore, Anurag S

2018-02-10

Centrifugation continues to be one of the most commonly used unit operations for achieving efficient harvest of the product from the mammalian cell culture broth during production of therapeutic monoclonal antibodies (mAbs). Since the mammalian cells are known to be shear sensitive, optimal performance of the centrifuge requires a balance between productivity and shear. In this study, Computational Fluid Dynamics (CFD) has been successfully used as a tool to facilitate efficient optimization. Multiphase Eulerian-Eulerian model coupled with Gidaspow drag model along with Eulerian-Eulerian k-ε mixture turbulence model have been used to quantify the complex hydrodynamics of the centrifuge and thus evaluate the turbulent stresses generated by the centrifugal forces. An empirical model has been developed by statistical analysis of experimentally observed cell lysis data as a function of turbulent stresses. An operating window that offers the optimal balance between high productivity, high separation efficiency, and low cell damage has been identified by use of CFD modeling. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration

Directory of Open Access Journals (Sweden)

Yuval Rinkevich

2014-05-01

Full Text Available The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.

Compound Poisson Processes and Clustered Damage of Radiation Induced DNA Double Strand Breaks

International Nuclear Information System (INIS)

Gudowska-Nowak, E.; Ritter, S.; Taucher-Scholz, G.; Kraft, G.

2000-01-01

Recent experimental data have demonstrated that DNA damage induced by densely ionizing radiation in mammalian cells is distributed along the DNA molecule in the form of clusters. The principal constituent of DNA damage are double-strand breaks (DSB) which are formed when the breaks occur in both DNA strands and are directly opposite or separated by only a few base pairs. DSBs are believed to be most important lesions produced in chromosomes by radiation; interaction between DSBs can lead to cell killing, mutation or carcinogenesis. The paper discusses a model of clustered DSB formation viewed in terms of compound Poisson process along with the predictive essay of the formalism in application to experimental data. (author)

Manifestations of damage from ionizing radiation in mammalian cells in the postirradiation generations

International Nuclear Information System (INIS)

Hopwood, L.E.; Tolmach, L.J.

1979-01-01

The lethally irradiated cell does not immediately cease metabolism. It may undergo one or many divisions before physiological death and disintegration ensue. Attention has been focused mainly on cell behavior during the generation in which the radiation is delivered, and cell behavior is in several respects very different in the irradiated generation from what it is in the succeeding generations. In particular, some of the responses in the irradiated generation are transient, and certain responses seem unrelated to lethal damage. The behavior of lethally irradiated cells during the postirradiation generations before they die is intrinsically of interest, and should provide information concerning the nature of the lethal damage they harbor. Accordingly, in reviewing the behavior of irradiated cells, the discussion is confined for the most part, though not entirely, to the postirradiations, even though distinction between the irradiated and the postirradiation generations is in several respects arbitrary. Effects at the cellular level are considered first; the final part of this section is devoted to a discussion of in vivo measurements of cellular effects, and includes responses that are properly classified as effects at the tissue level. The effects at the subcellular level are considered; the discussion is restricted to chromosomal effects. Biochemical effects are then considered; these are concerned entirely with macromolecular synthesis. In the final section possible interpretations of the experimental findings in terms of cell lethality are discussed but not loss of colony-forming ability (''clonogenicity'') directly

Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages.

Science.gov (United States)

Jinadasa, Rasika N; Bloom, Stephen E; Weiss, Robert S; Duhamel, Gerald E

2011-07-01

Cytolethal distending toxin (CDT) is a heterotrimeric AB-type genotoxin produced by several clinically important Gram-negative mucocutaneous bacterial pathogens. Irrespective of the bacterial species of origin, CDT causes characteristic and irreversible cell cycle arrest and apoptosis in a broad range of cultured mammalian cell lineages. The active subunit CdtB has structural homology with the phosphodiesterase family of enzymes including mammalian DNase I, and alone is necessary and sufficient to account for cellular toxicity. Indeed, mammalian cells treated with CDT initiate a DNA damage response similar to that elicited by ionizing radiation-induced DNA double strand breaks resulting in cell cycle arrest and apoptosis. The mechanism of CDT-induced apoptosis remains incompletely understood, but appears to involve both p53-dependent and -independent pathways. While epithelial, endothelial and fibroblast cell lines respond to CDT by undergoing arrest of cell cycle progression resulting in nuclear and cytoplasmic distension that precedes apoptotic cell death, cells of haematopoietic origin display rapid apoptosis following a brief period of cell cycle arrest. In this review, the ecology of pathogens producing CDT, the molecular biology of bacterial CDT and the molecular mechanisms of CDT-induced cytotoxicity are critically appraised. Understanding the contribution of a broadly conserved bacterial genotoxin that blocks progression of the mammalian cell cycle, ultimately causing cell death, should assist with elucidating disease mechanisms for these important pathogens.

Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

Science.gov (United States)

Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

2016-12-15

Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

Science.gov (United States)

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-31

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

Science.gov (United States)

Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

2015-01-01

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

Elucidating the Role of Injury-Induced Electric Fields (EFs in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

Directory of Open Access Journals (Sweden)

Matthew L Baer

Full Text Available Injury to the vertebrate central nervous system (CNS induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

Rheotaxis guides mammalian sperm

Science.gov (United States)

Miki, Kiyoshi; Clapham, David E

2013-01-01

Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

MARCH-1987

Indian Academy of Sciences (India)

How does cobalamin (vitamin B12) enter and traverse mammalian cells? ... Coimmobilization of D-amino acid oxidase and catalase by entrapment of Trigonopis .... in membrane system II: can a neutral glycolipid function as lectin receptor in

Building the mammalian testis

DEFF Research Database (Denmark)

Svingen, Terje; Koopman, Peter

2013-01-01

Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial...

Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

Science.gov (United States)

2015-11-04

Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

DNA repair in non-mammalian animals

International Nuclear Information System (INIS)

Mitani, Hiroshi

1984-01-01

Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

Incorporation of mammalian actin into microfilaments in plant cell nucleus

Directory of Open Access Journals (Sweden)

Paves Heiti

2004-04-01

Full Text Available Abstract Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area.

Amino acids in the cultivation of mammalian cells.

Science.gov (United States)

Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

2016-05-01

Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52

International Nuclear Information System (INIS)

Veelen, Lieneke R. van; Essers, Jeroen; Rakt, Mandy W.M.M. van de; Odijk, Hanny; Pastink, Albert; Zdzienicka, MaIgorzata Z.; Paulusma, Coen C.; Kanaar, Roland

2005-01-01

Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response

Plasma treatment of mammalian vascular cells : A quantitative description

NARCIS (Netherlands)

Kieft, IE; Darios, D; Roks, AJM; Stoffels, E

For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

Plasma treatment of mammalian vascular cells: a quantitative description

NARCIS (Netherlands)

Kieft, I.E.; Darios, D.; Roks, A.J.M.; Stoffels - Adamowicz, E.

2005-01-01

For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

OpenAIRE

Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N.; Lee, Seung-Rock

2014-01-01

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells ...

Binucleate cell formation correlates to loss of colony-forming ability in X-irradiated cultured mammalian cells

International Nuclear Information System (INIS)

Sasaki, H.; Yoshinaga, H.; Kura, S.

1986-01-01

The relationship between binucleate cell formation and the loss of colony-forming ability was examined in several cultured mammalian cell lines irradiated with X rays. The maximum fraction of binucleate cells after X irradiation increased dose-dependently within the range in which reproductive cell death might predominate over interphase cell death. When the logarithm of percentage survival was plotted against the percentage binucleate cells, a similar correlation was found for all cell lines tested, with the exception of mouse leukemia L5178Y cells, the most radiosensitive cells used. These observations suggest that the fraction of binucleate cells in the cell population can serve as a measure of cellular radiation damage

Fundamental aspects of the freezing of cells, with emphasis on mammalian ova and embryos

Energy Technology Data Exchange (ETDEWEB)

Mazur, P.

1980-01-01

The problem in cryobiology is how to cool cells to -196/sup 0/C and return them to normal temperatures without killing them. One important factor is the presence of a protective additive like glycerol or dimethyl sulfoxide. Mammalian cells rarely survive freezing to below -40/sup 0/C in its absence. In the presence of an additive, survival is critically dependent on the cooling rate. Supraoptimal rates and suboptimal rates are both damaging. Death at supraoptimal rates is the result of the formation of intracellular ice and its recrystallization during warming. Death at suboptimal rates is a consequence of the major alterations in aqueous solutions produced by ice formation. The chief effects are a major reduction in the fraction of the solution remaining unfrozen at a given temperature and a major increase in the solute concentration of that fraction. The introduction of molar concentrations of additive greatly reduces both the fraction frozen and the concentration of electrolytes in the unfrozen channels and in the cell interior. Usually, freezing either kills cells outright or it results in survivors that retain full capacity to function. But there is the possibility that in some cases survivors may in fact be impaired genetically or physiologically. All evidence indicates that genetic damage does not occur. But there are clear examples in which freezing does induce nonlethal physiological damage. (ERB)

Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation

International Nuclear Information System (INIS)

Tokuyama, Yuka; Terato, Hiroaki; Furusawa, Yoshiya; Ide, Hiroshi; Yasui, Akira

2015-01-01

Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV µm -1 , respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process. (author)

Bystander effects: intercellular transmission of radiation damage signals

Energy Technology Data Exchange (ETDEWEB)

Little, J.B.; Azzam, E.I.; Toledo, S.M. de; Nagasawa, H

2002-07-01

Biological effects were examined in confluent cultures of fibroblasts and epithelial cells exposed to very low mean doses of alpha radiation, doses by which only 1-2% of the cells were actually traversed by an alpha particle. Enhanced frequencies of sister chromatid exchanges and HPRT mutations occurred in the non-irradiation, 'bystander' cells associated with a similar increase in the frequency of micronuclei, indicating the induction of DNA damage in these cells. In order to gain information concerning molecular pathways, changes in gene expression were examined in bystander cells by western analysis and in situ immunofluorescence staining. The expression levels of p53, p21 and MDM2 were significantly modulated in bystander cells: the damage signals leading to these changes were transmitted from irradiated to bystander cells by gap junction mediated intracellular communication. The bystander response was suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, suggesting the effect may be mediated by oxidative stress. To examine other signalling pathways responsive to oxidative stress, the activation of stress-related kinases and their downstream transcription factors were analysed in bystander cells by western blotting and electrophoretic mobility shift assays: a 2-4 fold increase in the phosphorylation levels of JNK, EPK1/2, p90RSK, Elk-1 and ATF2 was observed. These changes were detected by 15 min after irradiation and persisted for at least 1 h. These findings indicate the activation of multiple signal transduction pathways in bystander cells, involving signals arising from the plasma membrane as well as from DNA damage. (author)

Next-generation mammalian genetics toward organism-level systems biology.

Science.gov (United States)

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

DNA damage caused by ionizing radiation

International Nuclear Information System (INIS)

Sachs, R.K.; Peili Chen; Hahnfeldt, P.J.; Klatky, L.R.

1992-01-01

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions. 51 refs., 5 figs

Dynamic modeling and mobility analysis of the transforming roving-rolling explorer (TRREx) as it Traverses Rugged Martian Terrain

Science.gov (United States)

Edwin, Lionel E.; Mazzoleni, Andre P.

2016-03-01

All planetary surface exploration missions thus far have employed traditional rovers with a rocker-bogie suspension. These rovers can navigate moderately rough and flat terrain, but are not designed to traverse rugged terrain with steep slopes. The fact is, however, that the most scientifically interesting missions require exploration platforms with capabilities for navigating such types of rugged terrain. This issue motivates the development of new kinds of rovers that take advantage of the latest advances in robotic technologies to traverse rugged terrain efficiently. This work analyzes one such rover concept called the Transforming Roving-Rolling Explorer (TRREx) that is principally aimed at addressing the above issue. Biologically inspired by the way the armadillo curls up into a ball when threatened, and the way the golden wheel spider uses the dynamic advantages of a sphere to roll down hills when escaping danger, the TRREx rover can traverse like a traditional 6-wheeled rover over conventional terrain, but can also transform itself into a sphere, when necessary, to travel down steep inclines, or navigate rough terrain. This paper investigates the mobility of the TRREx when it is in its rolling mode, i.e. when it is a sphere and can steer itself through actuations that shift its center of mass to achieve the desired direction of roll. A mathematical model describing the dynamics of the rover in this spherical configuration is presented, and actuated rolling is demonstrated through computer simulation. Parametric analyzes that investigate the rover's mobility as a function of its design parameters are also presented. This work highlights the contribution of the spherical rolling mode to the enhanced mobility of the TRREx rover and how it could enable challenging surface exploration missions in the future.

Mammalian DNA Repair. Final Report

Energy Technology Data Exchange (ETDEWEB)

Wood, Richard D.

2003-01-24

The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

The preliminary study on the inductory signal triggering the error-prone DNA repair function in mammalian cells

International Nuclear Information System (INIS)

Su Zaozhong; Luo Zuyu

1989-01-01

The nature of the signal triggering error-prone DNA repair function in mammalian cells was studied from two notions: (1) Does the inducing signal result from the direct hitting the cellular targets by DNA-damaging agents? (2) Is inhibition of DNA replication a prerequisite condition for the triggering effect? Thus, the ultraviolet (UV)-irradiated exogenous DNAs were introduced into human and rat cells by transfection. The results showed that this transfection was able to induce the error-prone repair as efficient as direct UV-irradiation to cells. Moreover, the two inductory treaetments expressed similar kinetics and dose-responses. No matter whether the introduced DNAs initiated replication, they exhibited the incuctory activity. Therefore, it can be considered that DNA lesions itself, not the direct interaction of DNA-damaging agents with specific cellular targets, serve as a triggering signal for the inductory process. Inhibition of DNA replication is not a prerequisite for the inductory signal

Genomic footprinting in mammalian cells with ultraviolet light

International Nuclear Information System (INIS)

Becker, M.M.; Wang, Z.; Grossmann, G.; Becherer, K.A.

1989-01-01

A simple and accurate genomic primer extension method has been developed to detect ultraviolet footprinting patterns of regulatory protein-DNA interactions in mammalian genomic DNA. The technique can also detect footprinting or sequencing patterns introduced into genomic DNA by other methods. Purified genomic DNA, containing either damaged bases or strand breaks introduced by footprinting or sequencing reactions, is first cut with a convenient restriction enzyme to reduce its molecular weight. A highly radioactive single-stranded DNA primer that is complementary to a region of genomic DNA whose sequence or footprint one wishes to examine is then mixed with 50 micrograms of restriction enzyme-cut genomic DNA. The primer is approximately 100 bases long and contains 85 radioactive phosphates, each of specific activity 3000 Ci/mmol (1 Ci = 37 GBq). A simple and fast method for preparing such primers is described. Following brief heat denaturation at 100 degrees C, the solution of genomic DNA and primer is cooled to 74 degrees C and a second solution containing Taq polymerase (Thermus aquaticus DNA polymerase) and the four deoxynucleotide triphosphates is added to initiate primer extension of genomic DNA. Taq polymerase extends genomic hybridized primer until its polymerization reaction is terminated either by a damaged base or strand break in genomic DNA or by the addition of dideoxynucleotide triphosphates in the polymerization reaction. The concurrent primer hybridization-extension reaction is terminated after 5 hr and unhybridized primer is digested away by mung bean nuclease. Primer-extended genomic DNA is then denatured and electrophoresed on a polyacrylamide sequencing gel, and radioactive primer extension products are revealed by autoradiography

Mammalian Synthetic Biology: Engineering Biological Systems.

Science.gov (United States)

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

Science.gov (United States)

Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

2016-09-11

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Thicker three-dimensional tissue from a “symbiotic recycling system” combining mammalian cells and algae

Science.gov (United States)

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-01

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro “symbiotic recycling system” composed of mammalian cells and algae. PMID:28139713

Acoustophoretic Synchronization of Mammalian Cells in Microchannels

DEFF Research Database (Denmark)

Thévoz, P.; Adams, J.D.; Shea, H.

2010-01-01

We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel to selec......We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel...

Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

Science.gov (United States)

Mortusewicz, Oliver; Roth, Wera; Li, Na; Cardoso, M. Cristina; Meisterernst, Michael; Leonhardt, Heinrich

2008-01-01

The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair. PMID:19047459

The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.

Directory of Open Access Journals (Sweden)

Jan Karlseder

2004-08-01

Full Text Available The telomeric protein TRF2 is required to prevent mammalian telomeres from activating DNA damage checkpoints. Here we show that overexpression of TRF2 affects the response of the ATM kinase to DNA damage. Overexpression of TRF2 abrogated the cell cycle arrest after ionizing radiation and diminished several other readouts of the DNA damage response, including phosphorylation of Nbs1, induction of p53, and upregulation of p53 targets. TRF2 inhibited autophosphorylation of ATM on S1981, an early step in the activation of this kinase. A region of ATM containing S1981 was found to directly interact with TRF2 in vitro, and ATM immunoprecipitates contained TRF2. We propose that TRF2 has the ability to inhibit ATM activation at telomeres. Because TRF2 is abundant at chromosome ends but not elsewhere in the nucleus, this mechanism of checkpoint control could specifically block a DNA damage response at telomeres without affecting the surveillance of chromosome internal damage.

Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance.

Science.gov (United States)

Gibson, Shannon L; Narayanan, Latha; Hegan, Denise Campisi; Buermeyer, Andrew B; Liskay, R Michael; Glazer, Peter M

2006-12-08

Inherited defects in genes associated with DNA mismatch repair (MMR) have been linked to familial colorectal cancer. Cells deficient in MMR are genetically unstable and demonstrate a tolerance phenotype in response to certain classes of DNA damage. Some sporadic human cancers also show abnormalities in MMR gene function, typically due to diminished expression of one of the MutL homologs, MLH1. Here, we report that overexpression of the MutL homolog, human PMS2, can also cause a disruption of the MMR pathway in mammalian cells, resulting in hypermutability and DNA damage tolerance. A mouse fibroblast cell line carrying a recoverable lambda phage shuttle vector for mutation detection was transfected with either a vector designed to express hPMS2 or with an empty vector control. Cells overexpressing hPMS2 were found to have elevated spontaneous mutation frequencies at the cII reporter gene locus. They also showed an increase in the level of mutations induced by the alkylating agent, methynitrosourea (MNU). Clonogenic survival assays demonstrated increased survival of the PMS2-overexpressing cells following exposure to MNU, consistent with the induction of a damage tolerance phenotype. Similar results were seen in cells expressing a mutant PMS2 gene, containing a premature stop codon at position 134 and representing a variant found in an individual with familial colon cancer. These results show that dysregulation of PMS2 gene expression can disrupt MMR function in mammalian cells and establish an additional carcinogenic mechanism by which cells can develop genetic instability and acquire resistance to cytotoxic cancer therapies.

Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

Science.gov (United States)

Rebollo, Rita; Mager, Dixie L

2016-01-01

Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

Effects of Majorana physics on the UHE ν{sub τ} flux traversing the Earth

Energy Technology Data Exchange (ETDEWEB)

Duarte, Lucia [Universidad de la Republica, Instituto de Fisica, Facultad de Ingenieria, Montevideo (Uruguay); Romero, Ismael; Zapata, Gabriel; Sampayo, Oscar A. [Universidad Nacional de Mar del Plata, Instituto de Investigaciones Fisicas de Mar del Plata (IFIMAR), CONICET, UNMDP, Departamento de Fisica, Mar del Plata (Argentina)

2017-02-15

We study the effects produced by sterile Majorana neutrinos on the ν{sub τ} flux traversing the Earth, considering the interaction between the Majorana neutrinos and the standard matter as modeled by an effective theory. The surviving tau-neutrino flux is calculated using transport equations including Majorana neutrino production and decay. We compare our results with the pure Standard Model interactions, computing the surviving flux for different values of the effective lagrangian couplings, considering the detected flux by IceCube for an operation time of 10 years, and Majorana neutrinos with mass m{sub N} ∝ m{sub τ}. (orig.)

Is ultraviolet enhanced reactivation of mammalian virus mutagenic

International Nuclear Information System (INIS)

Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

1981-01-01

Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

Biological effectiveness of high-energy protons - Target fragmentation

International Nuclear Information System (INIS)

Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Shinn, J.; Hajnal, F.

1991-01-01

High-energy protons traversing tissue produce local sources of high-linear-energy-transfer ions through nuclear fragmentation. The contribution of these target fragments to the biological effectiveness of high-energy protons using the cellular track model is examined. The effects of secondary ions are treated in terms of the production collision density using energy-dependent parameters from a high-energy fragmentation model. Calculations for mammalian cell cultures show that at high dose, at which intertrack effects become important, protons deliver damage similar to that produced by gamma rays, and with fragmentation the relative biological effectiveness (RBE) of protons increases moderately from unity. At low dose, where sublethal damage is unimportant, the contribution from target fragments dominates, causing the proton effectiveness to be very different from that of gamma rays with a strongly fluence-dependent RBE. At high energies, the nuclear fragmentation cross sections become independent of energy. This leads to a plateau in the proton single-particle-action cross section, below 1 keV/micron, since the target fragments dominate. 29 refs

A mammalianized synthetic nitroreductase gene for high-level expression

International Nuclear Information System (INIS)

Grohmann, Maik; Paulmann, Nils; Fleischhauer, Sebastian; Vowinckel, Jakob; Priller, Josef; Walther, Diego J

2009-01-01

The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy. We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays. In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect. Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans

Distributional congruence of mammalian herbivores in the Trans-Himalayan Mountains

NARCIS (Netherlands)

Namgail, T.; Wieren, van S.E.; Prins, H.H.T.

2013-01-01

Large-scale distribution and diversity patterns of mammalian herbivores, especially less charismatic species in alpine environments remain little understood. We studied distributional congruence of mammalian herbivores in the Trans-Himalayan region of Ladakh to see if the distributions of less

The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly

Science.gov (United States)

Riolobos, Laura; Domínguez, Carlos; Kann, Michael; Almendral, José M.

2015-01-01

It is unknown whether the mammalian cell cycle could impact the assembly of viruses maturing in the nucleus. We addressed this question using MVM, a reference member of the icosahedral ssDNA nuclear parvoviruses, which requires cell proliferation to infect by mechanisms partly understood. Constitutively expressed MVM capsid subunits (VPs) accumulated in the cytoplasm of mouse and human fibroblasts synchronized at G0, G1, and G1/S transition. Upon arrest release, VPs translocated to the nucleus as cells entered S phase, at efficiencies relying on cell origin and arrest method, and immediately assembled into capsids. In synchronously infected cells, the consecutive virus life cycle steps (gene expression, proteins nuclear translocation, capsid assembly, genome replication and encapsidation) proceeded tightly coupled to cell cycle progression from G0/G1 through S into G2 phase. However, a DNA synthesis stress caused by thymidine irreversibly disrupted virus life cycle, as VPs became increasingly retained in the cytoplasm hours post-stress, forming empty capsids in mouse fibroblasts, thereby impairing encapsidation of the nuclear viral DNA replicative intermediates. Synchronously infected cells subjected to density-arrest signals while traversing early S phase also blocked VPs transport, resulting in a similar misplaced cytoplasmic capsid assembly in mouse fibroblasts. In contrast, thymidine and density arrest signals deregulating virus assembly neither perturbed nuclear translocation of the NS1 protein nor viral genome replication occurring under S/G2 cycle arrest. An underlying mechanism of cell cycle control was identified in the nuclear translocation of phosphorylated VPs trimeric assembly intermediates, which accessed a non-conserved route distinct from the importin α2/β1 and transportin pathways. The exquisite cell cycle-dependence of parvovirus nuclear capsid assembly conforms a novel paradigm of time and functional coupling between cellular and virus life

Base Composition Characteristics of Mammalian miRNAs

Directory of Open Access Journals (Sweden)

Bin Wang

2013-01-01

Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

Science.gov (United States)

Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

2018-04-01

Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantum tunneling time of a Bose-Einstein condensate traversing through a laser-induced potential barrier

International Nuclear Information System (INIS)

Duan Zhenglu; Fan Bixuan; Yuan Chunhua; Zhang Weiping; Cheng Jing; Zhu Shiyao

2010-01-01

We theoretically study the effect of atomic nonlinearity on the tunneling time in the case of an atomic Bose-Einstein condensate (BEC) traversing the laser-induced potential barrier. The atomic nonlinearity is controlled to appear only in the region of the barrier by employing the Feshbach resonance technique to tune interatomic interaction in the tunneling process. Numerical simulation shows that the atomic nonlinear effect dramatically changes the tunneling behavior of the BEC matter wave packet and results in the violation of the Hartman effect and the occurrence of negative tunneling time.

Excitation of hybridized Dirac plasmon polaritons and transition radiation in multi-layer graphene traversed by a fast charged particle

Science.gov (United States)

Akbari, Kamran; Mišković, Zoran L.; Segui, Silvina; Gervasoni, Juana L.; Arista, Néstor R.

2018-06-01

We analyze the energy loss channels for a fast charged particle traversing a multi-layer graphene (MLG) structure with N layers under normal incidence. Focusing on a terahertz (THz) range of frequencies, and assuming equally doped graphene layers with a large enough separation d between them to neglect interlayer electron hopping, we use the Drude model for two-dimensional conductivity of each layer to describe hybridization of graphene’s Dirac plasmon polaritons (DPPs). Performing a layer decomposition of ohmic energy losses, which include excitation of hybridized DPPs (HDPPs), we have found for N = 3 that the middle HDPP eigenfrequency is not excited in the middle layer due to symmetry constraint, whereas the excitation of the lowest HDPP eigenfrequency produces a Fano resonance in the graphene layer that is first traversed by the charged particle. While the angular distribution of transition radiation emitted in the far field region also shows asymmetry with respect to the traversal order by the incident charged particle at supra-THz frequencies, the integrated radiative energy loss is surprisingly independent of both d and N for N ≤ 5, which is explained by a dominant role of the outer graphene layers in transition radiation. We have further found that the integrated ohmic energy loss in optically thin MLG scales as ∝1/N at sub-THz frequencies, which is explained by exposing the role of dissipative processes in graphene at low frequencies. Finally, prominent peaks are observed at supra-THz frequencies in the integrated ohmic energy loss for MLG structures that are not optically thin. The magnitude of those peaks is found to scale with N for N ≥ 2, while their shape and position replicate the peak in a double-layer graphene (N = 2), which is explained by arguing that plasmon hybridization in such MLG structures is dominated by electromagnetic interaction between the nearest-neighbor graphene layers.

ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

Science.gov (United States)

Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

2017-10-05

Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

Science.gov (United States)

Smith, Michael E; Monroe, J David

2016-01-01

Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

Dynamic Rocker-Bogie: Kinematical Analysis in a High-Speed Traversal Stability Enhancement

Directory of Open Access Journals (Sweden)

Sunxin Wang

2016-01-01

Full Text Available The rocker-bogie suspension system has robust capabilities to deal with uneven terrain because of its distributing of the payload over its six wheels uniformly, while there is one major shortcoming to high-speed traversal over the planar terrain. This paper proposes a new dynamic rocker-bogie suspension system with two modes of operation: it can expand the span of the rocker-bogie support polygon to increase travel rate when the terrain is planar; and it can switch to its original configuration to move by low speed when it is faced with rough terrain. The analysis on dynamic stability margin and kinematical simulation on the two operating modes of rocker-bogie are employed to analyze and verify the rationality and effectiveness of the modification in the structure.

Beyond xeroderma pigmentosum: DNA damage and repair in an ecological context. A tribute to James E. Cleaver.

Science.gov (United States)

Karentz, Deneb

2015-01-01

The ability to repair DNA is a ubiquitous characteristic of life on Earth and all organisms possess similar mechanisms for dealing with DNA damage, an indication of a very early evolutionary origin for repair processes. James E. Cleaver's career (initiated in the early 1960s) has been devoted to the study of mammalian ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of xeroderma pigmentosum and other human diseases caused by defects in DNA damage recognition and repair. This work by Jim and others has influenced the study of DNA damage and repair in a variety of taxa. Today, the field of DNA repair is enhancing our understanding of not only how to treat and prevent human disease, but is providing insights on the evolutionary history of life on Earth and how natural populations are coping with UVR-induced DNA damage from anthropogenic changes in the environment such as ozone depletion. © 2014 The American Society of Photobiology.

Apoptosis-like yeast cell death in response to DNA damage and replication defects

Energy Technology Data Exchange (ETDEWEB)

Burhans, William C.; Weinberger, Martin; Marchetti, Maria A.; Ramachandran, Lakshmi; D' Urso, Gennaro; Huberman, Joel A

2003-11-27

In budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe) yeast and other unicellular organisms, DNA damage and other stimuli can induce cell death resembling apoptosis in metazoans, including the activation of a recently discovered caspase-like molecule in budding yeast. Induction of apoptotic-like cell death in yeasts requires homologues of cell cycle checkpoint proteins that are often required for apoptosis in metazoan cells. Here, we summarize these findings and our unpublished results which show that an important component of metazoan apoptosis recently detected in budding yeast - reactive oxygen species (ROS) - can also be detected in fission yeast undergoing an apoptotic-like cell death. ROS were detected in fission and budding yeast cells bearing conditional mutations in genes encoding DNA replication initiation proteins and in fission yeast cells with mutations that deregulate cyclin-dependent kinases (CDKs). These mutations may cause DNA damage by permitting entry of cells into S phase with a reduced number of replication forks and/or passage through mitosis with incompletely replicated chromosomes. This may be relevant to the frequent requirement for elevated CDK activity in mammalian apoptosis, and to the recent discovery that the initiation protein Cdc6 is destroyed during apoptosis in mammals and in budding yeast cells exposed to lethal levels of DNA damage. Our data indicate that connections between apoptosis-like cell death and DNA replication or CDK activity are complex. Some apoptosis-like pathways require checkpoint proteins, others are inhibited by them, and others are independent of them. This complexity resembles that of apoptotic pathways in mammalian cells, which are frequently deregulated in cancer. The greater genetic tractability of yeasts should help to delineate these complex pathways and their relationships to cancer and to the effects of apoptosis-inducing drugs that inhibit DNA replication.

Apoptosis-like yeast cell death in response to DNA damage and replication defects

International Nuclear Information System (INIS)

Burhans, William C.; Weinberger, Martin; Marchetti, Maria A.; Ramachandran, Lakshmi; D'Urso, Gennaro; Huberman, Joel A.

2003-01-01

In budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe) yeast and other unicellular organisms, DNA damage and other stimuli can induce cell death resembling apoptosis in metazoans, including the activation of a recently discovered caspase-like molecule in budding yeast. Induction of apoptotic-like cell death in yeasts requires homologues of cell cycle checkpoint proteins that are often required for apoptosis in metazoan cells. Here, we summarize these findings and our unpublished results which show that an important component of metazoan apoptosis recently detected in budding yeast - reactive oxygen species (ROS) - can also be detected in fission yeast undergoing an apoptotic-like cell death. ROS were detected in fission and budding yeast cells bearing conditional mutations in genes encoding DNA replication initiation proteins and in fission yeast cells with mutations that deregulate cyclin-dependent kinases (CDKs). These mutations may cause DNA damage by permitting entry of cells into S phase with a reduced number of replication forks and/or passage through mitosis with incompletely replicated chromosomes. This may be relevant to the frequent requirement for elevated CDK activity in mammalian apoptosis, and to the recent discovery that the initiation protein Cdc6 is destroyed during apoptosis in mammals and in budding yeast cells exposed to lethal levels of DNA damage. Our data indicate that connections between apoptosis-like cell death and DNA replication or CDK activity are complex. Some apoptosis-like pathways require checkpoint proteins, others are inhibited by them, and others are independent of them. This complexity resembles that of apoptotic pathways in mammalian cells, which are frequently deregulated in cancer. The greater genetic tractability of yeasts should help to delineate these complex pathways and their relationships to cancer and to the effects of apoptosis-inducing drugs that inhibit DNA replication

Biological studies using mammalian cell lines and the current status of the microbeam irradiation system, SPICE

Energy Technology Data Exchange (ETDEWEB)

Konishi, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: tkonishi@nirs.go.jp; Ishikawa, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Iso, H. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Yasuda, N.; Oikawa, M. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Higuchi, Y. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Kato, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshimaku, Tokyo 171-8501 (Japan); Hafer, K. [Department of Radiation Oncology, UCLA School of Medicine, Los Angeles, CA (United States); Kodama, K. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Hamano, T.; Suya, N.; Imaseki, H. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2009-06-15

The development of SPICE (single-particle irradiation system to cell), a microbeam irradiation system, has been completed at the National Institute of Radiological Sciences (NIRS). The beam size has been improved to approximately 5 {mu}m in diameter, and the cell targeting system can irradiate up to 400-500 cells per minute. Two cell dishes have been specially designed: one a Si{sub 3}N{sub 4} plate (2.5 mm x 2.5 mm area with 1 {mu}m thickness) supported by a 7.5 mm x 7.5 mm frame of 200 {mu}m thickness, and the other a Mylar film stretched by pressing with a metal ring. Both dish types may be placed on a voice coil stage equipped on the cell targeting system, which includes a fluorescent microscope and a CCD camera for capturing cell images. This microscope system captures images of dyed cell nuclei, computes the location coordinates of individual cells, and synchronizes this with the voice coil motor stage and single-particle irradiation system consisting of a scintillation counter and a beam deflector. Irradiation of selected cells with a programmable number of protons is now automatable. We employed the simultaneous detection method for visualizing the position of mammalian cells and proton traversal through CR-39 to determine whether the targeted cells are actually irradiated. An immuno-assay was also performed against {gamma}-H2AX, to confirm the induction of DNA double-strand breaks in the target cells.

The shape of mammalian phylogeny

DEFF Research Database (Denmark)

Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

2011-01-01

an assemblage, ecoregion or larger area always tends to be more unbalanced than expected from the phylogeny of species at the next more inclusive spatial scale. We conclude with a verbal model of mammalian macroevolution, which emphasizes the importance to diversification of accessing new regions...

Technology of mammalian cell encapsulation

NARCIS (Netherlands)

Uludag, H; De Vos, P; Tresco, PA

2000-01-01

Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

Functional Amyloid Formation within Mammalian Tissue.

Directory of Open Access Journals (Sweden)

2005-11-01

Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

Functional amyloid formation within mammalian tissue.

Directory of Open Access Journals (Sweden)

Douglas M Fowler

2006-01-01

Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

Mammalian RNA polymerase II core promoters: insights from genome-wide studies

DEFF Research Database (Denmark)

Sandelin, Albin; Carninci, Piero; Lenhard, Boris

2007-01-01

The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing...... in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing...

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

Science.gov (United States)

Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Possible involvement of SINEs in mammalian-specific brain formation.

Science.gov (United States)

Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

2008-03-18

Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

Bioenergetics of mammalian sperm capacitation.

Science.gov (United States)

Ferramosca, Alessandra; Zara, Vincenzo

2014-01-01

After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

Does autophagy have a license to kill mammalian cells?

Science.gov (United States)

Scarlatti, F; Granata, R; Meijer, A J; Codogno, P

2009-01-01

Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the loss of interaction with the extracellular matrix, and the toxicity of cancer therapies. During periods of nutrient starvation, stimulating macroautophagy provides the fuel required to maintain an active metabolism and the production of ATP. Macroautophagy can inhibit the induction of several forms of cell death, such as apoptosis and necrosis. However, it can also be part of the cascades of events that lead to cell death, either by collaborating with other cell death mechanisms or by causing cell death on its own. Loss of the regulation of bulk macroautophagy can prime self-destruction by cells, and some forms of selective autophagy and non-canonical forms of macroautophagy have been shown to be associated with cell demise. There is now mounting evidence that autophagy and apoptosis share several common regulatory elements that are crucial in any attempt to understand the dual role of autophagy in cell survival and cell death.

Atmospheric effects on laser eye safety and damage to instrumentation

Science.gov (United States)

Zilberman, Arkadi; Kopeika, Natan S.

2017-10-01

Electro-optical sensors as well as unprotected human eyes are extremely sensitive to laser radiation and can be permanently damaged from direct or reflected beams. Laser detector/eye hazard depends on the interaction between the laser beam and the media in which it traverses. The environmental conditions including terrain features, atmospheric particulate and water content, and turbulence, may alter the laser's effect on the detector/eye. It is possible to estimate the performance of an electro-optical system as long as the atmospheric propagation of the laser beam can be adequately modeled. More recent experiments and modeling of atmospheric optics phenomena such as inner scale effect, aperture averaging, atmospheric attenuation in NIR-SWIR, and Cn2 modeling justify an update of previous eye/detector safety modeling. In the present work, the influence of the atmospheric channel on laser safety for personnel and instrumentation is shown on the basis of theoretical and experimental data of laser irradiance statistics for different atmospheric conditions. A method for evaluating the probability of damage and hazard distances associated with the use of laser systems in a turbulent atmosphere operating in the visible and NIR-SWIR portions of the electromagnetic spectrum is presented. It can be used as a performance prediction model for directed energy engagement of ground-based or air-based systems.

Rim Structure, Stratigraphy, and Aqueous Alteration Exposures Along Opportunity Rover's Traverse of the Noachian Endeavour Crater

Science.gov (United States)

Crumpler, L.S.; Arvidson, R. E.; Golombek, M.; Grant, J. A.; Jolliff, B. L.; Mittlefehldt, D. W.

2017-01-01

The Mars Exploration Rover Opportunity has traversed 10.2 kilometers along segments of the west rim of the 22-kilometer-diameter Noachian Endeavour impact crater as of sol 4608 (01/09/17). The stratigraphy, attitude of units, lithology, and degradation state of bedrock outcrops exposed on the crater rim have been examined in situ and placed in geologic context. Structures within the rim and differences in physical properties of the identified lithologies have played important roles in localizing outcrops bearing evidence of aqueous alteration.

An FMM based on dual tree traversal for many-core architectures

KAUST Repository

Yokota, Rio

2013-09-01

The present work attempts to integrate the independent efforts in the fast N-body community to create the fastest N-body library for many-core and heterogenous architectures. Focus is placed on low accuracy optimizations, in response to the recent interest to use FMM as a preconditioner for sparse linear solvers. A direct comparison with other state-of-the-art fast N-body codes demonstrates that orders of magnitude increase in performance can be achieved by careful selection of the optimal algorithm and low-level optimization of the code. The current N-body solver uses a fast multipole method with an efficient strategy for finding the list of cell-cell interactions by a dual tree traversal. A task-based threading model is used to maximize thread-level parallelism and intra-node load-balancing. In order to extract the full potential of the SIMD units on the latest CPUs, the inner kernels are optimized using AVX instructions.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

Science.gov (United States)

Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

Directory of Open Access Journals (Sweden)

Giuseppe Scapigliati

2018-05-01

Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

Systematic measurements of transient fields for W, Os and Pt ions traversing Fe

International Nuclear Information System (INIS)

Stuchbery, A.E.; Heseltine, T.H.; Anderssen, S.S.; Bolotin, H.H.; Byrne, A.P.; Fabricius, B.; Kibedi, T.

1994-01-01

Transient magnetic fields were measured for W, Os and Pt ions traversing iron hosts with average velocities in the range from approximately 1.6 v 0 to 4.8 v 0 (v 0 = c/137, Bohr velocity). Transient fields for W and Os in Fe are consistent with behaviour found for lighter rare-earth ions and are about 20% stronger than those for Pt in Fe over the majority of the velocity range examined. A measurement was made to confirm that possible heavy-ion beam induced attenuations of the transient field are negligible for low-velocity Pt ions excited by Ni beams. Results are discussed in terms of both empirical and model-based parameterizations of the transient field strength. (orig.)

Proceedings 3rd Workshop on GRAPH Inspection and Traversal Engineering (GRAPHITE 2014)

DEFF Research Database (Denmark)

2014-01-01

is to foster the convergence on research interests from several communities dealing with graph analysis in all its forms in computer science, with a particular attention to software development and analysis. Graphs are used to represent data and processes in many application areas, and they are subjected......These are the proceedings of the Third Workshop on GRAPH Inspection and Traversal Engineering (GRAPHITE 2014), which took place on April 5, 2014 in Grenoble, France, as a satellite event of the 17th European Joint Conferences on Theory and Practice of Software (ETAPS 2014). The aim of GRAPHITE...... to various computational algorithms in order to analyze them. Just restricting the attention to the analysis of software, graph analysis algorithms are used, for instance, to verify properties using model checking techniques that explore the system's state space graph or static analysis techniques based...

Estimation of relative biological effectiveness for low energy protons using cytogenetic end points in mammalian cells

International Nuclear Information System (INIS)

Bhat, N.N.; Nairy, Rajesh; Chaurasia, Rajesh; Desai, Utkarsha; Shirsath, K.B.; Anjaria, K.B.; Sreedevi, B.

2013-01-01

A facility has been designed and developed to facilitate irradiation of biological samples to proton beam using folded tandem ion accelerator (FOTIA) at BARC. The primary proton beam from the accelerator was diffused using gold foil and channelled through a drift tube. Scattered beam was monitored and calibrated. Uniformity and dosimetry studies were conducted to calibrate the setup for precise irradiation of mammalian cells. Irradiation conditions and geometry were optimized for mammalian cells and other biological samples in thin layer. The irradiation facility is housed in a clean air laminar flow to help exposure of samples in aseptic conditions. The set up has been used for studying various radiobiological endpoints in many biological model systems. CHO, MCF-7, A-549 and INT-407 cell lines were studied in the present investigation using micronucleus (MN) induction as an indicator of radiation damage. The mammalian cells grown on petri plates to about 40 % confluence (log phase) were exposed to proton beam of known doses in the range of 0.1 to 2 Gy. The dose estimation was done based on specific ionization in cell medium. Studies were also conducted using 60 Co gamma radiation to compare the results. Linear quadratic response was observed for all the cell lines when exposed to 60 Co gamma radiation. In contrast, linear response was observed for proton beam. In addition, very significant increase in the MN yield was observed for proton beam compared to 60 Co gamma radiation. Estimated α and β values for CHO cells is found to be 0.02±0.003 Gy-1 and 0.042±0.006 Gy-2 respectively for 60 Co gamma radiation. For proton beam, estimated α for linear fit is found to be 0.37±0.011 Gy-1. Estimated RBE was found to be in the range of 4-8 for all the cell lines and dose ranges studied. In conclusion, the proton irradiation facility developed for mammalian cells has helped to study various radiobiological endpoints. In this presentation, facility description, MN as

Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation

Directory of Open Access Journals (Sweden)

Atilgan Yilmaz

2015-11-01

Full Text Available In contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e., reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, induced activation of dedifferentiation responses in mammalian tissues holds an immense promise for regenerative medicine. Here we demonstrate that ectopic expression of Msx2 in cultured mouse myotubes recapitulates several aspects of amphibian muscle dedifferentiation. We found that MSX2, but not MSX1, leads to cellularization of myotubes and downregulates the expression of myotube markers, such as MHC, MRF4 and myogenin. RNA sequencing of myotubes ectopically expressing Msx2 showed downregulation of over 500 myotube-enriched transcripts and upregulation of over 300 myoblast-enriched transcripts. MSX2 selectively downregulated expression of Ptgs2 and Ptger4, two members of the prostaglandin pathway with important roles in myoblast fusion during muscle differentiation. Ectopic expression of Msx2, as well as Msx1, induced partial cell cycle re-entry of myotubes by upregulating CyclinD1 expression but failed to initiate S-phase. Finally, MSX2-induced dedifferentiation in mouse myotubes could be recapitulated by a pharmacological treatment with trichostatin A (TSA, bone morphogenetic protein 4 (BMP4 and fibroblast growth factor 1 (FGF1. Together, these observations indicate that MSX2 is a major driver of dedifferentiation in mammalian muscle cells.

Ionizing radiation-induced DNA damage and its repair in human cells. Final performance report, July 1992 - June 1995

International Nuclear Information System (INIS)

Dizdaroglu, M.

1995-01-01

The studies of DNA damage in living cells in vitro and in vivo were continued. A variety of systems including cultured mammalian cells, animals, and human tissues were used to conduct these studies. In addition, enzymatic repair of DNA base damage was studied using several DNA glycosylases. To this end, substrate specificities of these enzymes were examined in terms of a large number of base lesions in DNA. In the first phase of the studies, the author sought to introduce improvements to his methodologies for measurement of DNA damage using the technique of gas chromatography/mass spectrometry (GC/MS). In particular, the quantitative measurement of DNA base damage and DNA-protein crosslinks was improved by incorporation of isotope-dilution mass spectrometry into the methodologies. This is one of the most accurate techniques for quantification of organic compounds. Having improved the measurement technique, studies of DNA damage in living cells and DNA repair by repair enzymes were pursued. This report provides a summary of these studies with references to the original work

Titanium dioxide induced cell damage: A proposed role of the carboxyl radical

Energy Technology Data Exchange (ETDEWEB)

Dodd, Nicholas J.F. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom); Jha, Awadhesh N. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom)], E-mail: a.jha@plymouth.ac.uk

2009-01-15

Titanium dioxide (TiO{sub 2}) nanoparticles have been shown to be genotoxic to cells exposed to ultraviolet A (UVA) radiation. Using the technique of electron spin resonance (ESR) spin trapping, we have confirmed that the primary damaging species produced on irradiation of TiO{sub 2} nanoparticles is the hydroxyl (OH) radical. We have applied this technique to TiO{sub 2}-treated fish and mammalian cells under in vitro conditions and observed the additional formation of carboxyl radical anions (CO{sub 2}{sup -}) and superoxide radical anions (O{sub 2}{sup -}). This novel finding suggests a hitherto unreported pathway for damage, involving primary generation of OH radicals in the cytoplasm, which react to give CO{sub 2}{sup -} radicals. The latter may then react with cellular oxygen to form O{sub 2}{sup -} and genotoxic hydrogen peroxide (H{sub 2}O{sub 2})

Traversing field of view and AR-PIV for mid-field wake vortex investigation in a towing tank

Science.gov (United States)

Scarano, F.; van Wijk, C.; Veldhuis, L. L. M.

2002-08-01

Wake vortex flow experiments are performed in a water tank where a 1:48 scaled model of a large transport aircraft A340-300 is towed at the speed of 3 and 5 ms-1 with values of the angle of attack α={2°, 4°, 8°}. Particle image velocimetry (PIV) measurements are performed in a plane perpendicular to the towing direction describing the streamwise component of the wake vorticity. The instantaneous field of view (I-FOV) is traversed vertically with an underwater moving-camera device tracking the vortex core during the downward motion. An adaptive resolution (AR) image-processing technique is introduced that enhances the PIV interrogation in terms of spatial resolution and accuracy. The main objectives of the investigation are to demonstrate the applicability of PIV diagnostics in wake vortex research with towing-tank facilities. The specific implementation of the traversing field-of-view (T-FOV) technique and the AR image processing are driven by the need to characterize the vortex wake global properties as well as the vortex decay phenomenon in the mid- and far-field. Relevant aerodynamic information is obtained in the mid-field where the time evolution of the vortex structure (core radius and tangential velocity) and of the overall vortex wake (vortex trajectory, descent velocity, circulation) are discussed.

[Investigation of new classification and repair methods for fingertip traverse amputation].

Science.gov (United States)

Zhou, Xiao; Xu, Yajun; Rui, Yongjun; Yao, Qun

2008-09-01

To investigate new classification and repair methods for the traverse amputated fingertip. From March 2000 to October 2006, 20 cases of 20 fingers with traverse amputated fingertip, including 13 males and 7 females aged 17-47 years, were treated. Twenty patients (9 crush injuries, 5 cutting injuries and 6 sawing injuries) were classified into 4 types, namely type I (the distal one third of nail bed), type II (the middle of nail bed), type III (the proximal one third of nail bed), and type IV (the root of nail bed). There were 3 patients (2 index fingers and 1 little finger) of type I, 8 patients (2 thumbs, 3 index fingers and 3 middle fingers) of type II, 5 patients (3 index fingers, 1 ring finger and 1 little finger) of type III, and 4 patients (2 thumbs, 1 middle finger and 1 little finger) of type IV. The soft tissue defect ranged from 1.2 cm x 1.2 cm to 1.5 cm x 1.2 cm. The time from injury to surgery was 3-10 hours. Fingers of type I and type II were treated with forward flow axial flap and modified nail bed lengthening. Fingers of type III and type IV were treated with forward flow axial flap and partial nail bed replantation as well as modified nail bed lengthening. The flaps ranged in size from 1.5 cm x 1.2 cm to 2.0 cm x 1.4 cm. Twenty patients incisions healed by first intention and the flaps, nails and skin grafting survived. All donor sites healed by first intention. All patients were followed up for 2-6 months (4 months on average). The appearances of fingertips were good. The texture of the flap was soft, and the fingers had no tenderness and motor disturbance. The two-point discrimination was 4.5-6.5 mm. The finger nails of type I and type II extended 3-4 mm after operation, while the finger nails of type III and type IV extended 8-10 mm after operation. All finger nails were smooth and flat without pain. Hook nail happened in 1 case 6 months after operation. Classification of the injured fingers according to the condition of the amputation base is

Role of cyclins in controlling progression of mammalian spermatogenesis

OpenAIRE

WOLGEMUTH, DEBRA J.; MANTEROLA, MARCIA; VASILEVA, ANA

2013-01-01

Cyclins are key regulators of the mammalian cell cycle, functioning primarily in concert with their catalytic partners, the cyclin-dependent kinases (Cdks). While their function during mitosis in somatic cells has been extensively documented, their function during both mitosis and meiosis in the germ line is poorly understood. From the perspective of cell cycle regulation there are several aspects of mammalian spermatogenesis that suggest unique modes of regulation and hence, possible unique ...

Comparison of amphibian and mammalian thyroperoxidase ...

Science.gov (United States)

Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success.

Science.gov (United States)

Pérez-Cerezales, S; Martínez-Páramo, S; Beirão, J; Herráez, M P

2010-06-01

Mammalian spermatozoa undergo a strong selection process along the female tract to guarantee fertilization by good quality cells, but risks of fertilization with DNA-damaged spermatozoa have been reported. In contrast, most external fertilizers such as fish seem to have weaker selection procedures. This fact, together with their high prolificacy and external embryo development, indicates that fish could be useful for the study of the effects of sperm DNA damage on embryo development. We cryopreserved sperm from rainbow trout using egg yolk and low-density lipoprotein as additives to promote different rates of DNA damage. DNA fragmentation and oxidization were analyzed using comet assay with and without digestion with restriction enzymes, and fertilization trials were performed. Some embryo batches were treated with 3-aminobenzamide (3AB) to inhibit DNA repair by the poly (ADP-ribose) polymerase, which is an enzyme of the base excision repair pathway. Results showed that all the spermatozoa cryopreserved with egg yolk carried more than 10% fragmented DNA, maintaining fertilization rates of 61.1+/-2.3 but a high rate of abortions, especially during gastrulation, and only 14.5+/-4.4 hatching success. Furthermore, after 3AB treatment, hatching dropped to 3.2+/-2.2, showing that at least 10% DNA fragmentation was repaired. We conclude that trout sperm maintains its ability to fertilize in spite of having DNA damage, but that embryo survival is affected. Damage is partially repaired by the oocyte during the first cleavage. Important advantages of using rainbow trout for the study of processes related to DNA damage and repair during development have been reported.

Mammalian Sperm Motility: Observation and Theory

KAUST Repository

Gaffney, E.A.; Gadê lha, H.; Smith, D.J.; Blake, J.R.; Kirkman-Brown, J.C.

2011-01-01

the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian

1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

International Nuclear Information System (INIS)

NONE

1999-01-01

This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair

1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-02-12

This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

Stalled repair of lesions when present within a clustered DNA damage site

International Nuclear Information System (INIS)

Lomax, M.E.; Cunniffe, S.; O'Neill, P.

2003-01-01

Ionising radiation produces clustered DNA damages (two or more lesions within one or two helical turns of the DNA) which could challenge the repair mechanism(s) of the cell. Using purified base excision repair (BER) enzymes and synthetic oligonucleotides a number of recent studies have established the excision of a lesion within clustered damage sites is compromised. Evidence will be presented that the efficiency of repair of lesions within a clustered DNA damage site is reduced, relative to that of the isolated lesions, since the lifetime of both lesions is extended by up to four fold. Simple clustered damage sites, comprised of single-strand breaks, abasic sites and base damages, one or five bases 3' or 5' to each other, were synthesised in oligonucleotides and repair carried out in mammalian cell nuclear extracts. The rate of repair of the single-strand break/abasic site within these clustered damage sites is reduced, mainly due to inhibition of the DNA ligase. The mechanism of repair of the single-strand break/abasic site shows some asymmetry. Repair appears to be by the short-patch BER pathway when the lesions are 5' to each other. In contrast, when the lesions are 3' to each other repair appears to proceed along the long-patch BER pathway. The lesions within the cluster are processed sequentially, the single-strand break/abasic site being repaired before excision of 8-oxoG, limiting the formation of double-strand breaks to <2%. Stalled processing of clustered DNA damage extends the lifetime of the lesions to an extent that could have biological consequences, e.g. if the lesions are still present during transcription and/or at replication mutations could arise

Evolutionary dynamics of mammalian karyotypes

Directory of Open Access Journals (Sweden)

Carlo Alberto Redi

2012-12-01

Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

Experimental studies of the acoustic signature of proton beams traversing fluid media

International Nuclear Information System (INIS)

Levi, M.; Armstrong, T.; Baranger, H.; Bregman, M.; Mael, D.; Strait, J.; Sulak, L.; Bowen, T.; Pifer, B.; Polakos, P.; Bradner, H.; Parvulescu, A.; Jones, H.; Learned, J.

1978-01-01

This work establishes that a detectable sonic signal is produced by protons while traversing through or stopping in a fluid medium. Experiments exploring the global characteristics of both the acoustic generation mechanism and the radiation pattern were performed at three different accelerators. The results are consistent with a simple thermal model for the transformation of the energy of moving charged-particles into acoustic energy. This phenomenon could be exploited in several applications: (1) as a charged particle monitor in accelerator beams, (2) as a heavy-ion detector sensitive to nuclear charge, e.g., in measuring cosmic ray isotopes (3) as an inexpensive shower detector in massive neutrino detectors at the next generation of high-energy accelerators, e.g, the Fermilab energy doubler and (4) as the shower calorimeter (and perhaps the muon detector) in massive deep underwater detectors of cosmic neutrino and muon interactions

Structural differences between yeast and mammalian microtubules revealed by cryo-EM

Energy Technology Data Exchange (ETDEWEB)

Howes, Stuart C. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group; Geyer, Elisabeth A. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; LaFrance, Benjamin [Univ. of California, Berkeley, CA (United States). Molecular and Cell Biology Graduate Program; Zhang, Rui [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Kellogg, Elizabeth H. [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Westermann, Stefan [Univ. of Duisburg-Essen, Essen (Germany). Dept. of Molecular Genetics, Center for Medical Biotechnology; Rice, Luke M. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; Nogales, Eva [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular Biology and California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

2017-06-26

Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrations used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.

Spontaneous development of bilateral subdural hematomas in an infant with benign infantile hydrocephalus: color Doppler assessment of vessels traversing extra-axial spaces

Energy Technology Data Exchange (ETDEWEB)

Amodio, John; Spektor, Vadim; Pramanik, Bidyut; Rivera, Rafael; Pinkney, Lynne; Fefferman, Nancy [New York University Medical Center, Department of Radiology, New York, NY (United States)

2005-11-01

We present an infant with macrocrania, who initially demonstrated prominent extra-axial fluid collections on sonography of the brain, compatible with benign infantile hydrocephalus (BIH). Because of increasing macrocrania, a follow-up sonogram of the brain was performed; it revealed progressive enlargement of the extra-axial spaces, which now had echogenic debris. Color Doppler US showed bridging veins traversing these extra-axial spaces, so it was initially thought that these spaces were subarachnoid in nature (positive cortical vein sign). However, an arachnoid membrane was identified superior to the cortex, and there was compression of true cortical vessels beneath this dural membrane. An MRI of the brain showed the extra-axial spaces to represent bilateral subdural hematomas. The pathogenesis of spontaneous development of the subdural hematomas, in the setting of BIH, is discussed. We also emphasize that visualizing traversing bridging veins through extra-axial spaces does not necessarily imply that these spaces are subarachnoid in origin. (orig.)

Role of Notch signaling in the mammalian heart

Energy Technology Data Exchange (ETDEWEB)

Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

2013-12-12

Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage

International Nuclear Information System (INIS)

Warters, R.L.; Hofer, K.G.; Harris, C.R.; Smith, J.M.

1978-01-01

Synchronized suspension cultures of Chinese hamster ovary cells (CHO) were labeled with various doses of 3 H-thymidine or 125 I-iododeoxyuridine to evaluate the cytocidal effects of intranuclear radionuclide decay. Damage produced by radionuclide decay outside the cell nucleus was studied on cells exposed to 125 I labeled, monovalent concanavalin A. After labeling, the cells were resynchronized in G 1 -phase and incubated for 36 h at 4 0 C to permit dose accumulation. Cell lethality was evaluated by the standard colony assay. Based on radionuclide incorporation data, cellular dimensions, and subcellular radionuclide distributions, the cumulative dose to whole cells, cell nuclei, and cellular cytoplasm was calculated from the known decay properties of 3 H and 125 I. (Auth.)

Coordinate to Guard: Crosstalk of Phosphorylation, Sumoylation, and Ubiquitylation in DNA Damage Response

International Nuclear Information System (INIS)

Kuo, Ching-Ying; Shieh, Christine; Cai, Fei; Ann, David Kong

2012-01-01

Small ubiquitin-like modifier-1/2/3 (SUMO-1/2/3) and ubiquitin share similar structure and utilize analogous machinery for protein lysine conjugation. Although sumoylation and ubiquitylation have distinct functions, they are often tightly associated with each other to fine-tune protein fate in transducing signals to regulate a wide variety of cellular functions, including DNA damage response, cell proliferation, DNA replication, embryonic development, and cell differentiation. In this Perspective, we specifically highlight the role of sumoylation and ubiquitylation in ataxia-telangiectasia mutated (ATM) signaling in response to DNA double-strand breaks and hypothesize that ATM-induced phosphorylation is a unique node in regulating SUMO-targeted ubiquitylation in mammalian cells to combat DNA damage and to maintain genome integrity. A potential role for the coordination of three types of post-translational modification in dictating the tempo and extent of cellular response to genotoxic stress is speculated.

Coordinate to Guard: Crosstalk of Phosphorylation, Sumoylation, and Ubiquitylation in DNA Damage Response

Energy Technology Data Exchange (ETDEWEB)

Kuo, Ching-Ying [Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA (United States); Department of Molecular Pharmacology, Beckman Research Institute of City of Hope, Duarte, CA (United States); Shieh, Christine; Cai, Fei [Eugene and Ruth Roberts Summer Student Academy, Beckman Research Institute of City of Hope, Duarte, CA (United States); Ann, David Kong, E-mail: dann@coh.org [Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA (United States); Department of Molecular Pharmacology, Beckman Research Institute of City of Hope, Duarte, CA (United States); Eugene and Ruth Roberts Summer Student Academy, Beckman Research Institute of City of Hope, Duarte, CA (United States)

2012-01-19

Small ubiquitin-like modifier-1/2/3 (SUMO-1/2/3) and ubiquitin share similar structure and utilize analogous machinery for protein lysine conjugation. Although sumoylation and ubiquitylation have distinct functions, they are often tightly associated with each other to fine-tune protein fate in transducing signals to regulate a wide variety of cellular functions, including DNA damage response, cell proliferation, DNA replication, embryonic development, and cell differentiation. In this Perspective, we specifically highlight the role of sumoylation and ubiquitylation in ataxia-telangiectasia mutated (ATM) signaling in response to DNA double-strand breaks and hypothesize that ATM-induced phosphorylation is a unique node in regulating SUMO-targeted ubiquitylation in mammalian cells to combat DNA damage and to maintain genome integrity. A potential role for the coordination of three types of post-translational modification in dictating the tempo and extent of cellular response to genotoxic stress is speculated.

Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

Science.gov (United States)

Karten, Harvey J.

2015-01-01

The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

Opportunity Mars Rover mission: Overview and selected results from Purgatory ripple to traverses to Endeavour crater

Science.gov (United States)

Arvidson, R. E.; Ashley, James W.; Bell, J.F.; Chojnacki, M.; Cohen, J.; Economou, T.E.; Farrand, W. H.; Fergason, R.; Fleischer, I.; Geissler, P.; Gellert, Ralf; Golombek, M.P.; Grotzinger, J.P.; Guinness, E.A.; Haberle, R.M.; Herkenhoff, K. E.; Herman, J.A.; Iagnemma, K.D.; Jolliff, B.L.; Johnson, J. R.; Klingelhofer, G.; Knoll, A.H.; Knudson, A.T.; Li, R.; McLennan, S.M.; Mittlefehldt, D. W.; Morris, R.V.; Parker, T.J.; Rice, M.S.; Schroder, C.; Soderblom, L.A.; Squyres, S. W.; Sullivan, R.J.; Wolff, M.J.

2011-01-01

Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.

Foliar Nutritional Quality Explains Patchy Browsing Damage Caused by an Invasive Mammal.

Directory of Open Access Journals (Sweden)

Hannah R Windley

Full Text Available Introduced herbivores frequently inflict significant, yet patchy damage on native ecosystems through selective browsing. However, there are few instances where the underlying cause of this patchy damage has been revealed. We aimed to determine if the nutritional quality of foliage could predict the browsing preferences of an invasive mammalian herbivore, the common brushtail possum (Trichosurus vulpecula, in a temperate forest in New Zealand. We quantified the spatial and temporal variation in four key aspects of the foliar chemistry (total nitrogen, available nitrogen, in vitro dry matter digestibility and tannin effect of 275 trees representing five native tree species. Simultaneously, we assessed the severity of browsing damage caused by possums on those trees in order to relate selective browsing to foliar nutritional quality. We found significant spatial and temporal variation in nutritional quality among individuals of each tree species examined, as well as among tree species. There was a positive relationship between the available nitrogen concentration of foliage (a measure of in vitro digestible protein and the severity of damage caused by browsing by possums. This study highlights the importance of nutritional quality, specifically, the foliar available nitrogen concentration of individual trees, in predicting the impact of an invasive mammal. Revealing the underlying cause of patchy browsing by an invasive mammal provides new insights for conservation of native forests and targeted control of invasive herbivores in forest ecosystems.

Benthic dinitrogen fixation traversing the oxygen minimum zone off Mauritania (NW Africa)

DEFF Research Database (Denmark)

Gier, Jessica; Löscher, Carolin R.; Dale, Andrew W.

2017-01-01

metabolisms, such as sulfate reduction. In the present study, benthic N2 fixation together with sulfate reduction and other heterotrophic metabolisms were investigated at six station between 47 and 1,108 m water depth along the 18°N transect traversing the highly productive upwelling region known...... as Mauritanian oxygen minimum zone (OMZ). Bottom water oxygen concentrations ranged between 30 and 138 μM. Benthic N2 fixation determined by the acetylene reduction assay was detected at all stations with highest rates (0.15 mmol m-2 d-1) on the shelf (47 and 90 m water depth) and lowest rates (0.08 mmol m-2 d-1......) below 412 m water depth. The biogeochemical data suggest that part of the N2 fixation could be linked to sulfate- and iron-reducing bacteria. Molecular analysis of the key functional marker gene for N2 fixation, nifH, confirmed the presence of sulfate- and iron-reducing diazotrophs. High N2 fixation...

Evaluation of Mammalian Interspersed Repeats to investigate the goat genome

Directory of Open Access Journals (Sweden)

P. Mariani

2010-01-01

Full Text Available Among the repeated sequences present in most eukaryotic genomes, SINEs (Short Interspersed Nuclear Elements are widely used to investigate evolution in the mammalian order (Buchanan et al., 1999. One family of these repetitive sequences, the MIR (Mammalian Interspersed Repeats; Jurka et al., 1995, is ubiquitous in all mammals.MIR elements are tRNA-derived SINEs and are identifiable by a conserved core region of about 70 nucleotides.

Chronic Alcohol Consumption Alters Mammalian Target of Rapamycin (mTOR), Reduces Ribosomal p70S6 Kinase and p4E-BP1 Levels in Mouse Cerebral Cortex

OpenAIRE

Li, Qun; Ren, Jun

2007-01-01

Reduced insulin sensitivity following chronic alcohol consumption may contribute to alcohol-induced brain damage although the underlying mechanism(s) has not been elucidated. This study was designed to examine the effect of chronic alcohol intake on insulin signaling in mouse cerebral cortex. FVB mice were fed with a 4% alcohol diet for 16 weeks. Insulin receptor substrates (IRS-1, IRS-2) and post-receptor signaling molecules Akt, mammalian target of rapamycin (mTOR), ribosomal p70s6 kinase (...

Adaptation of Escherichia coli traversing from the faecal environment to the urinary tract

DEFF Research Database (Denmark)

Nielsen, Karen L.; Stegger, Marc; Godfrey, Paul A.

2016-01-01

The majority of extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTI) are found in the patient’s own gut flora, but only limited knowledge is available on the potential adaptation that may occur in the bacteria in order to traverse the perineum and successfully...... infect the urinary tract. Here, matching pairs of faecal and UTI isolates from 42 patients were compared pairwise using in-depth whole-genome sequencing to investigate whether genetic changes were evident for successful colonization in these two different environments. The identified non...... in virulence potential were observed in a mouse UTI model for five matching faecal and UTI isolates with or without mutations in antigen 43 and haemolysin B. Variations in plasmid content were observed in only four of the 42 pairs. Although, we observed mutations in known UTI virulence genes for a few pairs...

A multistep damage recognition mechanism for global genomic nucleotide excision repair.

Science.gov (United States)

Sugasawa, K; Okamoto, T; Shimizu, Y; Masutani, C; Iwai, S; Hanaoka, F

2001-03-01

A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.

Structure and function of mammalian cilia

DEFF Research Database (Denmark)

Satir, Peter; Christensen, Søren T

2008-01-01

In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...

Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol

International Nuclear Information System (INIS)

Mitchell, J.B.; DeGraff, W.; Kaufman, D.; Krishna, M.C.; Samuni, A.; Finkelstein, E.; Ahn, M.S.; Hahn, S.M.; Gamson, J.; Russo, A.

1991-01-01

Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress

Transient-field strength measurements for 52Cr traversing Fe hosts at high velocity and polarization transfer mechanisms

International Nuclear Information System (INIS)

Stuchbery, A.E.; Doran, C.E.; Byrne, A.P.; Bolotin, H.H.; Dracoulis, G.D.

1986-12-01

Transient-field strengths were measured for 52 Cr ions traversing polarized Fe hosts at velocities up to 12v>=o (v>=o = c/137 = Bohr velocity). The results are compared with predictions of various transient field parametrizations and discussed in terms of possible mechanisms by which polarization might be transferred from the Fe host to inner vacancies of the moving Cr ions. The g-factor of the first 2 + state of 52 Cr was also measured by the transient field technique and found to be in accord with shell-model calculations

Mammalian Sperm Motility: Observation and Theory

KAUST Repository

Gaffney, E.A.

2011-01-21

Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.

Damage pattern as a function of radiation quality and other factors.

Science.gov (United States)

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex

Archetype, adaptation and the mammalian heart

NARCIS (Netherlands)

Meijler, F.L.; Meijler, T.D.

2011-01-01

Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural

Identification of the Elusive Mammalian Enzyme Phosphatidylcholine-Specific Phospholipase C

Science.gov (United States)

2015-09-01

Summary of Results. Task 1. To identify mammalian PC- PLC . Based on results published by other groups, we proposed to identify candidate PC- PLC mRNAs by...establishing the role of the elusive mammalian protein, phosphatidycholine- specific phospholipase C (PC- PLC ) in the inflammatory processes involved in...progression of rheumatoid arthritis (RA). Thus, the main scopes of this proposal are: 1. to identify the PC- PLC gene and protein; and 2. to test PC- PLC

Duplex Interrogation by a Direct DNA Repair Protein in Search of Base Damage

Science.gov (United States)

Yi, Chengqi; Chen, Baoen; Qi, Bo; Zhang, Wen; Jia, Guifang; Zhang, Liang; Li, Charles J.; Dinner, Aaron R.; Yang, Cai-Guang; He, Chuan

2012-01-01

ALKBH2 is a direct DNA repair dioxygenase guarding mammalian genome against N1-methyladenine, N3-methylcytosine, and 1,N6-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 displays two novel features: i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability; ii) ALKBH2 does not have nor need a “damage-checking site”, which is critical for preventing spurious base-cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly. PMID:22659876

γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

DEFF Research Database (Denmark)

Daneshvar, B.; Frandsen, H.; Autrup, Herman

1997-01-01

proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found......Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...

InXy and SeXy, compact heterologous reporter proteins for mammalian cells.

Science.gov (United States)

Fluri, David A; Kelm, Jens M; Lesage, Guillaume; Baba, Marie Daoud-El; Fussenegger, Martin

2007-10-15

Mammalian reporter proteins are essential for gene-function analysis, drugscreening initiatives and as model product proteins for biopharmaceutical manufacturing. Bacillus subtilis can maintain its metabolism by secreting Xylanase A (XynA), which converts xylan into shorter xylose oligosaccharides. XynA is a family 11 xylanase monospecific for D-xylose containing substrates. Mammalian cells transgenic for constitutive expression of wild-type xynA showed substantial secretion of this prokaryotic enzyme. Deletion analysis confirmed that a prokaryotic signal sequence encoded within the first 81 nucleotides was compatible with the secretory pathway of mammalian cells. Codon optimization combined with elimination of the prokaryotic signal sequence resulted in an exclusively intracellular mammalian Xylanase A variant (InXy) while replacement by an immunoglobulin-derived secretion signal created an optimal secreted Xylanase A derivative (SeXy). A variety of chromogenic and fluorescence-based assays adapted for use with mammalian cells detected InXy and SeXy with high sensitivity and showed that both reporter proteins resisted repeated freeze/thaw cycles, remained active over wide temperature and pH ranges, were extremely stable in human serum stored at room temperature and could independently be quantified in samples also containing other prominent reporter proteins such as the human placental alkaline phosphatase (SEAP) and the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY). Glycoprofiling revealed that SeXy produced in mammalian cells was N- glycosylated at four different sites, mutation of which resulted in impaired secretion. SeXy was successfully expressed in a variety of mammalian cell lines and primary cells following transient transfection and transduction with adeno-associated virus particles (AAV) engineered for constitutive SeXy expression. Intramuscular injection of transgenic AAVs into mice showed significant SeXy levels in the bloodstream

Direct Capture of Functional Proteins from Mammalian Plasma Membranes into Nanodiscs.

Science.gov (United States)

Roy, Jahnabi; Pondenis, Holly; Fan, Timothy M; Das, Aditi

2015-10-20

Mammalian plasma membrane proteins make up the largest class of drug targets yet are difficult to study in a cell free system because of their intransigent nature. Herein, we perform direct encapsulation of plasma membrane proteins derived from mammalian cells into a functional nanodisc library. Peptide fingerprinting was used to analyze the proteome of the incorporated proteins in nanodiscs and to further demonstrate that the lipid composition of the nanodiscs directly affects the class of protein that is incorporated. Furthermore, the functionality of the incorporated membrane proteome was evaluated by measuring the activity of membrane proteins: Na(+)/K(+)-ATPase and receptor tyrosine kinases. This work is the first report of the successful establishment and characterization of a cell free functional library of mammalian membrane proteins into nanodiscs.

Current perspectives of CASA applications in diverse mammalian spermatozoa.

Science.gov (United States)

van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

2018-03-26

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

The effect of laser power, traverse velocity and spot size on the peel resistance of a polypropylene/adhesive bond

OpenAIRE

Dowding, Colin; Dowding, Robert; Franceschini, Federica; Griffiths, Jonathan David

2015-01-01

Abstract The mean peel resistance force achieved with respect to variation in the laser power, incident spot traverse velocity and incident spot diameter between linear low density polyethylene film backed by a thin commercial adhesive coating that were bonded to a polypropylene substrate via thermal activation provided by a 27W CO 2 laser is discussed in this work. The results gathered for this work have been used to generate a novel empirical tool that predicts the CO...

Non-linear leak currents affect mammalian neuron physiology

Directory of Open Access Journals (Sweden)

Shiwei eHuang

2015-11-01

Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

Science.gov (United States)

Cassone, V M; Speh, J C; Card, J P; Moore, R Y

1988-01-01

A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

Musculoskeletal networks reveal topological disparity in mammalian neck evolution.

Science.gov (United States)

Arnold, Patrick; Esteve-Altava, Borja; Fischer, Martin S

2017-12-13

The increase in locomotor and metabolic performance during mammalian evolution was accompanied by the limitation of the number of cervical vertebrae to only seven. In turn, nuchal muscles underwent a reorganization while forelimb muscles expanded into the neck region. As variation in the cervical spine is low, the variation in the arrangement of the neck muscles and their attachment sites (i.e., the variability of the neck's musculoskeletal organization) is thus proposed to be an important source of neck disparity across mammals. Anatomical network analysis provides a novel framework to study the organization of the anatomical arrangement, or connectivity pattern, of the bones and muscles that constitute the mammalian neck in an evolutionary context. Neck organization in mammals is characterized by a combination of conserved and highly variable network properties. We uncovered a conserved regionalization of the musculoskeletal organization of the neck into upper, mid and lower cervical modules. In contrast, there is a varying degree of complexity or specialization and of the integration of the pectoral elements. The musculoskeletal organization of the monotreme neck is distinctively different from that of therian mammals. Our findings reveal that the limited number of vertebrae in the mammalian neck does not result in a low musculoskeletal disparity when examined in an evolutionary context. However, this disparity evolved late in mammalian history in parallel with the radiation of certain lineages (e.g., cetartiodactyls, xenarthrans). Disparity is further facilitated by the enhanced incorporation of forelimb muscles into the neck and their variability in attachment sites.

Identification of mammalian proteins cross-linked to DNA by ionizing radiation.

Science.gov (United States)

Barker, Sharon; Weinfeld, Michael; Zheng, Jing; Li, Liang; Murray, David

2005-10-07

Ionizing radiation (IR) is an important environmental risk factor for various cancers and also a major therapeutic agent for cancer treatment. Exposure of mammalian cells to IR induces several types of damage to DNA, including double- and single-strand breaks, base and sugar damage, as well as DNA-DNA and DNA-protein cross-links (DPCs). Little is known regarding the biological consequences of DPCs. Identifying the proteins that become cross-linked to DNA by IR would be an important first step in this regard. We have therefore undertaken a proteomics study to isolate and identify proteins involved in IR-induced DPCs. DPCs were induced in AA8 Chinese hamster ovary or GM00637 human fibroblast cells using 0-4 gray of gamma-rays under either aerated or hypoxic conditions. DPCs were isolated using a recently developed method, and proteins were identified by mass spectrometry. We identified 29 proteins as being cross-linked to DNA by IR under aerated and/or hypoxic conditions. The identified proteins include structural proteins, actin-associated proteins, transcription regulators, RNA-splicing components, stress-response proteins, cell cycle regulatory proteins, and GDP/GTP-binding proteins. The involvement of several proteins (actin, histone H2B, and others) in DPCs was confirmed by using Western blot analysis. The dose responsiveness of DPC induction was examined by staining one-dimensional SDS-polyacrylamide gels with SYPRO Tangerine followed by analysis using fluorescence imaging. Quantitation of the fluorescence signal indicated no significant difference in total yields of IR-induced DPCs generated under aerated or hypoxic conditions, although differences were observed for several individual protein bands.

Detection of tundra trail damage near Barrow, Alaska using remote imagery

Science.gov (United States)

Hinkel, K. M.; Eisner, W. R.; Kim, C. J.

2017-09-01

In the past several decades, the use of all-terrain vehicles (ATVs) has proliferated in many Arctic communities in North America. One example is the village of Barrow, Alaska. This coastal community has only local roads, so all access to the interior utilizes off-road machines. These 4-wheel vehicles are the primary means of tundra traverse and transport in summer by hunters and berry-pickers, and by village residents accessing summer camps. Traveling cross-country is difficult due to the large number of thermokarst lakes, wetlands, and streams, and tundra trails tend to follow dryer higher ground while avoiding areas of high microrelief such as high-centered ice-wedge polygons. Thus, modern ATV trails tend to follow the margins of drained or partially drained thermokarst lake basins where it is flat and relatively dry, and these trails are heavily used. The deeply-ribbed tires of the heavy and powerful ATVs cause damage by destroying the vegetation and disturbing the underlying organic soil. Exposure of the dark soil enhances summer thaw and leads to local thermokarst of the ice-rich upper permafrost. The damage increases over time as vehicles continue to follow the same track, and sections eventually become unusable; this is especially true where the trail crosses ice-wedge troughs. Deep subsidence in the ponded troughs results in ATV users veering to avoid the wettest area, which leads to a widening of the damaged area. Helicopter surveys, site visits, and collection of ground penetrating radar data were combined with time series analysis of high-resolution aerial and satellite imagery for the period 1955-2014. The analysis reveals that there are 507 km of off-road trails on the Barrow Peninsula. About 50% of the total trail length was developed before 1955 in association with resource extraction, and an additional 40% were formed between 1979 and 2005 by ATVs. Segments of the more modern trail are up to 100 m wide. Damage to the tundra is especially pronounced

Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

International Nuclear Information System (INIS)

Vázquez-Iglesias, Lorena; Lostalé-Seijo, Irene; Martínez-Costas, José; Benavente, Javier

2012-01-01

A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells.

Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

Energy Technology Data Exchange (ETDEWEB)

Vazquez-Iglesias, Lorena; Lostale-Seijo, Irene; Martinez-Costas, Jose [Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, y Centro Singular de Investigacion en Quimica Biologica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Benavente, Javier, E-mail: franciscojavier.benavente@usc.es [Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, y Centro Singular de Investigacion en Quimica Biologica y Materiales Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782-Santiago de Compostela (Spain)

2012-10-25

A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells.

The different roles of selective autophagic protein degradation in mammalian cells.

Science.gov (United States)

Wang, Da-wei; Peng, Zhen-ju; Ren, Guang-fang; Wang, Guang-xin

2015-11-10

Autophagy is an intracellular pathway for bulk protein degradation and the removal of damaged organelles by lysosomes. Autophagy was previously thought to be unselective; however, studies have increasingly confirmed that autophagy-mediated protein degradation is highly regulated. Abnormal autophagic protein degradation has been associated with multiple human diseases such as cancer, neurological disability and cardiovascular disease; therefore, further elucidation of protein degradation by autophagy may be beneficial for protein-based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA) can both participate in selective protein degradation in mammalian cells, but the process is quite different in each case. Here, we summarize the various types of macroautophagy and CMA involved in determining protein degradation. For this summary, we divide the autophagic protein degradation pathways into four categories: the post-translational modification dependent and independent CMA pathways and the ubiquitin dependent and independent macroautophagy pathways, and describe how some non-canonical pathways and modifications such as phosphorylation, acetylation and arginylation can influence protein degradation by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can serve as either diagnostics or therapeutic targets in different human diseases.

UVC-induced stress granules in mammalian cells.

Directory of Open Access Journals (Sweden)

Mohamed Taha Moutaoufik

Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

Dedifferentiation and proliferation of mammalian cardiomyocytes.

Directory of Open Access Journals (Sweden)

Yiqiang Zhang

2010-09-01

Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

Mammalian niche conservation through deep time.

Directory of Open Access Journals (Sweden)

Larisa R G DeSantis

Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

Ecology and evolution of mammalian biodiversity.

Science.gov (United States)

Jones, Kate E; Safi, Kamran

2011-09-12

Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future.

Ecology and evolution of mammalian biodiversity

Science.gov (United States)

Jones, Kate E.; Safi, Kamran

2011-01-01

Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

Application of the CometChip platform to assess DNA damage in field-collected blood samples from turtles.

Science.gov (United States)

Sykora, Peter; Chiari, Ylenia; Heaton, Andrew; Moreno, Nickolas; Glaberman, Scott; Sobol, Robert W

2018-05-01

DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism-induced oxidative damage that can lead to single-strand and double-strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra-violet light, can also contribute to exogenously derived DNA damage. We previously validated a novel, high through-put approach to measure levels of DNA damage in cultured mammalian cells. This new CometChip Platform builds on the classical single cell gel electrophoresis or comet methodology used extensively in environmental toxicology and molecular biology. We asked whether the CometChip Platform could be used to measure DNA damage in samples derived from environmental field studies. To this end, we determined that nucleated erythrocytes from multiple species of turtle could be successfully evaluated in the CometChip Platform to quantify levels of DNA damage. In total, we compared levels of DNA damage in 40 animals from two species: the box turtle (Terrapene carolina) and the red-eared slider (Trachemys scripta elegans). Endogenous levels of DNA damage were identical between the two species, yet we did discover some sex-linked differences and changes in DNA damage accumulation. Based on these results, we confirm that the CometChip Platform allows for the measurement of DNA damage in a large number of samples quickly and accurately, and is particularly adaptable to environmental studies using field-collected samples. Environ. Mol. Mutagen. 59:322-333, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Prdm9 controls activation of mammalian recombination hotspots.

Science.gov (United States)

Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

2010-02-12

Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

Locomotor circuits in the mammalian spinal cord

DEFF Research Database (Denmark)

Kiehn, Ole

2006-01-01

Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network struct...

Towards a unified system for expression of biological damage by ionising radiation

International Nuclear Information System (INIS)

Watt, D.E.; Chen, C.Z.; Kadiri, L.; Younis, A.

1987-01-01

Limitations to current systems of radiation dosimetry are discussed. Analyses of a wide range of published data on inactivation of enzymes, viruses, bacteria, plant and mammalian cells by electrons, X and γ-rays, and accelerated ions leads to the conclusion that the main radiosensitive sites in higher cells are the double-stranded segments of DNA. The probability of damage is determined by the mean free path for ionization along the charged particle tracks and is optimum when the spacing matches the mean chord length (2 nm) through a DNA segment. Interpretation of these findings leads to the possibility of a more accurate unified system of dosimetry and to the specification of absolute biological effectiveness. (author)

Lunar Surface Electric Potential Changes Associated with Traversals through the Earth's Foreshock

Science.gov (United States)

Collier, Michael R.; Hills, H. Kent; Stubbs, Timothy J.; Halekas, Jasper S.; Delory, Gregory T.; Espley, Jared; Farrell, William M.; Freeman, John W.; Vondrak, Richard

2011-01-01

We report an analysis of one year of Suprathermal Ion Detector Experiment (SIDE) Total Ion Detector (TID) resonance events observed between January 1972 and January 1973. The study includes only those events during which upstream solar wind conditions were readily available. The analysis shows that these events are associated with lunar traversals through the dawn flank of the terrestrial magnetospheric bow shock. We propose that the events result from an increase in lunar surface electric potential effected by secondary electron emission due to primary electrons in the Earth's foreshock region (although primary ions may play a role as well). This work establishes (1) the lunar surface potential changes as the Moon moves through the terrestrial bow shock, (2) the lunar surface achieves potentials in the upstream foreshock region that differ from those in the downstream magnetosheath region, (3) these differences can be explained by the presence of energetic electron beams in the upstream foreshock region and (4) if this explanation is correct, the location of the Moon with respect to the terrestrial bow shock influences lunar surface potential.

Traversing every edge in each direction once, but not at once: Cubic (polyhedral graphs

Directory of Open Access Journals (Sweden)

Vladimir R. Rosenfeld

2017-04-01

Full Text Available A {\\em retracting-free bidirectional circuit} in a graph $G$ is a closed walk which traverses every edge exactly once in each direction and such that no edge is succeeded by the same edge in the opposite direction. Such a circuit revisits each vertex only in a number of steps. Studying the class $\\mathit{\\Omega}$ of all graphs admitting at least one retracting-free bidirectional circuit was proposed by Ore (1951 and is by now of practical use to nanotechnology. The latter needs in various molecular polyhedra that are constructed from a single chain molecule in the retracting-free way. Some earlier results for simple graphs, obtained by Thomassen and, then, by other authors, are specially refined by us for a cubic graph $Q$. Most of such refinements depend only on the number $n$ of vertices of $Q$.

Spectral shifts of mammalian ultraviolet-sensitive pigments (short wavelength-sensitive opsin 1) are associated with eye length and photic niche evolution.

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Emerling, Christopher A; Huynh, Hieu T; Nguyen, Minh A; Meredith, Robert W; Springer, Mark S

2015-11-22

Retinal opsin photopigments initiate mammalian vision when stimulated by light. Most mammals possess a short wavelength-sensitive opsin 1 (SWS1) pigment that is primarily sensitive to either ultraviolet or violet light, leading to variation in colour perception across species. Despite knowledge of both ultraviolet- and violet-sensitive SWS1 classes in mammals for 25 years, the adaptive significance of this variation has not been subjected to hypothesis testing, resulting in minimal understanding of the basis for mammalian SWS1 spectral tuning evolution. Here, we gathered data on SWS1 for 403 mammal species, including novel SWS1 sequences for 97 species. Ancestral sequence reconstructions suggest that the most recent common ancestor of Theria possessed an ultraviolet SWS1 pigment, and that violet-sensitive pigments evolved at least 12 times in mammalian history. We also observed that ultraviolet pigments, previously considered to be a rarity, are common in mammals. We then used phylogenetic comparative methods to test the hypotheses that the evolution of violet-sensitive SWS1 is associated with increased light exposure, extended longevity and longer eye length. We discovered that diurnal mammals and species with longer eyes are more likely to have violet-sensitive pigments and less likely to possess UV-sensitive pigments. We hypothesize that (i) as mammals evolved larger body sizes, they evolved longer eyes, which limited transmittance of ultraviolet light to the retina due to an increase in Rayleigh scattering, and (ii) as mammals began to invade diurnal temporal niches, they evolved lenses with low UV transmittance to reduce chromatic aberration and/or photo-oxidative damage. © 2015 The Author(s).

Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

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Unniappan, Suraj

2010-07-01

The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

Endogenous retrovirus sequences expressed in male mammalian ...

African Journals Online (AJOL)

Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

Retention of the Native Epigenome in Purified Mammalian Chromatin.

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Andreas H Ehrensberger

Full Text Available A protocol is presented for the isolation of native mammalian chromatin as fibers of 25-250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed.

A role for carbohydrate recognition in mammalian sperm-egg binding

International Nuclear Information System (INIS)

Clark, Gary F.

2014-01-01

Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented

Edible Scaffolds Based on Non-Mammalian Biopolymers for Myoblast Growth

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Javier Enrione

2017-12-01

Full Text Available In vitro meat has recently emerged as a new concept in food biotechnology. Methods to produce in vitro meat generally involve the growth of muscle cells that are cultured on scaffolds using bioreactors. Suitable scaffold design and manufacture are critical to downstream culture and meat production. Most current scaffolds are based on mammalian-derived biomaterials, the use of which is counter to the desire to obviate mammal slaughter in artificial meat production. Consequently, most of the knowledge is related to the design and control of scaffold properties based on these mammalian-sourced materials. To address this, four different scaffold materials were formulated using non-mammalian sources, namely, salmon gelatin, alginate, and additives including gelling agents and plasticizers. The scaffolds were produced using a freeze-drying process, and the physical, mechanical, and biological properties of the scaffolds were evaluated. The most promising scaffolds were produced from salmon gelatin, alginate, agarose, and glycerol, which exhibited relatively large pore sizes (~200 μm diameter and biocompatibility, permitting myoblast cell adhesion (~40% and growth (~24 h duplication time. The biodegradation profiles of the scaffolds were followed, and were observed to be less than 25% after 4 weeks. The scaffolds enabled suitable myogenic response, with high cell proliferation, viability, and adequate cell distribution throughout. This system composed of non-mammalian edible scaffold material and muscle-cells is promising for the production of in vitro meat.

A role for carbohydrate recognition in mammalian sperm-egg binding

Energy Technology Data Exchange (ETDEWEB)

Clark, Gary F., E-mail: clarkgf@health.missouri.edu

2014-08-01

Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the egg cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented.

Overproduction, purification, crystallization and preliminary X-ray diffraction analysis of Cockayne syndrome protein A in complex with DNA damage-binding protein 1

International Nuclear Information System (INIS)

Meulenbroek, Elisabeth M.; Pannu, Navraj S.

2011-01-01

Human Cockayne syndrome protein A has been cocrystallized with human DNA damage-binding protein 1 and data have been collected to 2.9 Å resolution. Cockayne syndrome protein A is one of the main components in mammalian transcription coupled repair. Here, the overproduction, purification and crystallization of human Cockayne syndrome protein A in complex with its interacting partner DNA damage binding protein 1 are reported. The complex was coproduced in insect cells, copurified and crystallized using sitting drops with PEG 3350 and sodium citrate as crystallizing agents. The crystals had unit-cell parameters a = b = 142.03, c = 250.19 Å and diffracted to 2.9 Å resolution on beamline ID14-1 at the European Synchrotron Radiation Facility

Non-ionizing radiofrequency electromagnetic waves traversing the head can be used to detect cerebrovascular autoregulation responses

Science.gov (United States)

Oziel, M.; Hjouj, M.; Gonzalez, C. A.; Lavee, J.; Rubinsky, B.

2016-02-01

Monitoring changes in non-ionizing radiofrequency electromagnetic waves as they traverse the brain can detect the effects of stimuli employed in cerebrovascular autoregulation (CVA) tests on the brain, without contact and in real time. CVA is a physiological phenomenon of importance to health, used for diagnosis of a number of diseases of the brain with a vascular component. The technology described here is being developed for use in diagnosis of injuries and diseases of the brain in rural and economically underdeveloped parts of the world. A group of nine subjects participated in this pilot clinical evaluation of the technology. Substantial research remains to be done on correlating the measurements with physiology and anatomy.

A survey of the sequence-specific interaction of damaging agents with DNA: emphasis on antitumor agents.

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Murray, V

1999-01-01

This article reviews the literature concerning the sequence specificity of DNA-damaging agents. DNA-damaging agents are widely used in cancer chemotherapy. It is important to understand fully the determinants of DNA sequence specificity so that more effective DNA-damaging agents can be developed as antitumor drugs. There are five main methods of DNA sequence specificity analysis: cleavage of end-labeled fragments, linear amplification with Taq DNA polymerase, ligation-mediated polymerase chain reaction (PCR), single-strand ligation PCR, and footprinting. The DNA sequence specificity in purified DNA and in intact mammalian cells is reviewed for several classes of DNA-damaging agent. These include agents that form covalent adducts with DNA, free radical generators, topoisomerase inhibitors, intercalators and minor groove binders, enzymes, and electromagnetic radiation. The main sites of adduct formation are at the N-7 of guanine in the major groove of DNA and the N-3 of adenine in the minor groove, whereas free radical generators abstract hydrogen from the deoxyribose sugar and topoisomerase inhibitors cause enzyme-DNA cross-links to form. Several issues involved in the determination of the DNA sequence specificity are discussed. The future directions of the field, with respect to cancer chemotherapy, are also examined.

Evaluation of the ability of arsenic species to traverse cell membranes by simple diffusion using octanol-water and liposome-water partition coefficients.

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Chávez-Capilla, Teresa; Maher, William; Kelly, Tamsin; Foster, Simon

2016-11-01

Arsenic metabolism in living organisms is dependent on the ability of different arsenic species to traverse biological membranes. Simple diffusion provides an alternative influx and efflux route to mediated transport mechanisms that can increase the amount of arsenic available for metabolism in cells. Using octanol-water and liposome-water partition coefficients, the ability of arsenous acid, arsenate, methylarsonate, dimethylarsinate, thio-methylarsonate, thio-dimethylarsinic acid, arsenotriglutathione and monomethylarsonic diglutathione to diffuse through the lipid bilayer of cell membranes was investigated. Molecular modelling of arsenic species was used to explain the results. All arsenic species with the exception of arsenate, methylarsonate and thio-methylarsonate were able to diffuse through the lipid bilayer of liposomes, with liposome-water partition coefficients between 0.04 and 0.13. Trivalent arsenic species and thio-pentavalent arsenic species showed higher partition coefficients, suggesting that they can easily traverse cell membranes by passive simple diffusion. Given the higher toxicity of these species compared to oxo-pentavalent arsenic species, this study provides evidence supporting the risk associated with human exposure to trivalent and thio-arsenic species. Copyright © 2016. Published by Elsevier B.V.

Risk scaling factors from inactivation to chromosome aberrations, mutations and oncogenic transformations in mammalian cells

International Nuclear Information System (INIS)

Alkaharam, A.S.; Watt, D.E.

1997-01-01

Analyses of bio-effect mechanisms of damage to mammalian cells in terms of the quality parameter 'mean free path for primary ionisation', for heavy charged particles, strongly suggests that there is a common mechanism for the biological endpoints of chromosome aberrations, mutations and oncogenic transformation. The lethal lesions are identified as unrepaired double-strand breaks in the intracellular DNA. As data for the various endpoints studied can be represented in a unified scheme, for any radiation type, it follows that radiation risk factors can be determined on the basis of simple ratios to the inactivation cross sections. There are intrinsic physical reasons why neutrons can never reach the saturation level of heavier particles for equal fluences. The probabilities of risk with respect to inactivation, for chromosome dicentrics, mutation of the HPRT gene and of oncogenic transformation are respectively 0.24, 5.8 x 10 -5 , and 4.1 x 10 -3 . (author)

Radiation damage prediction system using damage function

International Nuclear Information System (INIS)

Tanaka, Yoshihisa; Mori, Seiji

1979-01-01

The irradiation damage analysis system using a damage function was investigated. This irradiation damage analysis system consists of the following three processes, the unfolding of a damage function, the calculation of the neutron flux spectrum of the object of damage analysis and the estimation of irradiation effect of the object of damage analysis. The damage function is calculated by applying the SAND-2 code. The ANISN and DOT3, 5 codes are used to calculate neutron flux. The neutron radiation and the allowable time of reactor operation can be estimated based on these calculations of the damage function and neutron flux. The flow diagram of the process of analyzing irradiation damage by a damage function and the flow diagram of SAND-2 code are presented, and the analytical code for estimating damage, which is determined with a damage function and a neutron spectrum, is explained. The application of the irradiation damage analysis system using a damage function was carried out to the core support structure of a fast breeder reactor for the damage estimation and the uncertainty evaluation. The fundamental analytical conditions and the analytical model for this work are presented, then the irradiation data for SUS304, the initial estimated values of a damage function, the error analysis for a damage function and the analytical results are explained concerning the computation of a damage function for 10% total elongation. Concerning the damage estimation of FBR core support structure, the standard and lower limiting values of damage, the permissible neutron flux and the allowable years of reactor operation are presented and were evaluated. (Nakai, Y.)

Exit angle, energy loss and internuclear distance distributions of H2+ ions dissociated when traversing different materials

International Nuclear Information System (INIS)

Garcia-Molina, Rafael; Abril, Isabel; Denton, Cristian D.; Arista, Nestor R.

2000-01-01

We have performed computer simulations of the trajectory followed by each proton resulting from the dissociation of H 2 + molecules when traversing a thin solid target. We use the dielectric formalism to describe the forces due to electronic excitations in the medium, and we also consider the Coulomb repulsion between the pair of protons. Nuclear collisions with target nuclei are incorporated through a Monte Carlo code and the effect of the coherent scattering is taken into account by means of an effective force model. The distributions of exit angle, energy loss and internuclear separations of the protons fragments are discussed for the case of amorphous carbon and aluminum targets

Variability of {sup 10}Be and {delta}{sup 18}O in snow pits from Greenland and a surface traverse from Antarctica

Energy Technology Data Exchange (ETDEWEB)

Berggren, A.-M. [Dept. of Earth Sciences, Uppsala University, Villav. 16, 752 36 Uppsala (Sweden); Aldahan, A., E-mail: ala.aldahan@geo.uu.se [Dept. of Earth Sciences, Uppsala University, Villav. 16, 752 36 Uppsala (Sweden); Dept. of Geology, United Arab Emirates University, P.O. Box 17551 Al Ain (United Arab Emirates); Possnert, G. [Tandem Laboratory, Uppsala University, P.O. Box 529, 751 20 Uppsala (Sweden); Hansson, M. [Dept. of Physical Geography and Quaternary Geology, Stockholm University, 106 91 Stockholm (Sweden); Steen-Larsen, H.C. [Centre for Ice and Climate, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej, 30,2100 Copenhagen (Denmark); Sturevik Storm, A. [Dept. of Earth Sciences, Uppsala University, Villav. 16, 752 36 Uppsala (Sweden); Moerth, C.-M. [Dept. of Geology and Geochemistry, Stockholm University, 106 91 Stockholm (Sweden); Murad, A. [Dept. of Geology, United Arab Emirates University, P.O. Box 17551 Al Ain (United Arab Emirates)

2013-01-15

To examine temporal variability of {sup 10}Be in glacial ice, we sampled snow to a depth of 160 cm at the NEEM (North Greenland Eemian Ice Drilling) drilling site in Greenland. The samples span three years between the summers of 2006 and 2009. At the same time, spatial variability of {sup 10}Be in glacial ice was explored through collection of the upper {approx}5 cm of surface snow in Antarctica during part of the Swedish-Japanese traverse from Svea to Syowa station during the austral summer in 2007-2008. The results of the Greenlandic {sup 10}Be snow suggested variable concentrations that apparently do not clearly reflect the seasonal change as indicated by the {delta}{sup 18}O data. The {sup 10}Be concentration variability most likely reflects also effects of aerosol loading and deposition pathways, possibly in combination with post-depositional processes. The Antarctic traverse data expose a negative correlation between {sup 10}Be and {delta}{sup 18}O, while there are weaker but still significant correlations to altitude and distance to the coast (approximated by the distance to the 70th latitude). These relationships indicate that geographical factors, mainly the proximity to the coast, may strongly affect {sup 10}Be concentrations in snow in Queen Maud Land, Antarctica.

Effects of mode profile on tunneling and traversal of ultracold atoms through vacuum-induced potentials

Science.gov (United States)

Badshah, Fazal; Irfan, Muhammad; Qamar, Sajid; Qamar, Shahid

2016-04-01

We consider the resonant interaction of an ultracold two-level atom with an electromagnetic field inside a high-Q micromaser cavity. In particular, we study the tunneling and traversal of ultracold atoms through vacuum-induced potentials for secant hyperbolic square and sinusoidal cavity mode functions. The phase time which may be considered as an appropriate measure of the time required for the atoms to cross the cavity, significantly modifies with the change of cavity mode profile. For example, switching between the sub and superclassical behaviors in phase time can occur due to the mode function. Similarly, negative phase time appears for the transmission of the two-level atoms in both excited and ground states for secant hyperbolic square mode function which is in contrast to the mesa mode case.

Mammalian Synthetic Biology: Time for Big MACs.

Science.gov (United States)

Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

2016-10-21

The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

Traversal of cells by radiation and absorbed fraction estimates for electrons and alpha particles

International Nuclear Information System (INIS)

Eckerman, K.F.; Ryman, J.C.; Taner, A.C.; Kerr, G.D.

1986-01-01

Consideration of the pathlength which radiation traverses in a cell is central to algorithms for estimating energy deposition on a cellular level. Distinct pathlength distributions occur for radionuclides: (1) uniformly distributed in space about the cell (referred to as μ-randomness); (2) uniformly distributed on the surface of the cell (S-randomness); and (3) uniformly distributed within the cell volume (I-randomness). For a spherical cell of diameter d, the mean pathlengths are 2/3d, and 3/4d, respectively, for these distributions. Algorithms for simulating the path of radiation through a cell are presented and the absorbed fraction in the cell and its nucleus are tabulated for low energy electrons and alpha particles emitted on the surface of spherical cells. The algorithms and absorbed fraction data should be of interest to those concerned with the dosimetry of radionuclide-labeled monoclonal antibodies. 8 references, 3 figures, 2 tables

Secondary osteons scale allometrically in mammalian humerus and femur.

Science.gov (United States)

Felder, A A; Phillips, C; Cornish, H; Cooke, M; Hutchinson, J R; Doube, M

2017-11-01

Intra-cortical bone remodelling is a cell-driven process that replaces existing bone tissue with new bone tissue in the bone cortex, leaving behind histological features called secondary osteons. While the scaling of bone dimensions on a macroscopic scale is well known, less is known about how the spatial dimensions of secondary osteons vary in relation to the adult body size of the species. We measured the cross-sectional area of individual intact secondary osteons and their central Haversian canals in transverse sections from 40 stylopodal bones of 39 mammalian species (body mass 0.3-21 000 kg). Scaling analysis of our data shows that mean osteonal resorption area (negative allometry, exponent 0.23, R 2  0.54, p <0.005) and Haversian canal area (negative allometry, exponent 0.31, R 2  0.45, p <0.005) are significantly related to body mass, independent of phylogeny. This study is the most comprehensive of its kind to date, and allows us to describe overall trends in the scaling behaviour of secondary osteon dimensions, supporting the inference that the osteonal resorption area may be limited by the need to avoid fracture in smaller mammalian species, but the need to maintain osteocyte viability in larger mammalian species.

Enamel formation and growth in non-mammalian cynodonts

Science.gov (United States)

Dirks, Wendy; Martinelli, Agustín G.

2018-01-01

The early evolution of mammals is associated with the linked evolutionary origin of diphyodont tooth replacement, rapid juvenile growth and determinate adult growth. However, specific relationships among these characters during non-mammalian cynodont evolution require further exploration. Here, polarized light microscopy revealed incremental lines, resembling daily laminations of extant mammals, in histological sections of enamel in eight non-mammalian cynodont species. In the more basal non-probainognathian group, enamel extends extremely rapidly from cusp to cervix. By contrast, the enamel of mammaliamorphs is gradually accreted, with slow rates of crown extension, more typical of the majority of non-hypsodont crown mammals. These results are consistent with the reduction in dental replacement rate across the non-mammalian cynodont lineage, with greater rates of crown extension required in most non-probainognathians, and slower crown extension rates permitted in mammaliamorphs, which have reduced patterns of dental replacement in comparison with many non-probainognathians. The evolution of mammal-like growth patterns, with faster juvenile growth and more abruptly terminating adult growth, is linked with this reduction in dental replacement rates and may provide an additional explanation for the observed pattern in enamel growth rates. It is possible that the reduction in enamel extension rates in mammaliamorphs reflects an underlying reduction in skeletal growth rates at the time of postcanine formation, due to a more abruptly terminating pattern of adult growth in these more mammal-like, crownward species. PMID:29892415

An obligatory role of mind bomb-1 in notch signaling of mammalian development.

Directory of Open Access Journals (Sweden)

Bon-Kyoung Koo

2007-11-01

Full Text Available The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood.Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2(-/- mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants.Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

International Nuclear Information System (INIS)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-01-01

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of γ-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of γ-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced γ-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

Energy Technology Data Exchange (ETDEWEB)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-11-27

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of {gamma}-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of {gamma}-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced {gamma}-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression.

Induced recovery from near- and far-UV damage in cultured marsupial cells

International Nuclear Information System (INIS)

Hoy, D.A.

1982-01-01

Colony-forming ability of cultured rat kangaroo cells (Ptk-2) decreases with increasing exposure to light from a daylight fluorescent lamp. After reaching a minimum, survival increases with further exposure, forming a V-shaped survival curve. This increase is inhibited by low concentrations of the protein synthesis inhibitor cycloheximide. The resulting V-shaped survival curve was characterized with respect to several experimental parameters; it appears to be due to an induced repair system dependent on protein synthesis. These results suggest that induced repair, dependent on protein synthesis, in response to fluorescent, near UV, and far UV light damage, is a major repair pathway in Ptk-2 cells, and provides a characterizable system that can elucidate induced repair mechanisms in other mammalian cells

Self-Supervised Learning of Terrain Traversability from Proprioceptive Sensors

Science.gov (United States)

Bajracharya, Max; Howard, Andrew B.; Matthies, Larry H.

2009-01-01

Robust and reliable autonomous navigation in unstructured, off-road terrain is a critical element in making unmanned ground vehicles a reality. Existing approaches tend to rely on evaluating the traversability of terrain based on fixed parameters obtained via testing in specific environments. This results in a system that handles the terrain well that it trained in, but is unable to process terrain outside its test parameters. An adaptive system does not take the place of training, but supplements it. Whereas training imprints certain environments, an adaptive system would imprint terrain elements and the interactions amongst them, and allow the vehicle to build a map of local elements using proprioceptive sensors. Such sensors can include velocity, wheel slippage, bumper hits, and accelerometers. Data obtained by the sensors can be compared to observations from ranging sensors such as cameras and LADAR (laser detection and ranging) in order to adapt to any kind of terrain. In this way, it could sample its surroundings not only to create a map of clear space, but also of what kind of space it is and its composition. By having a set of building blocks consisting of terrain features, a vehicle can adapt to terrain that it has never seen before, and thus be robust to a changing environment. New observations could be added to its library, enabling it to infer terrain types that it wasn't trained on. This would be very useful in alien environments, where many of the physical features are known, but some are not. For example, a seemingly flat, hard plain could actually be soft sand, and the vehicle would sense the sand and avoid it automatically.

Steroid hydroxylations: A paradigm for cytochrome P450 catalyzed mammalian monooxygenation reactions

International Nuclear Information System (INIS)

Estabrook, Ronald W.

2005-01-01

The present article reviews the history of research on the hydroxylation of steroid hormones as catalyzed by enzymes present in mammalian tissues. The report describes how studies of steroid hormone synthesis have played a central role in the discovery of the monooxygenase functions of the cytochrome P450s. Studies of steroid hydroxylation reactions can be credited with showing that: (a) the adrenal mitochondrial enzyme catalyzing the 11β-hydroxylation of deoxycorticosterone was the first mammalian enzyme shown by O 18 studies to be an oxygenase; (b) the adrenal microsomal enzyme catalyzing the 21-hydroxylation of steroids was the first mammalian enzyme to show experimentally the proposed 1:1:1 stoichiometry (substrate:oxygen:reduced pyridine nucleotide) of a monooxygenase reaction; (c) application of the photochemical action spectrum technique for reversal of carbon monoxide inhibition of the 21-hydroxylation of 17α-OH progesterone was the first demonstration that cytochrome P450 was an oxygenase; (d) spectrophotometric studies of the binding of 17α-OH progesterone to bovine adrenal microsomal P450 revealed the first step in the cyclic reaction scheme of P450, as it catalyzes the 'activation' of oxygen in a monooxygenase reaction; (e) purified adrenodoxin was shown to function as an electron transport component of the adrenal mitochondrial monooxygenase system required for the activity of the 11β-hydroxylase reaction. Adrenodoxin was the first iron-sulfur protein isolated and purified from mammalian tissues and the first soluble protein identified as a reductase of a P450; (f) fractionation of adrenal mitochondrial P450 and incubation with adrenodoxin and a cytosolic (flavoprotein) fraction were the first demonstration of the reconstitution of a mammalian P450 monooxygenase reaction

Molecular Markers for Interspecies Transmission of Avian Influenza Viruses in Mammalian Hosts

Science.gov (United States)

Lee, Taehyung

2017-01-01

In the last decade, a wide range of avian influenza viruses (AIVs) have infected various mammalian hosts and continuously threaten both human and animal health. It is a result of overcoming the inter-species barrier which is mostly associated with gene reassortment and accumulation of mutations in their gene segments. Several recent studies have shed insights into the phenotypic and genetic changes that are involved in the interspecies transmission of AIVs. These studies have a major focus on transmission from avian to mammalian species due to the high zoonotic potential of the viruses. As more mammalian species have been infected with these viruses, there is higher risk of genetic evolution of these viruses that may lead to the next human pandemic which represents and raises public health concern. Thus, understanding the mechanism of interspecies transmission and molecular determinants through which the emerging AIVs can acquire the ability to transmit to humans and other mammals is an important key in evaluating the potential risk caused by AIVs among humans. Here, we summarize previous and recent studies on molecular markers that are specifically involved in the transmission of avian-derived influenza viruses to various mammalian hosts including humans, pigs, horses, dogs, and marine mammals. PMID:29236050

Leadership in Mammalian Societies: Emergence, Distribution, Power, and Payoff.

Science.gov (United States)

Smith, Jennifer E; Gavrilets, Sergey; Mulder, Monique Borgerhoff; Hooper, Paul L; Mouden, Claire El; Nettle, Daniel; Hauert, Christoph; Hill, Kim; Perry, Susan; Pusey, Anne E; van Vugt, Mark; Smith, Eric Alden

2016-01-01

Leadership is an active area of research in both the biological and social sciences. This review provides a transdisciplinary synthesis of biological and social-science views of leadership from an evolutionary perspective, and examines patterns of leadership in a set of small-scale human and non-human mammalian societies. We review empirical and theoretical work on leadership in four domains: movement, food acquisition, within-group conflict mediation, and between-group interactions. We categorize patterns of variation in leadership in five dimensions: distribution (across individuals), emergence (achieved versus inherited), power, relative payoff to leadership, and generality (across domains). We find that human leadership exhibits commonalities with and differences from the broader mammalian pattern, raising interesting theoretical and empirical issues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of lipid peroxidation and protein oxidation biomarkers for oxidative damage in mammalian cells. A comparison with two fluorescent probes

NARCIS (Netherlands)

Orhan, H.; Gurer-Orhan, H.; Vriese, E.; Vermeulen, N.P.E.; Meerman, J.H.N.

2006-01-01

We recently developed two biomarker sets for oxidative damage: one for determination of lipid peroxidation (LPO) degradation products; acetaldehyde, propanal, butanal, pentanal, hexanal, heptanal, octanal, nonanal, malondialdehyde and acetone, by a gas chromatography-electron capture detection

E-type cyclins modulate telomere integrity in mammalian male meiosis.

Science.gov (United States)

Manterola, Marcia; Sicinski, Piotr; Wolgemuth, Debra J

2016-06-01

We have shown that E-type cyclins are key regulators of mammalian male meiosis. Depletion of cyclin E2 reduced fertility in male mice due to meiotic defects, involving abnormal pairing and synapsis, unrepaired DNA, and loss of telomere structure. These defects were exacerbated by additional loss of cyclin E1, and complete absence of both E-type cyclins produces a meiotic catastrophe. Here, we investigated the involvement of E-type cyclins in maintaining telomere integrity in male meiosis. Spermatocytes lacking cyclin E2 and one E1 allele (E1+/-E2-/-) displayed a high rate of telomere abnormalities but can progress to pachytene and diplotene stages. We show that their telomeres exhibited an aberrant DNA damage repair response during pachynema and that the shelterin complex proteins TRF2 and RAP2 were significantly decreased in the proximal telomeres. Moreover, the insufficient level of these proteins correlated with an increase of γ-H2AX foci in the affected telomeres and resulted in telomere associations involving TRF1 and telomere detachment in later prophase-I stages. These results suggest that E-type cyclins are key modulators of telomere integrity during meiosis by, at least in part, maintaining the balance of shelterin complex proteins, and uncover a novel role of E-type cyclins in regulating chromosome structure during male meiosis.

Method for detecting DNA strand breaks in mammalian cells using the Deinococcus radiodurans PprA protein

International Nuclear Information System (INIS)

Satoh, Katsuya; Wada, Seiichi; Kikuchi, Masahiro; Funayama, Tomoo; Narumi, Issay; Kobayashi, Yasuhiko

2006-01-01

In a previous study, we identified the novel protein PprA that plays a critical role in the radiation resistance of Deinococcus radiodurans. In this study, we focussed on the ability of PprA protein to recognize and bind to double-stranded DNA carrying strand breaks, and attempted to visualize radiation-induced DNA strand breaks in mammalian cultured cells by employing PprA protein using an immunofluorescence technique. Increased PprA protein binding to CHO-K1 nuclei immediately following irradiation suggests the protein is binding to DNA strand breaks. By altering the cell permeabilization conditions, PprA protein binding to CHO-K1 mitochondria, which is probably resulted from DNA strand break immediately following irradiation, was also detected. The method developed and detailed in this study will be useful in evaluating DNA damage responses in cultured cells, and could also be applicable to genotoxic tests in the environmental and pharmaceutical fields

Fossilized Mammalian Erythrocytes Associated With a Tick Reveal Ancient Piroplasms.

Science.gov (United States)

Poinar, George

2017-07-01

Ticks transmit a variety of pathogenic organisms to vertebrates, especially mammals. The fossil record of such associations is extremely rare. An engorged nymphal tick of the genus Ambylomma in Dominican amber was surrounded by erythrocytes from its mammalian host. Some of the exposed erythrocytes contained developmental stages of a hemoprotozoan resembling members of the Order Piroplasmida. The fossil piroplasm is described, its stages compared with those of extant piroplasms, and reasons provided why the mammalian host could have been a primate. The parasites were also found in the gut epithelial cells and body cavity of the fossil tick. Aside from providing the first fossil mammalian red blood cells and the first fossil intraerythrocytic hemoparasites, the present discovery shows that tick-piroplasm associations were already well established in the Tertiary. This discovery provides a timescale that can be used in future studies on the evolution of the Piroplasmida. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com Version of Record, first published online March 20, 2017 with fixed content and layout in compliance with Art. 8.1.3.2 ICZN.

Optical sorting and photo-transfection of mammalian cells

CSIR Research Space (South Africa)

Mthunzi, P

2010-02-01

Full Text Available and that the scattering force can enable sorting through axial guiding onto laminin coated glass coverslips upon which the selected cells adhere. Following this, I report on transient photo-transfection of mammalian cells including neuroblastomas (rat/mouse and human...

Landing Site Selection and Surface Traverse Planning using the Lunar Mapping & Modeling Portal

Science.gov (United States)

Law, E.; Chang, G.; Bui, B.; Sadaqathullah, S.; Kim, R.; Dodge, K.; Malhotra, S.

2013-12-01

Introduction: The Lunar Mapping and Modeling Portal (LMMP), is a web-based Portal and a suite of interactive visualization and analysis tools for users to access mapped lunar data products (including image mosaics, digital elevation models, etc.) from past and current lunar missions (e.g., Lunar Reconnaissance Orbiter, Apollo, etc.), and to perform in-depth analyses to support lunar surface mission planning and system design for future lunar exploration and science missions. It has been widely used by many scientists mission planners, as well as educators and public outreach (e.g., Google Lunar XPRICE teams, RESOLVE project, museums etc.) This year, LMMP was used by the Lunar and Planetary Institute (LPI)'s Lunar Exploration internship program to perform lighting analysis and local hazard assessments, such as, slope, surface roughness and crater/boulder distribution to research landing sites and surface pathfinding and traversal. Our talk will include an overview of LMMP, a demonstration of the tools as well as a summary of the LPI Lunar Exploration summer interns' experience in using those tools.

A New MANET Wormhole Detection Algorithm Based on Traversal Time and Hop Count Analysis

Directory of Open Access Journals (Sweden)

Göran Pulkkis

2011-11-01

Full Text Available As demand increases for ubiquitous network facilities, infrastructure-less and self-configuring systems like Mobile Ad hoc Networks (MANET are gaining popularity. MANET routing security however, is one of the most significant challenges to wide scale adoption, with wormhole attacks being an especially severe MANET routing threat. This is because wormholes are able to disrupt a major component of network traffic, while concomitantly being extremely difficult to detect. This paper introduces a new wormhole detection paradigm based upon Traversal Time and Hop Count Analysis (TTHCA, which in comparison to existing algorithms, consistently affords superior detection performance, allied with low false positive rates for all wormhole variants. Simulation results confirm that the TTHCA model exhibits robust wormhole route detection in various network scenarios, while incurring only a small network overhead. This feature makes TTHCA an attractive choice for MANET environments which generally comprise devices, such as wireless sensors, which possess a limited processing capability.

Traversal of cells by radiation and absorbed fraction estimates for electrons and alpha particles

International Nuclear Information System (INIS)

Eckerman, K.F.; Ryman, J.C.; Taner, A.C.; Kerr, G.D.

1985-01-01

Consideration of the pathlength which radiation traverses in a cell is central to algorithms for estimating energy deposition on a cellular level. Distinct pathlength distributions occur for radionuclides: (1) uniformly distributed in space about the cell (referred to as μ-randomness); (2) uniformly distributed on the surface of the cell (S-randomness); and (3) uniformly distributed within the cell volume (I-randomness). For a spherical cell of diameter d, the mean pathlengths are 2/3d, 1/2d, and 3/4d, respectively, for these distributions. Algorithms for simulating the path of radiation through a cell are presented and the absorbed fraction in the cell and its nucleus are tabulated for low energy electrons and alpha particles emitted on the surface of spherical cells. The algorithms and absorbed fraction data should be of interest to those concerned with the dosimetry of radionuclide-labeled monoclonal antibodies. 8 refs., 3 figs., 2 tabs

Metabolite Damage and Metabolite Damage Control in Plants

Energy Technology Data Exchange (ETDEWEB)

Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

2016-04-29

It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

International Nuclear Information System (INIS)

Gehrau, Ricardo C.; D'Astolfo, Diego S.; Andreoli, Veronica; Bocco, Jose L.; Koritschoner, Nicolas P.

2011-01-01

The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC 50 ). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p 50 concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable marker for the efficiency of cell death upon cancer treatment.

Mammalian target of rapamycin activity is required for expansion of CD34(+) hematopoietic progenitor cells

NARCIS (Netherlands)

Geest, Christian R.; Zwartkruis, Fried J.; Vellenga, Edo; Coffer, Paul J.; Buitenhuis, Miranda

Background The mammalian target of rapamycin is a conserved protein kinase known to regulate protein synthesis, cell size and proliferation. Aberrant regulation of mammalian target of rapamycin activity has been observed in hematopoietic malignancies, including acute leukemias and myelodysplastic

Production and excision of thymine damage in the DNA of mammalian cells exposed to high-LET radiations

International Nuclear Information System (INIS)

Mattern, M.R.; Welch, G.P.

1979-01-01

HeLa S3 and Chinese hamster ovary cells were irradiated with high doses of carbon ions having linear energy transfers (LETs) of 170 and 780 keV/μm. The DNA was analyzed for 5,6-dihydroxydihydrothymine (t'-type) radiation products both before and after postirradiation incubation at 37 0 C. In HeLa cells, 2.1 x 10 -5 ring-damaged thymines were produced per kilorad per 10 6 daltons after irradiation with high-LET carbon ions - approximately one-fifth the efficiency of t' formation in HeLa cells exposed to low-LET x rays. t' products were also formed less efficiently in Chinese hamster ovary cells exposed to carbon ions than in those exposed to x rays. In both cell lines, up to 80% of the t' formed initially was excised selectively from the DNA during 60 min of postirradiation incubation at 37 0 C. Product excision was accompanied by small amounts of DNA degradation (less than 1%). Radiation with LET of 170 keV/μm - nearly the most effective LET for cell killing and the generation of unrejoined DNA strand breaks - produced ring-damaged thymines that were removed selectively from the DNA. This result is consistent with the conclusion that t'-type products do not contribute substantially to lethality after high-LET irradiation, although the alternative possibilities remain that t' is not excised as efficiently after biological doses, or that a particular subclass of t' or defective postexcision events contribute to cell killing

The evolution of gene expression levels in mammalian organs

DEFF Research Database (Denmark)

Brawand, David; Soumillon, Magali; Necsulea, Anamaria

2011-01-01

and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped......Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across...... ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages...

A Flexure-Guided Piezo Drill for Penetrating the Zona Pellucida of Mammalian Oocytes.

Science.gov (United States)

Johnson, Wesley; Dai, Changsheng; Liu, Jun; Wang, Xian; Luu, Devin K; Zhang, Zhuoran; Ru, Changhai; Zhou, Chao; Tan, Min; Pu, Huayan; Xie, Shaorong; Peng, Yan; Luo, Jun; Sun, Yu

2018-03-01

Mammalian oocytes such as mouse oocytes have a highly elastic outer membrane, zona pellucida (ZP) that cannot be penetrated without significantly deforming the oocyte, even with a sharp micropipette. Piezo drill devices leverage lateral and axial vibration of the micropipette to accomplish ZP penetration with greatly reduced oocyte deformation. However, existing piezo drills all rely on a large lateral micropipette vibration amplitude ( 20 ) and a small axial vibration amplitude (0.1 ). The very large lateral vibration amplitude has been deemed to be necessary for ZP penetration although it also induces larger oocyte deformation and more oocyte damage. This paper reports on a new piezo drill device that uses a flexure guidance mechanism and a systematically designed pulse train with an appropriate base frequency. Both simulation and experimental results demonstrate that a small lateral vibration amplitude (e.g., 2 ) and an axial vibration amplitude as large as 1.2 were achieved. Besides achieving 100% effectiveness in the penetration of mouse oocytes (n = 45), the new piezo device during ZP penetration induced a small oocyte deformation of 3.4 versus larger than 10 using existing piezo drill devices.

Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

Science.gov (United States)

2014-01-01

The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, in Saccharomyces cerevisiae, haploid strains defective in the TEL1 gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development. PMID:25247188

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

Science.gov (United States)

Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

2018-02-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

Science.gov (United States)

Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

2018-01-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

Measurement of Heme Synthesis Levels in Mammalian Cells.

Science.gov (United States)

Hooda, Jagmohan; Alam, Maksudul; Zhang, Li

2015-07-09

Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5-aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines.

Genetic Analysis of a Mammalian Chromosomal Origin of Replication

National Research Council Canada - National Science Library

Altman, Amy

2001-01-01

The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

A case study of the intraseasonal oscillation traversing the TOGA-COARE LSD. [large-scale domain

Science.gov (United States)

Vincent, Dayton G.; Schrage, Jon M.; Sliwinski, L. D.

1993-01-01

The paper presents examination of tree intraseasonal (30-60 day) oscillations (ISOs) that occurred during the southern summer season (December 1, 1985 - February 28, 1986) traversing the Large-Scale Domain (LSD) TOGA-COARE, the region which also plays an important role in ENSO, Australian monsoon, and extratropical circulations. Data presented include Hovmoeller diagrams of 5-day running means of 250-mb velocity potential anomalies and OLR anomalies; graphs of five-day running means of OLR in precipitable water (W) per sq m, averaged over 10 x 10 deg boxes centered on 5 S and (1) 145 E, (2) 155 E, (3) 165 E, and (4) 165 D, indicating the midpoint of each ISO; and vertical profiles of zonal wind in m/s averaged over the time period that each ISO spends in the 10 x 10 deg box centered at 5 S, and 175 E and 145 E.

Algal autolysate medium to label proteins for NMR in mammalian cells.

Science.gov (United States)

Fuccio, Carmelo; Luchinat, Enrico; Barbieri, Letizia; Neri, Sara; Fragai, Marco

2016-04-01

In-cell NMR provides structural and functional information on proteins directly inside living cells. At present, the high costs of the labeled media for mammalian cells represent a limiting factor for the development of this methodology. Here we report a protocol to prepare a homemade growth medium from Spirulina platensis autolysate, suitable to express uniformly labeled proteins inside mammalian cells at a reduced cost-per-sample. The human proteins SOD1 and Mia40 were overexpressed in human cells grown in (15)N-enriched S. platensis algal-derived medium, and high quality in-cell NMR spectra were obtained.

Algal autolysate medium to label proteins for NMR in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Fuccio, Carmelo; Luchinat, Enrico; Barbieri, Letizia [University of Florence, Magnetic Resonance Center (CERM) (Italy); Neri, Sara [Giotto Biotech S.R.L. (Italy); Fragai, Marco, E-mail: fragai@cerm.unifi.it [University of Florence, Magnetic Resonance Center (CERM) (Italy)

2016-04-15

In-cell NMR provides structural and functional information on proteins directly inside living cells. At present, the high costs of the labeled media for mammalian cells represent a limiting factor for the development of this methodology. Here we report a protocol to prepare a homemade growth medium from Spirulina platensis autolysate, suitable to express uniformly labeled proteins inside mammalian cells at a reduced cost-per-sample. The human proteins SOD1 and Mia40 were overexpressed in human cells grown in {sup 15}N-enriched S. platensis algal-derived medium, and high quality in-cell NMR spectra were obtained.

Electroporation of Mammalian Cells by Nanosecond Electric Field Oscillations and its Inhibition by the Electric Field Reversal

Science.gov (United States)

2015-09-08

Report 3. DATES COVERED (From – To) March 2013 to July 2015 4. TITLE AND SUBTITLE Electroporation of mammalian cells by nanosecond electric field...Prescribed by ANSI Std. Z39.18 1Scientific RepoRts | 5:13818 | DOi: 10.1038/srep13818 www.nature.com/scientificreports Electroporation of mammalian cells...first to demonstrate that mammalian cells can be electroporated by damped sine wave electric stimuli of nanosecond duration. By comparing the

Paired Chicken and Mammalian Erythrocyte Indicator Systems for ...

African Journals Online (AJOL)

Three levels of erythrocytes suspensions, 1.5%, 1% and 0.5% respectively from goat and guinea pig, were compared to conventional 0.5% chicken erythrocytes, in an attempt to investigate the suitability for the two sources of mammalian erythrocytes as indicators for Newcastle disease virus haemagglutination (HA) tests.

Mammalian amyloidogenic proteins promote prion nucleation in yeast.

Science.gov (United States)

Chandramowlishwaran, Pavithra; Sun, Meng; Casey, Kristin L; Romanyuk, Andrey V; Grizel, Anastasiya V; Sopova, Julia V; Rubel, Aleksandr A; Nussbaum-Krammer, Carmen; Vorberg, Ina M; Chernoff, Yury O

2018-03-02

Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and the expression of a mammalian amyloidogenic protein that is not fused to the Sup35 prion domain failed to promote prion nucleation, further indicating that physical linkage of a mammalian amyloidogenic protein to the prion domain of a yeast protein is required for the nucleation of a yeast prion. Biochemical and cytological approaches confirmed the nucleation of protein aggregates in the yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of human amyloid-β (associated with Alzheimer's disease) and mouse prion protein (associated with prion diseases), respectively, antagonized or enhanced nucleation of a yeast prion by these proteins. The yeast-based prion nucleation assay, developed in our work, can be employed for mutational dissection of amyloidogenic proteins. We anticipate that it will aid in the identification of chemicals that influence initial amyloid nucleation and in searching for new amyloidogenic proteins in a variety of proteomes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Science.gov (United States)

Levine, Zebulon G; Walker, Suzanne

2016-06-02

O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

Chlorophacinone residues in mammalian prey at a black-tailed prairie dog colony

Science.gov (United States)

Vyas, Nimish B.; Hulse, Craig S.; Rice, Clifford P.

2012-01-01

Black-tailed prairie dogs (BTPDs), Cynomys ludovicianus, are an important prey for raptors; therefore, the use of the rodenticide Rozol (0.005% chlorophacinone active ingredient) to control BTPDs raises concern for secondary poisonings resulting from the consumption of contaminated prey by raptors. In the present study, the authors observed Rozol exposure and adverse effects to mammalian prey on 11 of 12 search days of the study. Mammalian hepatic chlorophacinone residues ranged from 0.44 to 7.56 µg/g. Poisoned prey availability was greater than previously reported.

Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake.

Directory of Open Access Journals (Sweden)

Lieming Bao

Full Text Available Polychlorinated biphenyls (PCBs are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs using the mammalian pregnane X receptor (PXR. In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL-PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants.

The metabolic and ecological interactions of oxalate-degrading bacteria in the Mammalian gut.

Science.gov (United States)

Miller, Aaron W; Dearing, Denise

2013-12-06

Oxalate-degrading bacteria comprise a functional group of microorganisms, commonly found in the gastrointestinal tract of mammals. Oxalate is a plant secondary compound (PSC) widely produced by all major taxa of plants and as a terminal metabolite by the mammalian liver. As a toxin, oxalate can have a significant impact on the health of mammals, including humans. Mammals do not have the enzymes required to metabolize oxalate and rely on their gut microbiota for this function. Thus, significant metabolic interactions between the mammalian host and a complex gut microbiota maintain the balance of oxalate in the body. Over a dozen species of gut bacteria are now known to degrade oxalate. This review focuses on the host-microbe and microbe-microbe interactions that regulate the degradation of oxalate by the gut microbiota. We discuss the pathways of oxalate throughout the body and the mammalian gut as a series of differentiated ecosystems that facilitate oxalate degradation. We also explore the mechanisms and functions of microbial oxalate degradation along with the implications for the ecological and evolutionary interactions within the microbiota and for mammalian hosts. Throughout, we consider questions that remain, as well as recent technological advances that can be employed to answer them.

Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage

Science.gov (United States)

Klungland, Arne; Rosewell, Ian; Hollenbach, Stephan; Larsen, Elisabeth; Daly, Graham; Epe, Bernd; Seeberg, Erling; Lindahl, Tomas; Barnes, Deborah E.

1999-01-01

DNA damage generated by oxidant byproducts of cellular metabolism has been proposed as a key factor in cancer and aging. Oxygen free radicals cause predominantly base damage in DNA, and the most frequent mutagenic base lesion is 7,8-dihydro-8-oxoguanine (8-oxoG). This altered base can pair with A as well as C residues, leading to a greatly increased frequency of spontaneous G·C→T·A transversion mutations in repair-deficient bacterial and yeast cells. Eukaryotic cells use a specific DNA glycosylase, the product of the OGG1 gene, to excise 8-oxoG from DNA. To assess the role of the mammalian enzyme in repair of DNA damage and prevention of carcinogenesis, we have generated homozygous ogg1−/− null mice. These animals are viable but accumulate abnormal levels of 8-oxoG in their genomes. Despite this increase in potentially miscoding DNA lesions, OGG1-deficient mice exhibit only a moderately, but significantly, elevated spontaneous mutation rate in nonproliferative tissues, do not develop malignancies, and show no marked pathological changes. Extracts of ogg1 null mouse tissues cannot excise the damaged base, but there is significant slow removal in vivo from proliferating cells. These findings suggest that in the absence of the DNA glycosylase, and in apparent contrast to bacterial and yeast cells, an alternative repair pathway functions to minimize the effects of an increased load of 8-oxoG in the genome and maintain a low endogenous mutation frequency. PMID:10557315

Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family.

Science.gov (United States)

Wilson-O'Brien, Amy L; Patron, Nicola; Rogers, Suzanne

2010-05-21

In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

Mammalian sleep dynamics: how diverse features arise from a common physiological framework.

Directory of Open Access Journals (Sweden)

Andrew J K Phillips

2010-06-01

Full Text Available Mammalian sleep varies widely, ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans. In humans, rats, mice and cats, sleep patterns are orchestrated by homeostatic and circadian drives to the sleep-wake switch, but it is not known whether this system is ubiquitous among mammals. Here, changes of just two parameters in a recent quantitative model of this switch are shown to reproduce typical sleep patterns for 17 species across 7 orders. Furthermore, the parameter variations are found to be consistent with the assumptions that homeostatic production and clearance scale as brain volume and surface area, respectively. Modeling an additional inhibitory connection between sleep-active neuronal populations on opposite sides of the brain generates unihemispheric sleep, providing a testable hypothetical mechanism for this poorly understood phenomenon. Neuromodulation of this connection alone is shown to account for the ability of fur seals to transition between bihemispheric sleep on land and unihemispheric sleep in water. Determining what aspects of mammalian sleep patterns can be explained within a single framework, and are thus universal, is essential to understanding the evolution and function of mammalian sleep. This is the first demonstration of a single model reproducing sleep patterns for multiple different species. These wide-ranging findings suggest that the core physiological mechanisms controlling sleep are common to many mammalian orders, with slight evolutionary modifications accounting for interspecies differences.

Mammalian cell biology

International Nuclear Information System (INIS)

Anon.

1976-01-01

Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

Mammalian Gut Immunity

Science.gov (United States)

Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

2016-01-01

The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

Pervasive aeolian activity along Curiosity's traverse in Gale Crater on Mars

Science.gov (United States)

Silvestro, S.; Vaz, D.; Ewing, R. C.; Rossi, A.; Flahaut, J.; Fenton, L. K.; Geissler, P. E.; Michaels, T. I.

2012-12-01

The NASA Mars Science Laboratory (MSL) has safely landed in Gale Crater (Mars). This crater has been severely modified by the action of the wind which has led to the development of several dark dune fields. One of these fields crosses the landing ellipse from the NE to the SW, and despite its fresh appearance, no evidence of sand movement has been detected until recently. Here we present evidence of current aeolian activity in the form of ripple and dune migration close to the expected traverse of the MSL rover, Curiosity. We calculate a minimum ripple displacement of 1.16 m and a dune migration rate of 0.4 meters/Earth year. Both ripples and dunes migrated toward the SW, suggesting winds above the saltation threshold from the NE. Such winds are predicted by the MRAMS atmospheric model (Fig. 1). The dunes are undergoing changes on a timescale of weeks to a few years that should be detectable by rover instruments. Using theoretical and experimental considerations, we calculate a wind gust velocity of 35 m/s at 1.5 m of height. In addition, we estimate that saltating grains would reach a distance of ~27 m and extend a maximum height of 2 m above the surface. Our constraints on the wind regime provide a unique opportunity to use ground measurements from MSL to test the accuracy of winds predicted from orbital data.RAMS modeled winds in the MSL landing site

Interactions of fast molecular ions traversing thin foils. The contribution from field ionized Rydberg atoms in measurements on convoy electrons

International Nuclear Information System (INIS)

Gemmell, D.S.

1983-01-01

Experiments with fast (MeV) molecular-ion beams offer many attractive possibilities for studying atomic collisions in solids. Of particular value in such experiments is the possibility of determining the force fields (primarily in the induced electric field) that surround ionic fragments traversing a solid. One has the opportunity to evaluate these fields not just at the fragments themselves (as one would, for example, in stopping-power measurements with monatomic projectiles) but in the spatial regions extending out to several Angstroms from the fragment positions. In this paper we give a brief introduction to the subject and present some recent results

The use of a cloned bacterial gene to study mutation in mammalian cells

International Nuclear Information System (INIS)

Thacker, J.; Debenham, P.G.; Stretch, A.; Webb, M.B.T.

1983-01-01

The recombinant DNA molecule pSV2-gpt, which contains the bacterial gene coding for xanthine-guanine phosphoribosyl transferase (XGPRT) activity, was introduced into a hamster cell line lacking the equivalent mammalian enzyme (HGPRT). Hamster cell sublines were found with stable expression of XGPRT activity and were used to study mutation of the integrated pSV2-gpt DNA sequence. Mutants were selected by their resistance to 6-thioguanine (TG) under optimal conditions which were found to be very similar to those for selection of HGPRT-deficient mutants of mammalian cells. The frequency of XGPRT-deficient mutants was increased by treatment with X-rays, ethyl methanesulphonate and ethyl nitrosourea. X-Ray induction of mutants increased approximately linearly with dose up to about 500 rad, but the frequency of mutants per rad was very much higher than that usually found for 'native' mammalian genes. (orig./AJ)

Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

Science.gov (United States)

Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N; Lee, Seung-Rock

2014-01-01

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

Directory of Open Access Journals (Sweden)

Seong-Jeong Han

Full Text Available Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO, the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

A vaccine grade of yeast Saccharomyces cerevisiae expressing mammalian myostatin

Directory of Open Access Journals (Sweden)

Zhang Tingting

2012-12-01

Full Text Available Abstract Background Yeast Saccharomyces cerevisiae is a widely-used system for protein expression. We previously showed that heat-killed whole recombinant yeast vaccine expressing mammalian myostatin can modulate myostatin function in mice, resulting in increase of body weight and muscle composition in these animals. Foreign DNA introduced into yeast cells can be lost soon unless cells are continuously cultured in selection media, which usually contain antibiotics. For cost and safety concerns, it is essential to optimize conditions to produce quality food and pharmaceutical products. Results We developed a simple but effective method to engineer a yeast strain stably expressing mammalian myostatin. This method utilized high-copy-number integration of myostatin gene into the ribosomal DNA of Saccharomyces cerevisiae. In the final step, antibiotic selection marker was removed using the Cre-LoxP system to minimize any possible side-effects for animals. The resulting yeast strain can be maintained in rich culture media and stably express mammalian myostatin for two years. Oral administration of the recombinant yeast was able to induce immune response to myostatin and modulated the body weight of mice. Conclusions Establishment of such yeast strain is a step further toward transformation of yeast cells into edible vaccine to improve meat production in farm animals and treat human muscle-wasting diseases in the future.

Elabela-apelin receptor signaling pathway is functional in mammalian systems.

Science.gov (United States)

Wang, Zhi; Yu, Daozhan; Wang, Mengqiao; Wang, Qilong; Kouznetsova, Jennifer; Yang, Rongze; Qian, Kun; Wu, Wenjun; Shuldiner, Alan; Sztalryd, Carole; Zou, Minghui; Zheng, Wei; Gong, Da-Wei

2015-02-02

Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.

Host-virus interactions of mammalian endogenous retroviruses

OpenAIRE

Farkašová, Helena

2017-01-01

Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

Labeling proteins on live mammalian cells using click chemistry.

Science.gov (United States)

Nikić, Ivana; Kang, Jun Hee; Girona, Gemma Estrada; Aramburu, Iker Valle; Lemke, Edward A

2015-05-01

We describe a protocol for the rapid labeling of cell-surface proteins in living mammalian cells using click chemistry. The labeling method is based on strain-promoted alkyne-azide cycloaddition (SPAAC) and strain-promoted inverse-electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions, in which noncanonical amino acids (ncAAs) bearing ring-strained alkynes or alkenes react, respectively, with dyes containing azide or tetrazine groups. To introduce ncAAs site specifically into a protein of interest (POI), we use genetic code expansion technology. The protocol can be described as comprising two steps. In the first step, an Amber stop codon is introduced--by site-directed mutagenesis--at the desired site on the gene encoding the POI. This plasmid is then transfected into mammalian cells, along with another plasmid that encodes an aminoacyl-tRNA synthetase/tRNA (RS/tRNA) pair that is orthogonal to the host's translational machinery. In the presence of the ncAA, the orthogonal RS/tRNA pair specifically suppresses the Amber codon by incorporating the ncAA into the polypeptide chain of the POI. In the second step, the expressed POI is labeled with a suitably reactive dye derivative that is directly supplied to the growth medium. We provide a detailed protocol for using commercially available ncAAs and dyes for labeling the insulin receptor, and we discuss the optimal surface-labeling conditions and the limitations of labeling living mammalian cells. The protocol involves an initial cloning step that can take 4-7 d, followed by the described transfections and labeling reaction steps, which can take 3-4 d.

Micron-scale variations in coupled δ13C-N abundance core-rim traverses in octahedral diamonds: insights into the processes and sources of episodic diamond formation beneath the Siberian craton

NARCIS (Netherlands)

Wiggers de Vries, D.F.; Bulanova, G.; de Corte, K.; Pearson, D.G.; Davies, G.R.

2013-01-01

The internal structure and growth history of six macro-diamonds from kimberlite pipes in Yakutia (Russia) were investigated with cathodoluminescence imaging and coupled carbon isotope and nitrogen abundance analyses along detailed core to rim traverses. The diamonds are characterised by octahedral

Expression of recombinant glycoproteins in mammalian cells: towards an integrative approach to structural biology.

Science.gov (United States)

Aricescu, A Radu; Owens, Raymond J

2013-06-01

Mammalian cells are rapidly becoming the system of choice for the production of recombinant glycoproteins for structural biology applications. Their use has enabled the structural investigation of a whole new set of targets including large, multi-domain and highly glycosylated eukaryotic cell surface receptors and their supra-molecular assemblies. We summarize the technical advances that have been made in mammalian expression technology and highlight some of the structural insights that have been obtained using these methods. Looking forward, it is clear that mammalian cell expression will provide exciting and unique opportunities for an integrative approach to the structural study of proteins, especially of human origin and medically relevant, by bridging the gap between the purified state and the cellular context. Copyright © 2013 Elsevier Ltd. All rights reserved.

A validated system for ligation-free USER™ -based assembly of expression vectors for mammalian cell engineering

DEFF Research Database (Denmark)

Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Hansen, Bjarne Gram

The development in the field of mammalian cell factories require fast and high-throughput methods, this means a high need for simpler and more efficient cloning techniques. For optimization of protein expression by genetic engineering and for allowing metabolic engineering in mammalian cells, a new...

Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

Directory of Open Access Journals (Sweden)

Katherine Belov

2006-03-01

Full Text Available The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum sequence to construct the first map of a marsupial major histocompatibility complex (MHC. The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

Evolution of mammalian endothermic metabolism: leaky membranes as a source of heat

International Nuclear Information System (INIS)

Else, P.L.; Hulbert, A.J.

1987-01-01

O 2 consumption was measured at 37/degrees/C in tissue slices of liver, kidney, and brain from Amphilbolurus vitticeps and Rattus norvegicus (a reptile and mammal with same weight and body temperature) both in the presence and absence of ouabain. O 2 consumption of the mammalian tissues was two to four times that of the reptilian tissues and the mammalian tissues used three to six times the energy for Na + -K + transport than the reptilian tissues. Passive permeability to 42 K + was measured at 37/degrees/C in liver and kidney slices, and passive permeability to 22 Na + was measured at 37/degrees/C in isolated and cultured liver cells from each species. The mammalian cell membrane was severalfold leakier to both these ions than was the reptilian cell membrane, and thus the membrane pumps must use more energy to maintain the transmembrane ion gradients. It is postulated that this is a general difference between the cells of ectotherms and endotherms and thus partly explains the much higher levels of metabolism found in endothermic mammals

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

Science.gov (United States)

White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

2006-06-22

Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells

Science.gov (United States)

Ishihara, Keiichi; Yamagishi, Nobuyuki; Saito, Youhei; Takasaki, Midori; Konoshima, Takao; Hatayama, Takumi

2006-01-01

Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoter-regulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy. PMID:16817321

Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

International Nuclear Information System (INIS)

Tomita, Masanori

2010-01-01

Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

International Nuclear Information System (INIS)

Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

2014-01-01

There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

Chemical sporulation and germination: cytoprotective nanocoating of individual mammalian cells with a degradable tannic acid-FeIII complex

Science.gov (United States)

Lee, Juno; Cho, Hyeoncheol; Choi, Jinsu; Kim, Doyeon; Hong, Daewha; Park, Ji Hun; Yang, Sung Ho; Choi, Insung S.

2015-11-01

Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature.Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature. Electronic supplementary information (ESI) available: Experimental details, LSCM images, and SEM and TEM images. See DOI: 10.1039/c5nr05573c

Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT family

Directory of Open Access Journals (Sweden)

Patron Nicola

2010-05-01

Full Text Available Abstract Background In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. Results We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. Conclusions The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.

Science.gov (United States)

Richardson, Sandra R; Doucet, Aurélien J; Kopera, Huira C; Moldovan, John B; Garcia-Perez, José Luis; Moran, John V

2015-04-01

Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.

Investigation of radiation damage to biological specimens at water window wavelengths

International Nuclear Information System (INIS)

Foster, G.F.; Buckley, C.J.; Burge, R.E.; Bennett, P.M.

1992-01-01

This article reports the continuation of a series of experiments investigating the effects of soft x-ray radiation damage on the contractile elements of mammalian striated muscle (myofibrils), using their ability to contract as a functional assay. The myofibrils were exposed to 385 eV x rays. This energy is within the ''water window'' between the oxygen and carbon K edges, where the x-ray absorption coefficient of biological materials, such as protein, is about an order of magnitude greater than that for water. An exposure of 8x10 5 photons μm -1 was found to prevent contraction in the majority of myofibrils. Preliminary results indicate that it is possible to increase this exposure level by approximately 25% by adding the radioprotective dimethyl sulphoxide (DMSO), an OH radical scavenger to the myofibril buffer during irradiation. This suggests that OH radicals are important in the inactivation of myofibrils through irradiation

Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

International Nuclear Information System (INIS)

Campos-Nebel, Marcelo de; Larripa, Irene; Gonzalez-Cid, Marcela

2008-01-01

Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by γH2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU-induced DSB

Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Campos-Nebel, Marcelo de [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)], E-mail: mnebel@hematologia.anm.edu.ar; Larripa, Irene; Gonzalez-Cid, Marcela [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)

2008-11-10

Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by {gamma}H2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU

Ancient Transposable Elements Transformed the Uterine Regulatory Landscape and Transcriptome during the Evolution of Mammalian Pregnancy

Directory of Open Access Journals (Sweden)

Vincent J. Lynch

2015-02-01

Full Text Available A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs. Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.

Microdosimetric constraints on specific adaptation mechanisms to reduce DNA damage caused by ionising radiation

International Nuclear Information System (INIS)

Burkart, W.; Heusser, P.; Vijayalaxmi

1990-01-01

The protective effect of pre-exposure of lymphocytes to ionising radiation indicates the presence of 'adaptive repair' in mammalian cells. Microdosimetric considerations, however, raise some doubts on the advantage of such a cellular mechanism for specifically reducing the radiation damage caused by environmental exposures. Contrary to most chemicals which endanger the integrity of the mammalian genome, the local dose and dose rate from ionising radiation at the cellular level remain quite high, even at lowest exposures. A single electron or alpha particle passing through a cell nucleus already yields nuclear doses of up to about 3 mGy and 400 mGy, respectively. Macroscopic doses below these nuclear doses from a single event will only reduce the fraction of cell nuclei encountering the passage of a particle but not the dose or dose rate in the affected volume. At environmental doses in the range of 1 to 5 mGy per annum, the time between two consecutive hits in a specific cell nucleus is in the range of months to years. Very low concentrations of bleomycin, a drug with high affinity to DNA, also triggers an adaptive response. This points to a more general stress response mechanism which may benefit the cell even at environmental levels of radioactivity, e.g. by protecting the integrity of DNA from attacks by chemicals, by endogenous radicals, by acids from anoxia, etc. (author)

Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei

Science.gov (United States)

2010-08-01

or the early liver-stages of the mammalian life cycle . One of these antigens is the cell-traversal protein for ookinetes and sporozoites (CelTOS...Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with... Plasmodium berghei Elke S. Bergmann-Leitner1*, Ryan M. Mease1, Patricia De La Vega1, Tatyana Savranskaya2, Mark Polhemus1, Christian Ockenhouse1, Evelina

The food additive vanillic acid controls transgene expression in mammalian cells and mice.

Science.gov (United States)

Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

2012-03-01

Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

[Traditional and modern approaches to culture of preimplantation mammalian embryos in vitro].

Science.gov (United States)

Brusentsev, E Iu; Igonina, T N; Amstislavskiĭ, S Ia

2014-01-01

This review covers the basic principles and methods of in vitro culture of preimplantation mammalian embryos. The features of in vitro development of embryos of various species of animals with allowance for the composition of nutrient media are described, with special attention paid to those species that have traditionally been consideredas laboratory (i.e., mice, rats, and hamsters). The effects of suboptimal culturing conditions of preimplantation embryos on the formation of the phenotype of individuals developed from these embryos are discussed. New approaches to optimize the conditions of the development of preimplantation mammalian embryos in vitro are analyzed.

Dune and ripple migration along Curiosity's traverse in Gale Crater on Mars

Science.gov (United States)

Silvestro, S.; Vaz, D.; Ewing, R. C.; Fenton, L. K.; Michaels, T. I.; Ayoub, F.; Bridges, N. T.

2013-12-01

The NASA Mars Science Laboratory (MSL) rover, Curiosity, has safely landed near a 35-km-long dark dune field in Gale Crater on Mars. This dune field lies along Curiosity's traverse to Aeolis Mons (Mt. Sharp). Here we present new evidence of aeolian activity and further estimate wind directions within the dune field through analysis of ripple migration with the COSI-Corr technique, which provides precise measurements of ripple displacement at the sub-pixel scale.The area analyzed is located ~10 km southwest of rover Curiosity's current position and ~4 km SW of its selected path through Aeolis Mons (Mt. Sharp) (Fig. 1a). Here barchan dunes with elongated horns and seif dunes coexist with more typical barchan and dome dunes (Fig. 1a, b), with slopes sculpted by two intersecting ripple crestline orientations trending at 45° and 330°. The range of dune types and ripple orientations indicate the dune field morphology is influenced by at least two winds from the NW and the NE. The direction of migration is toward the SW, suggesting the most recent sand transporting winds were from the NE (Fig. 1c). These results match previous predictions and can be used to forecast the wind conditions close to the entry point to Mt. Sharp. Fig. 1: a-b) Study area c) Ripple migration direction computed using the COSI-Corr technique

Mammalian gamete plasma membranes re-assessments and reproductive implications

Science.gov (United States)

Establishment of the diploid status occurs with the fusion of female and male gametes. Both the mammalian oocyte and spermatozoa are haploid cells surrounded with plasma membranes that are rich in various proteins playing a crucial role during fertilization. Fertilization is a complex and ordered st...

Damage analysis: damage function development and application

International Nuclear Information System (INIS)

Simons, R.L.; Odette, G.R.

1975-01-01

The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

Unconventional Trafficking of Mammalian Phospholipase D3 to Lysosomes

Directory of Open Access Journals (Sweden)

Adriana Carolina Gonzalez

2018-01-01

Full Text Available Variants in the phospholipase D3 (PLD3 gene have genetically been linked to late-onset Alzheimer's disease. We present a detailed biochemical analysis of PLD3 and reveal its endogenous localization in endosomes and lysosomes. PLD3 reaches lysosomes as a type II transmembrane protein via a (for mammalian cells uncommon intracellular biosynthetic route that depends on the ESCRT (endosomal sorting complex required for transport machinery. PLD3 is sorted into intraluminal vesicles of multivesicular endosomes, and ESCRT-dependent sorting correlates with ubiquitination. In multivesicular endosomes, PLD3 is subjected to proteolytic cleavage, yielding a stable glycosylated luminal polypeptide and a rapidly degraded N-terminal membrane-bound fragment. This pathway closely resembles the delivery route of carboxypeptidase S to the yeast vacuole. Our experiments reveal a biosynthetic route of PLD3 involving proteolytic processing and ESCRT-dependent sorting for its delivery to lysosomes in mammalian cells.

Mammalian cycles: internally defined periods and interaction-driven amplitudes

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LR Ginzburg

2015-08-01

Full Text Available The cause of mammalian cycles—the rise and fall of populations over a predictable period of time—has remained controversial since these patterns were first observed over a century ago. In spite of extensive work on observable mammalian cycles, the field has remained divided upon what the true cause is, with a majority of opinions attributing it to either predation or to intra-species mechanisms. Here we unite the eigenperiod hypothesis, which describes an internal, maternal effect-based mechanism to explain the cycles’ periods with a recent generalization explaining the amplitude of snowshoe hare cycles in northwestern North America based on initial predator abundance. By explaining the period and the amplitude of the cycle with separate mechanisms, a unified and consistent view of the causation of cycles is reached. Based on our suggested theory, we forecast the next snowshoe hare cycle (predicted peak in 2016 to be of extraordinarily low amplitude.

The Degradome database: mammalian proteases and diseases of proteolysis.

Science.gov (United States)

Quesada, Víctor; Ordóñez, Gonzalo R; Sánchez, Luis M; Puente, Xose S; López-Otín, Carlos

2009-01-01

The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

Effects of global warming on ancient mammalian communities and their environments.

Directory of Open Access Journals (Sweden)

Larisa R G DeSantis

2009-06-01

Full Text Available Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C(3/C(4 transitions and relative seasonality.Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (approximately 1.9 million years ago and Pleistocene (approximately 1.3 million years ago in Florida. Stable isotope data demonstrate increased aridity, increased C(4 grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming.Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees N. Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems.

The Estimation Modelling of Damaged Areas by Harmful Animals

Science.gov (United States)

Jang, R.; Sung, M.; Hwang, J.; Jeon, S. W.

2017-12-01

The Republic of Korea has undergone rapid development and urban development without sufficient consideration of the environment. This type of growth is accompanied by a reduction in forest area and wildlife habitat. It is a phenomenon that affects the habitat of large mammals more than small. Especially in Korea, the damage caused by wild boar(Sus scrofa) is harsher than other large mammalian species like water deer(Hydropotes inermis), which also means that the number of these reported cases of this species is higher than ones of other mammals. Wild boar has three to eight cubs per year and it is possible to breed every year, which makes it more populous comparing with the fragmented habitats. It could be regarded as one of the top predators in Korea, which it is inevitable for humans to intervene this creature in population control. In addition, some individuals have been forced to be retreated from other habitats in major habitats, or to invade human activity areas for food activity, thereby destroying crops. Ultimately, this mammal species has been treated as farm pest animals through committing road kills and urban emergences. In this study, we has estimated possible farm pest animal present points from the damage district using 2,505 hazardous wildlife damage areas with four types of geological informations, four kinds of forest information, land cover, and distribution of farmland occurred in Gyeongnam province in Korea. In the estimating model, utilizing MAXENT, information of background point was set to 10,000, 70% of the damaged sites were used to construct the model, 30% was used for verification, and 10 times of crossvalidate were proceeded - verified by AUC of ROC. As a result of analyses, AUC was 0.847, and the percent contribution of the forest information was the distance toward inner-forest areas, 36.1%, the land cover, 16.5%, the distance from the field, 14.9%. Furthermore, the permutation importance was 24.9% of the cover, 12.3% of the height

Effect of temperature on spontaneous release of transmitter at the mammalian neuromuscular junction

Energy Technology Data Exchange (ETDEWEB)

Duncan, C J; Statham, H E

1977-01-01

Temperature has a multifactorial effect on miniature endplate potential (MEPP) frequency at the mammalian neuromuscular junction, with a negative Q/sub 10/ at 14--28/sup 0/C. The results are explained in terms of the effect of temperature on the various factors that control (Ca/sup 2/+sub i/ at the presynaptic terminals. The temperature-sensitivity of the Ca/sup 2 +/-transport enzyme is believed to be of particular significance and accounts for the observed differences between the amphibian and mammalian neuromuscular junctions.

Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE

OpenAIRE

Rella, Monika; Elliot, Joann L; Revett, Timothy J; Lanfear, Jerry; Phelan, Anne; Jackson, Richard M; Turner, Anthony J; Hooper, Nigel M

2007-01-01

Abstract Background Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple ...

Hyperthermal (1-100 eV) nitrogen ion scattering damage to D-ribose and 2-deoxy-D-ribose films.

Science.gov (United States)

Deng, Zongwu; Bald, Ilko; Illenberger, Eugen; Huels, Michael A

2007-10-14

Highly charged heavy ion traversal of a biological medium can produce energetic secondary fragment ions. These fragment ions can in turn cause collisional and reactive scattering damage to DNA. Here we report hyperthermal (1-100 eV) scattering of one such fragment ion (N(+)) from biologically relevant sugar molecules D-ribose and 2-deoxy-D-ribose condensed on polycrystalline Pt substrate. The results indicate that N(+) ion scattering at kinetic energies down to 10 eV induces effective decomposition of both sugar molecules and leads to the desorption of abundant cation and anion fragments. Use of isotope-labeled molecules (5-(13)C D-ribose and 1-D D-ribose) partly reveals some site specificity of the fragment origin. Several scattering reactions are also observed. Both ionic and neutral nitrogen atoms abstract carbon from the molecules to form CN(-) anion at energies down to approximately 5 eV. N(+) ions also abstract hydrogen from hydroxyl groups of the molecules to form NH(-) and NH(2) (-) anions. A fraction of OO(-) fragments abstract hydrogen to form OH(-). The formation of H(3)O(+) ions also involves hydrogen abstraction as well as intramolecular proton transfer. These findings suggest a variety of severe damaging pathways to DNA molecules which occur on the picosecond time scale following heavy ion irradiation of a cell, and prior to the late diffusion-limited homogeneous chemical processes.

Integrated enhanced bioremediation and vacuum extraction for remediation of a hydrocarbon release in response to oscillating hydrologic conditions 'Traverse Co-Bio-Vac'

International Nuclear Information System (INIS)

Korreck, W.M.; Armstrong, J.M.; Douglass, R.H.

1992-01-01

The use of enhanced in-situ biological treatment and vacuum extraction has been demonstrated to be successful in the remediation of ground water and soil contaminated with hydrocarbons. Seasonal fluctuations in the ground water causes the zone of contamination to be in the either saturated or unsaturated zone of the aquifer. In order to address these conditions, an integrated engineering design approach is being taken for the full scale remediation of an aviation of an aviation gasoline spill at the US Coast Guard Air Station at Traverse City, Township, Michigan. Enhanced aerobic biodegradation will be utilized during the periods of high water table whereby most of the contaminated interval is saturated. Carbon treated water will be utilized from the existing ground water plume. Oxygen will be injected via an oxygen generator to saturate the process stream prior to discharge to the aquifer. During low water table conditions, the same infrastructure will be utilized as a modified vacuum extraction system. The same injection wells used during the high water table would then be used during the low table condition as vapor extraction wells. The vapors will be routed to an above-ground catalytic incinerator for compound destruction. This integrated approach, entitled 'Traverse Co-Bio-Vac,' should reduce the capital costs of installing a full scale remedial system as well allowing the system to operate efficiently depending on water table conditions. The system is expected to be constructed in 1992

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins.

Science.gov (United States)

Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M; Ballard, Grant; Ainley, David G; Varsani, Arvind

2017-07-01

The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds ( n  = 5), a fish ( n  = 1), a snake ( n  = 1), and turtles ( n  = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin ( Pygoscelis adeliae ) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota , associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis ), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins

Science.gov (United States)

Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M.; Ballard, Grant; Ainley, David G.; Varsani, Arvind

2017-01-01

The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds (n = 5), a fish (n = 1), a snake (n = 1), and turtles (n = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin (Pygoscelis adeliae) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota, associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We estimated the

Replicative bypass repair of ultraviolet damage to DNA of mammalian cells: caffeine sensitive and caffeine resistant mechanism

International Nuclear Information System (INIS)

Fujiwara, Y.; Tatsumi, M.

1976-01-01

Replicative bypass repair of UV damage to DNA was studied in a wide variaty of human, mouse and hamster cells in culture. Survival curve analysis revealed that in established cell lines (mouse L, Chinese hamster V79, HeLa S3 and SV40-transformed xeroderma pigmentosum (XP), post-UV caffeine treatment potentiated cell killing by reducing the extrapolation number and mean lethal UV fluence (Do). In the Do reduction as the result of random inactivation by caffeine of sensitive repair there were marked clonal differences among such cell lines, V79 being most sensitive to caffeine potentiation. However, other diploid cell lines (normal human, excision-defective XP and Syrian hamster) exhibited no obvious reduction in Do by caffeine. In parallel, alkaline sucrose sedimentation results showed that the conversion of initially smaller segments of DNA synthesized after irradiation with 10 J/m 2 to high-molecular-weight DNA was inhibited by caffeine in transformed XP cells, but not in the diploid human cell lines. Exceptionally, diploid XP variants had a retarded ability of bypass repair which was drastically prevented by caffeine, so that caffeine enhanced the lethal effect of UV. Neutral CsCl study on the bypass repair mechanism by use of bromodeoxyuridine for DNA synthesis on damaged template suggests that the pyrimodine dimer acts as a block to replication and subsequently it is circumvented presumably by a new process involving replicative bypassing following strand displacement, rather than by gap-filling de novo. This mechanism worked similarly in normal and XP cells, whether or not caffeine was present, indicating that excision of dimer is not always necessary. However, replicative bypassing became defective in XP variant and transformed XP cells when caffeine was present. It appears, therefore, that the replicative bypass repair process is either caffeine resistant or sensitive, depending on the cell type used, but not necessarily on the excision repair capability

Damage and repair of irradiated mammalian brain

International Nuclear Information System (INIS)

Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.

1989-07-01

We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as ''vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs

Damage and repair of irradiated mammalian brain

Energy Technology Data Exchange (ETDEWEB)

Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K. (Lawrence Berkeley Lab., CA (USA); Stanford Univ., CA (USA). Medical Center; Brookside Hospital, San Pablo, CA (USA))

1989-07-01

We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

Engineered mammalian cells for production of recombinant proteins

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to mammalian cells modified to provide for improved expression of a recombinant protein of interest. In particular, the invention relates to CHO cells and other host cells in which the expression of one or more endogenous secreted proteins has been disrupted, as well...... as to the preparation, identification and use of such cells in the production of recombinant proteins....

Functional noncoding sequences derived from SINEs in the mammalian genome.

Science.gov (United States)

Nishihara, Hidenori; Smit, Arian F A; Okada, Norihiro

2006-07-01

Recent comparative analyses of mammalian sequences have revealed that a large number of nonprotein-coding genomic regions are under strong selective constraint. Here, we report that some of these loci have been derived from a newly defined family of ancient SINEs (short interspersed repetitive elements). This is a surprising result, as SINEs and other transposable elements are commonly thought to be genomic parasites. We named the ancient SINE family AmnSINE1, for Amniota SINE1, because we found it to be present in mammals as well as in birds, and some copies predate the mammalian-bird split 310 million years ago (Mya). AmnSINE1 has a chimeric structure of a 5S rRNA and a tRNA-derived SINE, and is related to five tRNA-derived SINE families that we characterized here in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. All of the newly described SINE families have a common central domain that is also shared by zebrafish SINE3, and we collectively name them the DeuSINE (Deuterostomia SINE) superfamily. Notably, of the approximately 1000 still identifiable copies of AmnSINE1 in the human genome, 105 correspond to loci phylogenetically highly conserved among mammalian orthologs. The conservation is strongest over the central domain. Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of the copies have acquired genomic functionality.

Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

Science.gov (United States)

Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

2016-11-04

Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

Introducing Mammalian Cell Culture and Cell Viability Techniques in the Undergraduate Biology Laboratory.

Science.gov (United States)

Bowey-Dellinger, Kristen; Dixon, Luke; Ackerman, Kristin; Vigueira, Cynthia; Suh, Yewseok K; Lyda, Todd; Sapp, Kelli; Grider, Michael; Crater, Dinene; Russell, Travis; Elias, Michael; Coffield, V McNeil; Segarra, Verónica A

2017-01-01

Undergraduate students learn about mammalian cell culture applications in introductory biology courses. However, laboratory modules are rarely designed to provide hands-on experience with mammalian cells or teach cell culture techniques, such as trypsinization and cell counting. Students are more likely to learn about cell culture using bacteria or yeast, as they are typically easier to grow, culture, and manipulate given the equipment, tools, and environment of most undergraduate biology laboratories. In contrast, the utilization of mammalian cells requires a dedicated biological safety cabinet and rigorous antiseptic techniques. For this reason, we have devised a laboratory module and method herein that familiarizes students with common cell culture procedures, without the use of a sterile hood or large cell culture facility. Students design and perform a time-efficient inquiry-based cell viability experiment using HeLa cells and tools that are readily available in an undergraduate biology laboratory. Students will become familiar with common techniques such as trypsinizing cells, cell counting with a hemocytometer, performing serial dilutions, and determining cell viability using trypan blue dye. Additionally, students will work with graphing software to analyze their data and think critically about the mechanism of death on a cellular level. Two different adaptations of this inquiry-based lab are presented-one for non-biology majors and one for biology majors. Overall, these laboratories aim to expose students to mammalian cell culture and basic techniques and help them to conceptualize their application in scientific research.

TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

Science.gov (United States)

Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

2014-01-24

Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

BSp66 protease is widespread in the acrosomal region of sperm from several mammalian species

International Nuclear Information System (INIS)

Cesari, A.; Katunar, M.R.; Monclus, M.A.; Vincenti, A.; Fornes, M.W.

2004-01-01

Fertilization in mammals comprises a sequence of events leading to the fusion of sperm and oocyte membranes. Although proteases are known to be involved in this process, their role in fertilization is controversial. There is extensive work on the characterization of proteolytic systems, including serine proteases, which demonstrates that acrosomal proteases can be distinguished among the sperm of different mammalian species on the basis of the gelatin-hydrolyzing activity on SDS-PAGE by the quantity and variety of the enzymes. In this report, we investigated the occurrence and activity of the serine protease BSp66, previously characterized in bovine spermatozoa, in various mammalian sperm. A protein with a molecular mass of 66 kDa cross-reacted with heterologous antibodies against bovine BSp66 when sperm extracts of several mammalian species were analyzed by Western blot. In agreement, proteolytic activity corresponding to the molecular mass of BSp66 was detected by gelatin zymography in all the species analyzed. This protein was located on the acrosomal region of sperm cells by immunofluorescence methods. We concluded that BSp66 is widespread in mammalian sperm, with a conserved location in the acrosomal region

Cellular and Chemical Neuroscience of Mammalian Sleep

OpenAIRE

Datta, Subimal

2010-01-01

Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

Energy Technology Data Exchange (ETDEWEB)

Gehrau, Ricardo C.; D' Astolfo, Diego S.; Andreoli, Veronica [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Bocco, Jose L., E-mail: jbocco@fcq.unc.edu.ar [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Koritschoner, Nicolas P. [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

2011-02-10

The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC{sub 50}). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p < 0.0001) in KLF6 mRNA levels were observed depending on the cellular p53 status upon cell damage. KLF6 expression was significantly increased in 63% of p53-deficient cells (122/195). Conversely, KLF6 mRNA level decreased nearly 4 fold in more than 70% of p53+/+ cells. In addition, klf6 gene promoter activity was down-regulated by DNA damaging agents in cells expressing the functional p53 protein whereas it was moderately increased in the absence of functional p53. Consistent results were obtained for the endogenous KLF6 protein level. Results indicate that human klf6 gene expression is responsive to external cell damage mediated by IC{sub 50} concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable

The insecticide buprofezin induces morphological transformation and kinetochore-positive micronuclei in cultured Syrian hamster embryo cells in the absence of detectable DNA damage.

Science.gov (United States)

Herrera, L A; Ostrosky-Wegman, P; Schiffmann, D; Chen, Q Y; Ziegler-Skylakakis, K; Andrae, U

1993-11-01

The insecticide buprofezin was examined for its genotoxicity in cultured Syrian hamster embryo cells in order to better understand the mechanisms underlying the genotoxicity of the compound in mammalian cells. Exposure to buprofezin concentrations of 12.5-100 microM did not significantly affect the colony-forming ability of the cells, but did result in increased frequencies of morphologically transformed colonies. Treatment with buprofezin did not cause a detectable induction of DNA repair synthesis, an indicator of DNA damage, but significantly increased the frequency of micronuclei. Immunostaining of the cells with antikinetochore antibody (CREST antibody) showed that essentially all of the buprofezin-induced micronuclei were kinetochore-positive. The results suggest that morphological transformation of Syrian hamster embryo cells by buprofezin results from an interaction of the compound or a metabolite of it with the mitotic apparatus rather than from DNA damage.

The Yersinia pseudotuberculosis and Yersinia pestis toxin complex is active against cultured mammalian cells.

Science.gov (United States)

Hares, Michelle C; Hinchliffe, Stewart J; Strong, Philippa C R; Eleftherianos, Ioannis; Dowling, Andrea J; ffrench-Constant, Richard H; Waterfield, Nick

2008-11-01

The toxin complex (Tc) genes were first identified in the insect pathogen Photorhabdus luminescens and encode approximately 1 MDa protein complexes which are toxic to insect pests. Subsequent genome sequencing projects have revealed the presence of tc orthologues in a range of bacterial pathogens known to be associated with insects. Interestingly, members of the mammalian-pathogenic yersiniae have also been shown to encode Tc orthologues. Studies in Yersinia enterocolitica have shown that divergent tc loci either encode insect-active toxins or play a role in colonization of the gut in gastroenteritis models of rats. So far little is known about the activity of the Tc proteins in the other mammalian-pathogenic yersiniae. Here we present work to suggest that Tc proteins in Yersinia pseudotuberculosis and Yersinia pestis are not insecticidal toxins but have evolved for mammalian pathogenicity. We show that Tc is secreted by Y. pseudotuberculosis strain IP32953 during growth in media at 28 degrees C and 37 degrees C. We also demonstrate that oral toxicity of strain IP32953 to Manduca sexta larvae is not due to Tc expression and that lysates of Escherichia coli BL21 expressing the Yersinia Tc proteins are not toxic to Sf9 insect cells but are toxic to cultured mammalian cell lines. Cell lysates of E. coli BL21 expressing the Y. pseudotuberculosis Tc proteins caused actin ruffles, vacuoles and multi-nucleation in cultured human gut cells (Caco-2); similar morphology was observed after application of a lysate of E. coli BL21 expressing the Y. pestis Tc proteins to mouse fibroblast NIH3T3 cells, but not Caco-2 cells. Finally, transient expression of the individual Tc proteins in Caco-2 and NIH3T3 cell lines reproduced the actin and nuclear rearrangement observed with the topical applications. Together these results add weight to the growing hypothesis that the Tc proteins in Y. pseudotuberculosis and Y. pestis have been adapted for mammalian pathogenicity. We further

A platform for rapid prototyping of synthetic gene networks in mammalian cells

Science.gov (United States)

Duportet, Xavier; Wroblewska, Liliana; Guye, Patrick; Li, Yinqing; Eyquem, Justin; Rieders, Julianne; Rimchala, Tharathorn; Batt, Gregory; Weiss, Ron

2014-01-01

Mammalian synthetic biology may provide novel therapeutic strategies, help decipher new paths for drug discovery and facilitate synthesis of valuable molecules. Yet, our capacity to genetically program cells is currently hampered by the lack of efficient approaches to streamline the design, construction and screening of synthetic gene networks. To address this problem, here we present a framework for modular and combinatorial assembly of functional (multi)gene expression vectors and their efficient and specific targeted integration into a well-defined chromosomal context in mammalian cells. We demonstrate the potential of this framework by assembling and integrating different functional mammalian regulatory networks including the largest gene circuit built and chromosomally integrated to date (6 transcription units, 27kb) encoding an inducible memory device. Using a library of 18 different circuits as a proof of concept, we also demonstrate that our method enables one-pot/single-flask chromosomal integration and screening of circuit libraries. This rapid and powerful prototyping platform is well suited for comparative studies of genetic regulatory elements, genes and multi-gene circuits as well as facile development of libraries of isogenic engineered cell lines. PMID:25378321

Regulation of Autophagy by Glucose in Mammalian Cells

Directory of Open Access Journals (Sweden)

Erwin Knecht

2012-07-01

Full Text Available Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role.

EMMA: An Extensible Mammalian Modular Assembly Toolkit for the Rapid Design and Production of Diverse Expression Vectors.

Science.gov (United States)

Martella, Andrea; Matjusaitis, Mantas; Auxillos, Jamie; Pollard, Steven M; Cai, Yizhi

2017-07-21

Mammalian plasmid expression vectors are critical reagents underpinning many facets of research across biology, biomedical research, and the biotechnology industry. Traditional cloning methods often require laborious manual design and assembly of plasmids using tailored sequential cloning steps. This process can be protracted, complicated, expensive, and error-prone. New tools and strategies that facilitate the efficient design and production of bespoke vectors would help relieve a current bottleneck for researchers. To address this, we have developed an extensible mammalian modular assembly kit (EMMA). This enables rapid and efficient modular assembly of mammalian expression vectors in a one-tube, one-step golden-gate cloning reaction, using a standardized library of compatible genetic parts. The high modularity, flexibility, and extensibility of EMMA provide a simple method for the production of functionally diverse mammalian expression vectors. We demonstrate the value of this toolkit by constructing and validating a range of representative vectors, such as transient and stable expression vectors (transposon based vectors), targeting vectors, inducible systems, polycistronic expression cassettes, fusion proteins, and fluorescent reporters. The method also supports simple assembly combinatorial libraries and hierarchical assembly for production of larger multigenetic cargos. In summary, EMMA is compatible with automated production, and novel genetic parts can be easily incorporated, providing new opportunities for mammalian synthetic biology.

Replication of chromosomal and episomal DNA in X-ray-damaged human cells: A cis- or trans-acting mechanism

International Nuclear Information System (INIS)

Cleaver, J.E.; Rose, R.; Mitchell, D.L.

1990-01-01

Episomal plasmids and viruses in mammalian cells present small targets for X-ray-induced DNA damage. At doses up to 100 Gy, DNA strand breaks or endonuclease III-sensitive sites were not discernible in 10.3-kb Epstein-Barr virus-based plasmid DNA or in 4.9-kb defective simian virus 40 DNA. DNA replication in these small molecules, however, was inhibited strongly by X-ray doses of greater than or equal to 20 Gy, decreasing to only 20 to 40% of control values. Inhibition was relieved slightly by growth in caffeine but was increased by growth in 3-aminobenzamide. Inhibition of DNA replication in episomal DNA molecules that are too small to sustain significant damage directly to their DNA may be due to either (a) a trans-acting diffusible factor that transfers the consequences of DNA breakage to episomes and to other replicating molecules, (b) a cis-acting mechanism in which episomes are structurally linked to genomic chromatin, and replication of both episomal and chromosomal replicons is under common control, or (c) radiation damage on other cellular structures unrelated to DNA. The resolution of these cellular mechanisms may shed light on the X-ray-resistant replication in ataxia-telangiectasia and may suggest strategies for molecular characterization of potential trans- or cis-acting factors

Identifying Time Measurement Tampering in the Traversal Time and Hop Count Analysis (TTHCA Wormhole Detection Algorithm

Directory of Open Access Journals (Sweden)

Jonny Karlsson

2013-05-01

Full Text Available Traversal time and hop count analysis (TTHCA is a recent wormhole detection algorithm for mobile ad hoc networks (MANET which provides enhanced detection performance against all wormhole attack variants and network types. TTHCA involves each node measuring the processing time of routing packets during the route discovery process and then delivering the measurements to the source node. In a participation mode (PM wormhole where malicious nodes appear in the routing tables as legitimate nodes, the time measurements can potentially be altered so preventing TTHCA from successfully detecting the wormhole. This paper analyses the prevailing conditions for time tampering attacks to succeed for PM wormholes, before introducing an extension to the TTHCA detection algorithm called ∆T Vector which is designed to identify time tampering, while preserving low false positive rates. Simulation results confirm that the ∆T Vector extension is able to effectively detect time tampering attacks, thereby providing an important security enhancement to the TTHCA algorithm.

Traversable Lorentzian wormholes in the vacuum low energy effective string theory in Einstein and Jordan frames

International Nuclear Information System (INIS)

Nandi, K.K.; Zhang Yuanzhong

2004-01-01

Three new classes (II-IV) of solutions of the vacuum low energy effective string theory in four dimensions are derived. Wormhole solutions are investigated in those solutions including the class I case both in the Einstein and in the Jordan (string) frame. It turns out that, of the eight classes of solutions investigated (four in the Einstein frame and four in the corresponding string frame), massive Lorentzian traversable wormholes exist in five classes. Nontrivial massless limit exists only in class I Einstein frame solution while none at all exists in the string frame. An investigation of test scalar charge motion in the class I solution in the two frames is carried out by using the Plebanski-Sawicki theorem. A curious consequence is that the motion around the extremal zero (Keplerian) mass configuration leads, as a result of scalar-scalar interaction, to a new hypothetical 'mass' that confines test scalar charges in bound orbits, but does not interact with neutral test particles

Focusing on RISC assembly in mammalian cells.

Science.gov (United States)

Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

2008-04-11

RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

Focusing on RISC assembly in mammalian cells

International Nuclear Information System (INIS)

Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

2008-01-01

RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

Mammalian Gravity Receptors: Structure and Metabolism

Science.gov (United States)

Ross, M. D.

1985-01-01

Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

International Nuclear Information System (INIS)

Grollman, A.P.; Takeshita, Masaru

1995-01-01

More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura's discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10 5 guanine residues in mammalian DNA are oxidized at the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA

Signal Peptide and Denaturing Temperature are Critical Factors for Efficient Mammalian Expression and Immunoblotting of Cannabinoid Receptors*

Science.gov (United States)

WANG, Chenyun; WANG, Yingying; WANG, Miao; CHEN, Jiankui; YU, Nong; SONG, Shiping; KAMINSKI, Norbert E.; ZHANG, Wei

2013-01-01

Summary Many researchers employed mammalian expression system to artificially express cannabinoid receptors, but immunoblot data that directly prove efficient protein expression can hardly be seen in related research reports. In present study, we demonstrated cannabinoid receptor protein was not able to be properly expressed with routine mammalian expression system. This inefficient expression was rescued by endowing an exogenous signal peptide ahead of cannabinoid receptor peptide. In addition, the artificially synthesized cannabinoid receptor was found to aggregate under routine sample denaturing temperatures (i.e., ≥95°C), forming a large molecular weight band when analyzed by immunoblotting. Only denaturing temperatures ≤75°C yielded a clear band at the predicted molecular weight. Collectively, we showed that efficient mammalian expression of cannabinoid receptors need a signal peptide sequence, and described the requirement for a low sample denaturing temperature in immunoblot analysis. These findings provide very useful information for efficient mammalian expression and immunoblotting of membrane receptors. PMID:22528237

Incorporation of nanoparticles within mammalian spermatozoa using in vitro capacitation

Science.gov (United States)

There is still much unknown about the journey of spermatozoa within the female genital tract. Recent studies have investigated mammalian spermatozoa labeling with fluorescent quantum dot nanoparticles (QD) for non-invasive imaging. Furthermore, the incorporation of these QD within the spermatozoa ma...

Intracellular dielectric tagging for improved optical manipulation of mammalian cells

CSIR Research Space (South Africa)

Mthunzi, P

2010-05-01

Full Text Available review the application of optical forces for cellmanipulation and sorting, highlighting some of the key experiments over the last twenty years.We then introduce a new technique for enhancing the dielectric contrast of mammalian cells, which is a result...

Stability of resazurin in buffers and mammalian cell culture media

DEFF Research Database (Denmark)

Rasmussen, Eva; Nicolaisen, G.M.

1999-01-01

The utility of a ferricyanide/ferrocyanide system used in the AlamarBlue(TM) (Serotec, Oxford, UK) vital. dye to inhibit the reduction of resazurin by mammalian cell culture media is questioned. Resazurin was found to be relatively stable when dissolved in phosphate-buffered saline (PBS). The use...... of HEPES resulted in a huge immediate dye reduction, which was significantly enhanced by exposure to diffuse light from fluorescent tubes in the laboratory 8 h per day. The reduction of resazurin by various cell culture media was time and temperature dependent, and it was significantly enhanced......'s nutrient mixture F-10 and F-12. Fetal calf serum (5-20%) slightly decreased resazurin reduction during the first 2 days of incubation. The reduction of resazurin by mammalian cell culture media do not appear to be problematic under normal culture conditions, and it is primarily dependent upon the presence...

Mammalian sleep

Science.gov (United States)

Staunton, Hugh

2005-05-01

This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

Damage detection in high-rise buildings using damage-induced rotations

International Nuclear Information System (INIS)

Sung, Seung Hun; Jung, Ho Youn; Lee, Jung Hoon; Jung, Hyung Jo

2016-01-01

In this paper, a new damage-detection method based on structural vibration is proposed. The essence of the proposed method is the detection of abrupt changes in rotation. Damage-induced rotation (DIR), which is determined from the modal flexibility of the structure, initially occurs only at a specific damaged location. Therefore, damage can be localized by evaluating abrupt changes in rotation. We conducted numerical simulations of two damage scenarios using a 10-story cantilever-type building model. Measurement noise was also considered in the simulation. We compared the sensitivity of the proposed method to localize damage to that of two conventional modal-flexibility-based damage-detection methods, i.e., uniform load surface (ULS) and ULS curvature. The proposed method was able to localize damage in both damage scenarios for cantilever structures, but the conventional methods could not

Damage detection in high-rise buildings using damage-induced rotations

International Nuclear Information System (INIS)

Sung, Seung Hoon; Jung, Ho Youn; Lee, Jung Hoon; Jung, Hyung Jo

2014-01-01

In this paper, a new damage-detection method based on structural vibration is proposed. The essence of the proposed method is the detection of abrupt changes in rotation. Damage-induced rotation (DIR), which is determined from the modal flexibility of the structure, initially occurs only at a specific damaged location. Therefore, damage can be localized by evaluating abrupt changes in rotation. We conducted numerical simulations of two damage scenarios using a 10-story cantilever-type building model. Measurement noise was also considered in the simulation. We compared the sensitivity of the proposed method to localize damage to that of two conventional modal-flexibility-based damage-detection methods, i.e., uniform load surface (ULS) and ULS curvature. The proposed method was able to localize damage in both damage scenarios for cantilever structures, but the conventional methods could not.

Mammalian Herbivores in the Boreal Forests: Their Numerical Fluctuations and Use by Man

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Kjell Danell

1998-12-01

Full Text Available Within the boreal zone, there are about 50 native mammalian herbivore species that belong to the orders Artiodactyla, Rodentia, and Lagomorpha. Of these species, 31 occur in the Nearctic and 24 in the Palaearctic. Only six species occur in both regions. Species of the family Cervidae have probably been, and still are, the most important group for man, as they provide both meat and hides. Pelts from squirrels, muskrats, and hares were commercially harvested at the beginning of the century, but have less value today. The semi-domestic reindeer in the Palaearctic produces meat and hides on a commercial basis. It is also used for milking, to a limited extent, as is the semi-domestic moose in Russia. The Siberian musk deer is used for its musk and is raised in captivity in China. All species heavier than 1 kg are utilized by man, those with a body mass in the range 1 kg - 1 hg are sometimes used, and species lighter than 1 hg are rarely used. Here, we review the numerical fluctuations in terms of periodicity and amplitude, based on an extensive data set found in the literature, especially from the former Soviet Union. Current understanding of the underlying factors behind the population fluctuations is briefly reviewed. Management and conservation aspects of the mammalian herbivores in the boreal zone are also discussed. We conclude that there is a challenge to manage the forests for the mammalian herbivores, but there is also a challenge to manage the populations of mammalian herbivores for the forests.

Mammalian collection on Noah's Ark: the effects of beauty, brain and body size.

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Daniel Frynta

Full Text Available The importance of today's zoological gardens as the so-called "Noah's Ark" grows as the natural habitat of many species quickly diminishes. Their potential to shelter a large amount of individuals from many species gives us the opportunity to reintroduce a species that disappeared in nature. However, the selection of animals to be kept in zoos worldwide is highly selective and depends on human decisions driven by both ecological criteria such as population size or vulnerability and audience-driven criteria such as aesthetic preferences. Thus we focused our study on the most commonly kept and bred animal class, the mammals, and we asked which factors affect various aspects of the mammalian collection of zoos. We analyzed the presence/absence, population size, and frequency per species of each of the 123 mammalian families kept in the worldwide zoo collection. Our aim was to explain these data using the human-perceived attractiveness of mammalian families, their body weight, relative brain size and species richness of the family. In agreement with various previous studies, we found that the body size and the attractiveness of mammals significantly affect all studied components of the mammalian collection of zoos. There is a higher probability of the large and attractive families to be kept. Once kept, these animals are presented in larger numbers in more zoos. On the contrary, the relative mean brain size only affects the primary selection whether to keep the family or not. It does not affect the zoo population size or the number of zoos that keep the family.

Multiplexed expression and screening for recombinant protein production in mammalian cells

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McCafferty John

2006-12-01

Full Text Available Abstract Background A variety of approaches to understanding protein structure and function require production of recombinant protein. Mammalian based expression systems have advantages over bacterial systems for certain classes of protein but can be slower and more laborious. Thus the availability of a simple system for production and rapid screening of constructs or conditions for mammalian expression would be of great benefit. To this end we have coupled an efficient recombinant protein production system based on transient transfection in HEK-293 EBNA1 (HEK-293E suspension cells with a dot blot method allowing pre-screening of proteins expressed in cells in a high throughput manner. Results A nested PCR approach was used to clone 21 extracellular domains of mouse receptors as CD4 fusions within a mammalian GATEWAY expression vector system. Following transient transfection, HEK-293E cells grown in 2 ml cultures in 24-deep well blocks showed similar growth kinetics, viability and recombinant protein expression profiles, to those grown in 50 ml shake flask cultures as judged by western blotting. Following optimisation, fluorescent dot blot analysis of transfection supernatants was shown to be a rapid method for analysing protein expression yielding similar results as western blot analysis. Addition of urea enhanced the binding of glycoproteins to a nitrocellulose membrane. A good correlation was observed between the results of a plate based small scale transient transfection dot blot pre-screen and successful purification of proteins expressed at the 50 ml scale. Conclusion The combination of small scale multi-well plate culture and dot blotting described here will allow the multiplex analysis of different mammalian expression experiments enabling a faster identification of high yield expression constructs or conditions prior to large scale protein production. The methods for parallel GATEWAY cloning and expression of multiple constructs in cell

Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index

DEFF Research Database (Denmark)

Suppiah, Ravi; Flossman, Oliver; Mukhtyar, Chetan

2011-01-01

To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis.......To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis....

Assessing the accuracy of software predictions of mammalian and microbial metabolites

Science.gov (United States)

New chemical development and hazard assessments benefit from accurate predictions of mammalian and microbial metabolites. Fourteen biotransformation libraries encoded in eight software packages that predict metabolite structures were assessed for their sensitivity (proportion of ...

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

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Yang Li

Full Text Available Voltage-gated sodium (Nav channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions, a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.